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Transfusion 
Medicine 
Handbook 
Third Edition, 
2016
A Guide to the Clinical Use 
of Blood Components, 
Blood Products and Blood 
Transfusion Procedures in  
New Zealand

NEW ZEALAND BLOOD SERVICE
New Zealand Blood Service (NZBS) was formed in 1998 integrating all hospital-based 
transfusion services into a single national organisation. Since 2001, NZBS has managed 
the recruitment of blood donors, and the collection, processing and accreditation of 
all donated blood. This ensures that the demand for blood components used in the 
treatment of patients in all public and private hospitals is met. 
As well as the collection of blood from donors at many fixed and mobile sites throughout 
the country, a wide range of activities are carried out at the main centres. These include 
recruitment of donors for high titre immune plasma (anti-D, tetanus, hepatitis B and 
zoster immunoglobulin), recruitment of apheresis donors predominantly for plasma 
and platelets but also granulocytes, and collection of haemopoietic progenitor cells. 
NZBS also carries out therapeutic plasma exchange, therapeutic venesection and 
collection of autologous blood.
Other functions of NZBS include specialist immunohaematology, tissue typing 
for transplantation, skin and bone banking, production of serum eye drops and 
cryogenic storage of blood components. The national stock of rare blood, national 
immunohaematology Reference Laboratory, national Tissue Typing Laboratory and the 
New Zealand Bone Marrow Donor Registry are all located at the NZBS Auckland centre. 
NZBS is responsible for the collection and coordination of plasma supply to CSL 
Behring in Melbourne where New Zealand plasma is fractionated into plasma products, 
which NZBS then distributes to hospitals and health professionals.
NZBS maintains close liaison with public and private hospitals, general practitioners 
and midwives. Hospital transfusion committees operate in most major hospitals and 
NZBS is involved with these in an advisory capacity. 
NZBS manages the blood banks in six of the country’s major hospitals, with the 
remainder being managed by the District Health Boards (DHBs) or local community 
laboratory providers. The blood banks carry out various activities including the final 
compatibility checking and issuing of blood components and plasma products for 
transfusion. 
A national computer system, eProgesa, links NZBS and all the main hospital blood 
banks. eProgesa manages the whole transfusion process with full traceability of each 
individual blood component from donation to its final fate. Information from eProgesa 
allows NZBS to monitor blood component usage and, together with the DHBs, 
actively manage demand.
There are many elements to the transfusion process that need to be managed 
effectively to ensure blood components are used appropriately, and the relationship 
between NZBS and the DHBs is a key part of this. NZBS undertakes audits of clinical 
transfusion practice and blood use, monitors transfusion-related adverse events 
through a national Haemovigilance programme and provides a wide range of clinical, 
nursing and technical oversight and support. 
Transfusion Medicine Handbook 3rd Edition 
Page 1

CONTENTS 
PAGE
1. INTRODUCTION 
12
  1.1 Audience 
12
  1.2 Evidence 
12
 
1.3  Clinical practice guidelines 
12
  1.4 Haemovigilance 
13
2.  COLLECTION, TESTING AND PROCESSING OF BLOOD DONATIONS  15
 
2.1  Blood donors 
15
 
2.2  Donor selection criteria 
15
 
2.3  Self-sufficiency and the volunteer status of donors 
16
 
2.4  Informed consent for donation 
16
 
2.5  Apheresis donation 
16
 
2.6  Directed and selected donation 
17
  2.7 Haemochromatosis 
17
 
2.8  Cord blood donation 
17
 
2.9  Testing of donor blood 
18
 
2.10 Leucodepletion 
18
 
2.11  Processing of collected blood to components 
19
 
2.12  Processing of collected blood to fractionated products 
19
 
2.13  Blood components and fractionated products as medicines 
20
3.  GUIDE TO GOOD TRANSFUSION PRACTICE 
21
 
3.1  Clinical governance 
21
 
3.2  Prescribing blood components and fractionated products 
22
 
3.3  Informed consent to receive a transfusion 
23
 
3.4  Requesting blood components and fractionated products 
23
 
3.5  Blood stock management: the maximum blood order schedule 
24
 
3.6  Collecting blood samples for pretransfusion testing 
24
 
3.7  Pretransfusion testing 
25
 
3.8  Patients with a positive antibody screen 
26
 
3.9  Sample validity (‘72-hour rule’) 
26
 
3.10  Provision of red cells in an emergency 
27
 
3.11  Removal from storage and time limits for infusion 
28
 
3.12  Administration and observation of transfusion 
29
 
3.13  Rate of infusion and precautions 
29
 
3.14  Infusion pumps 
30
 
3.15  Blood administration sets and filters 
30
 
3.16  Warming of blood products 
30
 
3.17  Compatible intravenous solutions 
31
 
3.18  Adding medication to blood components 
31
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Transfusion Medicine Handbook 3rd Edition

 
3.19  Documentation of transfusion 
31
 
3.20  Local systems and procedures 
32
 
3.21  Reporting of adverse events 
33
4.  BLOOD COMPONENTS 
34
 
4.1  ABO blood groups and antibodies 
34
 
4.2  Avoiding abo incompatible transfusions 
34
 
4.3  RhD antigen 
35
 
4.4  Other blood group systems 
36
 
4.5  Cytomegalovirus (CMV) 
36
  4.6 Irradiation 
36
 
4.7  Blood components available from NZBS 
39
 
4.8  Red blood components 
46
 
4.9  Platelet components 
48
 
4.10  Granulocyte components 
51
 
4.11  Plasma components 
52
 
4.12  Fresh frozen plasma 
53
 
4.13  Cryosupernatant apheresis - high fibrinogen 
55
 
4.14  Cryosupernatant plasma 
56
5.  FRACTIONATED PRODUCTS 
57
 
5.1  Coagulation factors 
58
 
5.1.1 Biostate® (Factor VIII) 
58
 
5.1.2 MonoFIX®-VF (Factor IX) 
60
 
5.1.3 Prothrombinex®-VF (Factors II, IX and X) 
62
 
5.1.4  FEIBA NF® (Factor VIII inhibitor bypassing fraction) 
64
 
5.1.5 RiaSTAP® (Fibrinogen) 
67
 
5.1.6 Fibrogammin® P (Factor XIII) 
68
 
5.2  Natural inhibitors of coagulation 
70
 
5.2.1 Thrombotrol®-VF (Antithrombin III) 
70
 
5.2.2  Ceprotin (Protein C) 
70
 
5.3  Albumin solutions 
71
 
5.3.1 Albumex® 4 (Human albumin 4%) 
71
 
5.3.2 Albumex® 20 (Human albumin 20%) 
73
 
5.4  Immunoglobulin preparations 
76
 
5.4.1  Normal immunoglobulin-VF 
77
 
5.4.2  Hepatitis B immunoglobulin-VF 
80
 
5.4.3  HyperHEP™ S/D 
81
 
5.4.4  Tetanus immunoglobulin-VF 
82
 
5.4.5  Zoster immunoglobulin-VF 
84
 
5.4.6 Berirab® P (Rabies immunoglobulin) 
86
 
5.4.7  Rh(D) immunoglobulin-VF (Anti-D immunoglobulin) 
86
 
5.4.8 Rhophylac® (Anti-D immunoglobulin) 
89
 
5.4.9 Intragam® P (Normal immunoglobulin, intravenous, IVIg) 
90
 
5.4.10 Privigen® (Normal immunoglobulin, intravenous, IVIg)  
93
Transfusion Medicine Handbook 3rd Edition 
Page 3

 
5.4.11 Evogam® (Normal immunoglobulin, subcutaneous, SCIg)  
98
 
5.5  Other products 
100
 
5.5.1 Berinert® P (C1-esterase inhibitor) 
100
 
5.5.2  Products from Australian Red Cross Blood Service (ARCBS)  100
6.  SPECIAL CIRCUMSTANCES 
101
 
6.1  Management of acute blood loss 
101
 
6.2  Massive transfusion protocol (MTP) 
106
 
6.3   Complications of acute blood loss associated with large volume 
transfusions 108
 
6.4  Avoidable haemostatic problems in elective surgery 
109
 
6.4.1 Warfarin 
109
 
6.4.2  Non-vitamin K-dependent oral anticoagulants (NOAC) 
110
 
6.4.3 Aspirin 
111
 
6.4.4  Non-steroidal anti-inflammatory drugs (NSAID) 
111
 
6.4.5 P2Y  adenosine diphosphate (ADP) receptor inhibitors 
111
12
 
6.4.6  Platelet glycoprotein IIb (GPIIb) and IIIa (GPIIIa) inhibitors 
112
 
6.5  Oral anticoagulant induced bleeding or overdose 
113
 
6.5.1 Warfarin 
113
 
6.5.2  Non-vitamin K-dependent oral anticoagulants (NOAC) 
115
 
6.6  Thrombolytic therapy 
117
 
6.7  Disseminated intravascular coagulation (DIC) 
117 
 
6.8  Cardiopulmonary bypass 
117 
 
6.9  Haemolytic disease of the fetus and newborn (HDFN) 
118 
 
6.10  Intrauterine transfusion (IUT) 
123 
 
6.11  Transfusion of the newborn 
124
 
6.12  Neonatal autoimmune thrombocytopenia 
126
 
6.13  Fetal and neonatal alloimmune thrombocytopenia (FNAIT) 
127
 
6.14  Individuals refusing blood transfusion 
128
7.  ADVERSE EFFECTS OF TRANSFUSION 
129
  7.1 Overview 
129
 
7.2  Reporting adverse reactions or events 
129
 
7.3  Guidelines for the management of adverse transfusion reactions 
131
 
7.4  Febrile non-haemolytic transfusion reaction 
144
 
7.5  Allergic & anaphylactic transfusion reaction 
144
 
7.6  Hypotensive transfusion reaction 
145
 
7.7  Acute haemolytic transfusion reaction 
145
 
7.8  Delayed haemolytic transfusion reaction 
146
 
7.9  Bacterial sepsis 
146
 
7.10  Post-transfusion purpura 
147
 
7.11  Transfusion-associated circulatory overload 
147
 
7.12  Transfusion-related acute lung injury 
148
 
7.13  Transfusion-associated dyspnoea 
149
 
7.14  Transfusion-associated graft-versus-host disease 
149
 
7.15  Iron overload / haemosiderosis 
150
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Transfusion Medicine Handbook 3rd Edition

 
7.16  Transfusion-related immunosuppression  
150
 
7.17  Transfusion-transmitted infection 
150
 
7.18  Other infectious agents  
151
 
7.19  Adverse event data 
151
 
7.20  Other complications 
152
8.  CLINICAL ALTERNATIVES AND APPLICATIONS 
153
 
8.1  Autologous blood collection and transfusion 
153
 
8.2  Non-blood plasma volume expanders 
154
 
8.3  Oxygen carrying compounds 
155
 
8.4  Haemopoietic growth factors 
155
 
8.5  Recombinant coagulation factors 
157
 
8.6  Desmopressin acetate (Octostim®, Minirin®) 157
 
8.7  Tranexamic acid (Cyklokapron®) 159
 
8.8  Iron supplementation 
160
9.  OTHER SERVICES PROVIDED BY NZBS 
162
 
9.1  Therapeutic apheresis 
162
 
9.2  Therapeutic venesection 
162
 
9.3  Tissue Bank 
163
 
9.4  Autologous serum eye drops 
163
 
9.5  Reference Laboratory (Immunohaematology) 
164
 
9.6  Tissue Typing Laboratory 
164
10. NZBS SAMPLE REQUIREMENTS 
166
Transfusion Medicine Handbook 3rd Edition 
Page 5

ABBREVIATIONS AND GLOSSARY
ABG 
Arterial blood gas
ACE 
Angiotensin-converting enzyme 
ACS 
Acute coronary syndrome
ACT  
Activated clotting time 
ADAMTS-13 
A disintegrin and metalloproteinase with a thrombospondin 
type 1 motif, member 13
ADP 
Adenosine diphosphate
Adverse event 
Untoward occurrence associated with the collection, testing, 
processing, storage and distribution of blood components 
and fractionated products. Serious adverse events are those 
which may lead to death or to life-threatening, disabling or 
incapacitating conditions for donors/patients, or which result 
in, or prolong, hospitalisation or morbidity.
Adverse reaction 
Untoward response in a donor or patient associated with the 
collection or transfusion of blood components and fractionated 
products. Serious adverse reactions are those which may 
lead to death or to life-threatening, disabling or incapacitating 
conditions or which result in, or prolong, hospitalisation or 
morbidity.
AHF 
Antihemophilic factor 
AHTR 
Acute haemolytic transfusion reaction
AIDS 
Acquired immunodeficiency syndrome
AIHA 
Autoimmune haemolytic anaemia
ALI 
Acute lung injury
Allogeneic blood 
Collected from one individual and intended for use by another 
individual (as in allogeneic blood donation).
ANH 
Acute normovolaemic haemodilution
Anti-HBs 
Antibody to hepatitis B surface antigen (HBsAg). The presence 
of anti-HBs is generally interpreted as indicating recovery and 
immunity from hepatitis B virus (HBV) infection. Anti-HBs also 
develops in a person who has been successfully vaccinated 
against hepatitis B.
ANZSBT 
Australian and New Zealand Society of Blood Transfusion
APTT 
Activated partial thromboplastin time
ARCBS 
Australian Red Cross Blood Service
ARDS 
Adult respiratory distress syndrome
ASH 
American Society of Hematology
ASTH 
Australasian Society of Thrombosis and Haemostasis
ATG 
Anti-thymocyte globulin
Autologous blood  Collected from an individual and intended for their own use (as 
in autologous blood donation).
Page 6 
Transfusion Medicine Handbook 3rd Edition

ATIII 
Antithrombin III
BCSH 
The British Committee for Standards in Haematology
Blood component  A therapeutic constituent separated from human blood (red 
cells, platelets, fresh frozen plasma, cryoprecipitate and white 
cells).
Blood (fractionated) A therapeutic protein fraction prepared from large pools 
product  
of human plasma under pharmaceutical conditions, e.g., 
coagulation factors, albumin, immunoglobulins.
BMI 
Body mass index
BMS  
Blood management system
BNP  
B-type natriuretic peptide 
BU 
Bethesda unit
CHAD  
Cold haemagglutinin disease
CMO 
Chief Medical Officer 
CMV 
Cytomegalovirus is a member of the herpesvirus family, 
transmissible by transfusion, and which may cause disease in 
immunosuppressed patients.
CNS 
Central nervous system
CoE 
Council of Europe
CPAP 
Continuous positive airways pressure
CPD / CPDA 
Citrate phosphate dextrose and citrate phosphate dextrose 
adenine anticoagulant solutions used when collecting blood 
donations.
CSL 
Compound sodium lactate
CSL Behring 
A manufacturer of plasma therapies whose name derives 
from the merger of several parent companies  including CSL 
(Commonwealth Serum Laboratories)  Limited and ZLB 
Behring.
CVP 
Central venous pressure
DAT 
Direct antigobulin (Coombs) test
DDAVP 
1-desamino-8-d-arginine vasopressin (Desmopressin)
DHB 
District Health Board
DHTR 
Delayed haemolytic transfusion reaction
DIC 
Disseminated intravascular coagulation
DNA  
Deoxyribonucleic acid
DSTR 
Delayed serologic transfusion reaction
ECG Electrocardiogram
ECMO  
Extracorporeal membrane oxygenation
EDTA 
Ethylenediaminetetraacetic acid
eGFR 
Estimated glomerular filtration rate
EPO Erythropoietin
Transfusion Medicine Handbook 3rd Edition 
Page 7

FBC 
Full blood count
FEIBA 
Factor VIII inhibitor bypassing activity
FFP 
Fresh frozen plasma
FIX 
Factor IX
FMH 
Fetomaternal haemorrhage
FNAIT 
Fetal and neonatal alloimmune thrombocytopenia
FNHTR 
Febrile non-haemolytic transfusion reaction
Fractionated 
A therapeutic protein fraction prepared from large pools 
product  
of human plasma under pharmaceutical conditions, e.g., 
coagulation factors, albumin, immunoglobulins.
FVIII 
Factor VIII
FXIII 
Factor XIII
G-CSF 
Granulocyte-colony stimulating factor
GP Glycoprotein 
GVHD 
Graft-versus-host disease
HAE  
Hereditary angioedema
HBsAg 
Hepatitis B surface antigen; a serologic marker on the surface 
of hepatitis B virus (HBV). It can be detected in high levels 
in serum during acute or chronic hepatitis. The presence of 
HBsAg indicates that a person is infectious. 
HBV 
Hepatitis B virus
HCV 
Hepatitis C virus
HDFN 
Haemolytic disease of the fetus and newborn
HES  
Hydroxyethyl starch
HFE 
High Iron Fe gene; mutations of HFE are responsible for 
genetic haemachromatosis.
HLA  
Human leucocyte antigen
HPA 
Human platelet antigen
HPC 
Haematopoietic progenitor cell
HIT 
Heparin-induced thrombocytopenia
HIV 
Human immunodeficiency virus
HSCT 
Haematopoietic stem cell transplant
HTC 
Hospital transfusion committee
HTLV 
Human T-cell lymphotrophic virus
HUS 
Haemolytic uraemic syndrome
ICH 
Intracranial haemorrhage
IgA 
Immunoglobulin A
IgG 
Immunoglobulin G
IgM 
Immunoglobulin M
INR 
International normalised ratio
Page 8 
Transfusion Medicine Handbook 3rd Edition

ITP 
Immune thrombocytopenic purpura
IVIg 
Intravenous immunoglobulin
IU 
International units
IUT 
Intrauterine transfusion
JVP 
Jugular venous pressure
LDH 
Lactate dehydrogenase
MBOS 
Maximum blood order schedule
MTP 
Massive transfusion protocol
MO 
Medical Officer
NBA 
Australian National Blood Authority
NHI 
National Health Index
NHMRC 
National Health and Medical Research Council of Australia
NOAC 
Non-vitamin K-dependent oral anticoagulant
NSAID 
Non-steroidal anti-inflammatory drug
NZBS 
New Zealand Blood Service
NZRC 
New Zealand Resuscitation Council
PAS 
Platelet additive solution; nutrient media used in place of 
plasma for platelet storage.
PBSC 
Peripheral blood stem cell
PCC 
Prothrombin complex concentrate 
PCI  
Percutaneous coronary intervention
PHARMAC  
Pharmaceutical Management Agency of the New Zealand 
Government
PID 
Primary immunodeficiency diseases
PLT 
Single therapeutic dose of platelets
PT 
 Prothrombin  time
PTP 
Post-transfusion purpura
RAADP 
Routine antenatal anti-D prophylaxis
RANZCOG  
Royal Australian and New Zealand College of Obstetricians 
and Gynaecologists
RCNA  
Royal College of Nursing of Australia
RCo 
Ristocetin cofactor
Resuspended 
Red cells from which the majority of plasma has been removed 
red cells  
and replaced with a nutrient or preservative solution, e.g., 
saline, adenine, glucose, mannitol (SAG-M)
RhD 
RhD red cell antigen
RNA 
Ribonucleic acid
SCIg 
Subcutaneous immunoglobulin
SED  
Serum eye drops
Transfusion Medicine Handbook 3rd Edition 
Page 9

SHOT 
Serious Hazards of Transfusion; UK haemovigilance 
programme.
TACO 
Transfusion-associated circulatory overload
TAD 
Transfusion-associated dyspnoea
TA-GVHD 
Transfusion-associated graft-versus-host disease
TMS 
Transfusion Medicine Specialist
TNS 
Transfusion Nurse Specialist
TPE 
Therapeutic plasma exchange
TPO Thrombopoietin
TPR 
Temperature/Pulse/Respiratory rate
TRAE  
Transfusion-related adverse event
TRALI 
Transfusion-related acute lung injury
TRIM  
Transfusion-related immunomodulation
TTI 
Transfusion-transmitted infection
TTP 
Thrombotic thrombocytopenic purpura
vCJD 
Variant Creutzfeldt-Jakob disease
vWF 
von Willebrand factor
vWD 
von Willebrand disease
VZV 
Varicella zoster virus
Whole blood 
Blood collected from a donor prior to separation into 
constituent red cells, platelets and plasma. 
WBCT  
Whole blood clotting time 
WBIT  
Wrong blood in tube
WHO 
World Health Organisation 
Page 10 
Transfusion Medicine Handbook 3rd Edition

FOREWORD
This handbook is designed to assist hospital staff and other health professionals in 
modern transfusion medicine practice, particularly those who are prescribing and 
administering blood products. In addition to information about the blood products 
and services offered by the NZBS, it provides a framework for the clinical indications 
for their use, the procedures for administration, and the management of adverse 
reactions in patients.
The NZBS Clinical Compendium, NZBS Manufacturing Standards, hospital clinical 
policies and other departmental manuals cover aspects of these guidelines in more 
detail. The contents of the NZBS Clinical Compendium are also available on the 
NZBS website (www.nzblood.co.nz). If information in these should not accord with 
the principles outlined in this document, the differences should be referred in writing 
to the New Zealand Blood Service, attention National Medical Director:
The National Medical Director 
 
New Zealand Blood Service 
 
Private Bag 92071 
 
Auckland 1142
Telephone  (09) 523 5733 
 
Facsimile   (09) 523 5754
The assistance of Transfusion Medicine Specialists and Transfusion Nurse Specialists in 
the review of these guidelines is gratefully acknowledged. Comments and suggestions 
for improvements in future editions are invited and should be addressed to the National 
Medical Director. 
If assistance is required for the management of transfusion support for patients in 
particular clinical circumstances further information and advice can always be obtained 
from NZBS Transfusion Medicine Specialists.
Transfusion Medicine Handbook 3rd Edition 
Page 11

1
INTRODUCTION
1.1  
Audience
Many people play an essential part in ensuring that the right blood components and 
products are given to the right patient at the right time. This handbook is therefore intended 
for all staff responsible for prescribing, supplying and administering blood components 
and fractionated products. They include:■  
■  
Registered medical practitioners, nurses and midwives who assess patients 
and who prescribe and order blood components and fractionated products to 
be transfused.
■  
Phlebotomists and others who collect and send pretransfusion samples. 
■  
Laboratory staff who ensure that blood components are compatible for 
transfusion. 
■  
Orderlies and other personnel who deliver blood components and fractionated 
products to hospital wards and clinics where patients are transfused. 
■  
Nurses and other clinical staff who check that, before being administered, the 
supplied blood components and fractionated products are intended for the 
identified patient, and who then observe the patient during and after the transfusion.
■  
Medical and nursing students involved in any of the above activities.
■  
Telephone operators who may have to make vital contacts in an emergency.
1.2  
Evidence
Correctly used, transfusion can save lives and provide numerous clinical benefits. 
However, the effectiveness of many current transfusion practices has not been 
rigorously proven by clinical trials. It is not possible to offer complete evidence-based 
guidelines for practice. Where good evidence is not available, the contents of this 
handbook reflect best efforts to give a balanced view of current opinion about the 
clinical practice of transfusion for patients in New Zealand.
1.3  
Clinical Practice Guidelines
Australasian guidelines are available for the administration and appropriate use of blood 
components and fractionated products. These have been developed by the Australian 
& New Zealand Society of Blood Transfusion (ANZSBT) and the Australian National 
Blood Authority (NBA) and supported by specialist colleges and medical specialists 
of both Australia and New Zealand. 
The NBA Patient Blood Management Guidelines, approved by the Australian National 
Health and Medical Research Council (NHMRC), cover the use of blood components 
(red blood cells, platelets, fresh frozen plasma, cryoprecipitate) and are available from 
the NBA website at www.blood.gov.au/pbm-guidelines. 
A summary of transfusion guidelines can be found on the reverse of the NZBS 
Request for Blood Components or Products form and are presented in more detail in 
Chapter 4: Blood Components. Other sources of information that may prove useful 
are listed in Table 1.1.
Page 12 
Transfusion Medicine Handbook 3rd Edition

However, the most important factors driving the success of moves toward improved 
clinical quality reside within New Zealand hospitals (both DHB and private). Evidence 
from the New Zealand National Haemovigilance Programme and similar programmes 
overseas, such as the UK’s Serious Hazards of Transfusion scheme (SHOT), shows 
that most serious errors relating to transfusion practice arise from administrative and 
clerical errors, most of which are avoidable. 
Table 1.1  Sources of Information
Organisation
Website
New Zealand Blood Service
www.nzblood.co.nz
NZBS Blood Resource
www.clinicaldata.nzblood.co.nz/
resourcefolder
Australian Red Cross Blood Service
www.transfusion.com.au
Australian National Blood Authority
www.blood.gov.au
Australian and New Zealand Society of 
www.anzsbt.org.au
Blood Transfusion (ANZSBT)
Joint UK Blood Transfusion and Tissue 
www.transfusionguidelines.org.uk
Services Professional Advisory Committee
British Committee for Standards in 
www.bcshguidelines.com
Haematology (BCSH)
UK Serious Hazards of Transfusion scheme 
www.shotuk.org
(SHOT)
NZ Ministry of Health
www.moh.govt.nz
New Zealand legislation
www.legislation.govt.nz
1.4 Haemovigilance 
Blood components and fractionated products are biological in nature and carry 
inherent risks in respect of infection or reactions in the recipient. Common and, for 
the most part, minor reactions include febrile non-haemolytic and allergic transfusion 
reactions. A small number of problems account for the majority of difficulties and 
dangers associated with transfusion, for example delay in obtaining blood components 
needed urgently, transfusing blood components and fractionated products intended 
for another patient, over-transfusion leading to circulatory overload and pulmonary 
oedema, and transfusion-transmitted bacterial infections. Fortunately, the risk of 
transfusion-transmitted viral infections such as HIV, hepatitis B and hepatitis C is 
relatively low when compared with other risks.
Clinical staff have the responsibility for recognising and reporting transfusion-related 
complications to the blood bank, NZBS Transfusion Medicine Specialist/Medical Officer 
or a Transfusion Nurse Specialist. 
It is the task of NZBS and manufacturers of fractionated products to ensure that blood 
supply and transfusion practice is as safe as possible. Similarly, local hospital blood 
bank staff and the hospital transfusion committee should ensure that adverse events 
are effectively investigated and reported.
Transfusion Medicine Handbook 3rd Edition 
Page 13

Some Common Causes of Problems
Most of the problems associated with transfusion that cause delays and may put 
the patient at risk are caused by poor communication, failure to follow documented 
procedures and inadequately trained staff. The most frequently occurring problems are:
■  
Prescribing blood components and fractionated products that are not required by 
the patient or are not the most suitable treatment for the patient’s clinical condition.
■  
Incomplete or inaccurate completion of request forms or sample tube labels.
■  
Improper collection of samples possibly leading to ‘wrong blood in tube’ (WBIT) 
incidents.
■  
Delays caused by a failure to communicate accurately when and where blood 
components and fractionated products are needed.
■  
Transfusion of blood components and fractionated products that are intended 
for another patient.
■  
Failure to recognise and appropriately manage an adverse reaction occurring 
during transfusion.
Notification and Investigation of an Adverse Transfusion Reaction
NZBS has produced a form for notifying the blood bank of the occurrence of a 
transfusion reaction. Copies of the Notification and Investigation of Adverse Transfusion 
Reaction form are normally available in each ward or from the blood bank. 
On the reverse side of this form are guidelines for the management of adverse 
transfusion reactions to assist clinical staff in the immediate care of the patient.
Haemovigilance Activities
NZBS is obliged to monitor the occurrence of adverse events during the transfusion 
process from vein-to-vein (i.e., from donation collection through to transfusion), in line 
with principles contained in the Council of Europe Guide to the Preparation, Use and 
Quality Assurance of Blood Components. Donor incidents, specimen labelling errors, 
blood bank errors, bedside checking errors and transfusion reactions are all examples 
of activities which fall under the umbrella of ‘haemovigilance’ and for which NZBS has 
systems in place to capture information. 
In turn, the National Haemovigilance Programme specifically receives notification 
of adverse events that occur during, or as a result of, transfusion. All New Zealand 
hospitals and blood banks participate in the programme, reporting any transfusion-
related adverse events experienced by patients in the hospitals they serve. NZBS also 
works with hospitals to ensure that adverse events are appropriately managed and 
reported in a timely manner. 
Transfusion is a complex process involving many different staff groups in the hospital. 
Any failure in the transfusion chain has the potential to cause significant harm to, or even 
death of, patients. Therefore all personnel involved in the transfusion process should 
be encouraged to be vigilant and report any untoward events that they may observe. 
Further information about the nature of adverse effects of transfusion and how they 
should be reported to NZBS can be found in Chapter 7: Adverse Events of Transfusion.
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2
COLLECTION, TESTING AND PROCESSING OF BLOOD 
DONATIONS

2.1 
Blood Donors  
Blood donors are essential to NZBS and the national blood supply. Up to 800 donors 
are needed each working day to meet the country’s transfusion needs and the supply 
of plasma for the manufacture of fractionated products. A great debt is therefore owed 
to the many volunteer donors who so willingly help in this way. 
There are five categories of blood donation:
■  
Whole blood donation where a single unit of blood is collected. Whole blood 
donors usually give about 470 mL of blood (with an additional 30 mL taken for 
routine testing) and can donate up to four times per year.
■  
Apheresis donation where plasma, platelets or white cells are specifically 
collected from the donor’s whole blood using a machine known as a cell-
separator. Once these components are harvested, the donor’s red cells are 
usually returned to them. Apheresis donors can donate more frequently than 
whole blood donors and as often as every two weeks.
■  
Pre-operative autologous donation where blood components are collected 
from patients for transfusion to themselves during elective surgery. Refer to 
Section 8.1: Autologous Blood Col ection and Transfusion for further information.
■  
Directed donation where one individual seeks to identify another individual 
who will donate to provide blood components for either themselves or a close 
family relative.
■  
Selected donation where NZBS identifies donors to provide blood components 
for recipients with rare blood types, or with red cell or platelet antibodies.
2.2 
Donor Selection Criteria
The donor selection process contributes significantly to the safety of the donor pool 
and the blood supply:
■  
Whole blood donors are accepted from their 16th birthday up to their 66th 
birthday. Established donors (those who have donated in the previous two years) 
can donate up to their 71st birthday and thereafter up to their 76th birthday, 
subject to annual medical review by an NZBS Medical Officer. 
■  
Donors must be in good health and weigh more than 50 kg. This ensures that the 
process of donation is not detrimental to the donor’s health as well as protecting 
the recipient from blood-borne infectious disease (such as bacterial sepsis, HIV, 
hepatitis B and hepatitis C, malaria and variant Creutzfeldt-Jakob disease), donor 
medications or other contaminants that could be harmful to them. 
■  
At each donation the donor completes a detailed health questionnaire and signs 
a declaration that the health information provided is correct. 
■  
The donor’s haemoglobin level is checked each time they donate. 
Transfusion Medicine Handbook 3rd Edition 
Page 15

■  
The donor’s completed medical history is evaluated by a suitably qualified health 
professional and the donor accepted or deferred accordingly.
The NZBS website (www.nzblood.co.nz) provides detailed information on the current 
donor eligibility and deferral criteria.
2.3 
Self-Sufficiency and the Volunteer Status of Donors
New Zealand has adopted recommendations of the World Health Organisation (WHO) 
in achieving self-sufficiency in safe blood supply, based on voluntary non-remunerated 
blood donation (VNRBD). 
Defined by the WHO, self-sufficiency means that the national needs of patients are met 
in a timely manner, that patients have equitable access to transfusion services, blood 
components and fractionated products, and that these are obtained from VNRBD of 
national, and where needed, of regional origin, such as from neighbouring countries.
Donation is considered voluntary and non-remunerated if the person gives blood, 
plasma or cellular components of his/her own free will and receives no payment for 
it, either in the form of cash, or in kind which could be considered a substitute for 
money. This would include time off work other than that reasonably needed for the 
donation and travel. Small tokens, refreshments and reimbursements of direct travel 
costs are compatible with voluntary, non-remunerated donation.
2.4 
Informed Consent for Donation
Informed consent is a requirement of the Code of Health and Disability Services 
Consumer’s Rights (1996)
. Donors are required to be fully informed about the donation 
process, the risks involved and their obligations as donors. The donor’s consent is 
obtained when they complete the health questionnaire.
In consenting to donate, donors agree to the testing of their blood for blood group 
and evidence of infectious diseases, as well as the use of their blood for transfusion, 
teaching, diagnostic purposes or quality testing. 
Information leaflets about the blood donation process and blood safety along with 
a copy of the health questionnaire are available from NZBS blood centres and also 
from the NZBS website.
2.5 
 Apheresis  Donation
Apheresis is a procedure used to collect:
■  
Plasma (plasmapheresis)
■  
Cellular components (cytapheresis) including:
 

Platelets (plateletpheresis)
 

Granulocytes (granulocytapheresis)
 

Haematopoietic progenitor cells (HPCs) derived from peripheral blood
Red cells can also be collected by erythrocytapheresis (although NZBS does not 
offer this service). 
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Transfusion Medicine Handbook 3rd Edition

2.6 
Directed and Selected Donation 
When a person seeks to identify another individual who will donate blood to provide 
blood components for either themselves or a close family relative, the practice is 
termed a directed donation. The request usually occurs within family relationships, in 
particular parents of children, where there may be significant emotional anxiety reflecting 
a concern regarding the perceived safety of a transfusion. There is no evidence that 
directed donations either lead to improved patient care or reduce the risk of acquiring 
transfusion-transmitted infections. As a result, NZBS does not support the practice of 
directed donations and will discourage such requests. However, if a directed donation 
is collected, the procedures for collecting, testing, storing, handling and transfusing 
the unit must follow the procedures recommended for non-directed allogeneic blood 
donations. For the purposes of directed blood donations only, the meaning of the 
terms donor and donation refer to a volunteer who provides blood that is to be used 
for a purpose specified by the person providing the blood, or to the derived blood 
components, respectively. If a directed donation is not used for the purpose specified, 
i.e., transfusion to the intended recipient, the donation and associated components 
will be discarded and not made available for other recipients.
In some circumstances it may be necessary for NZBS to seek a compatible donor 
from relatives. This practice is at the discretion of a Transfusion Medicine Specialist 
and involves a selected donation, not a directed donation. Donors are selected for 
matched platelets, peripheral blood stem cells and rare blood groups.
Apheresis donors should normally meet the requirements for whole blood donation. 
Exceptions to this must be authorised by a NZBS Transfusion Medicine Specialist/
Medical Officer. Such exceptions will normally only be made when the plasma or 
platelets are of unusual therapeutic value and only when the NZBS Transfusion 
Medicine Specialist/Medical Officer, who is aware of the health status of the donor, 
has documented that the donor’s health permits apheresis donation.
2.7 Haemochromatosis
Genetic or hereditary haemochromatosis is mainly associated with a defect in the 
HFE (High Iron Fe) gene. HFE helps regulate the amount of iron absorbed from food. 
There are two important mutations in HFE, namely C282Y and H63D, of which C282Y is 
the most important. When inherited from both parents, C282Y causes a variable increase 
in iron absorption which, if untreated, may lead to iron overload and organ dysfunction. 
Management consists of lifelong monitoring, avoidance of an iron-rich diet and, 
depending on clinical phenotype, therapeutic venesection to deplete iron stores 
followed by maintenance venesection to prevent recurrence of iron overload. 
Patients who are clinically well and meet all blood donor acceptance criteria may be 
enrolled as normal blood donors. NZBS checks the ferritin level periodically while iron 
depletion is in progress. Once stable iron-deplete levels are achieved, annual monitoring 
by the patient’s general practitioner is recommended. 
2.8 
Cord Blood Donation
NZBS currently does not routinely provide this service and all requests for the 
col ection of directed cord stem cel s should be referred to a NZBS Transfusion 
Medicine Specialist.
Transfusion Medicine Handbook 3rd Edition 
Page 17

2.9 
Testing of Donor Blood 
Every unit of blood collected is tested for the following:
■  
ABO and RhD blood groups
■  
Red cell antibodies
■  
Infectious diseases:
 

HIV (HIV Ag/Ab and HIV RNA)
 

Hepatitis B (HBsAg and HBV DNA)
 

Hepatitis C (anti-HCV and HCV RNA)
 

Syphilis (Treponema pallidum antibodies)
Other testing restricted to specific donor groups and, where indicated, individual 
donors or donations:
■  
HTLV-I /II antibody on all new donors
■  
CMV antibody on donations to be used as components for patients at high risk 
from CMV infection 
■  
Plasmodium antibody on donations from malaria-risk donors
■  
Trypanosoma cruzi antibody on donations from Chagas-risk donors
■  
Ferritin on donors failing the haemoglobin screening test
■  
Direct antiglobulin test (DAT) 
■  
Extended red cell antigen typing
■  
HLA antibody on previously pregnant (> 20 weeks gestation) female plateletpheresis 
donors
■  
HLA (human leucocyte antigen) or HPA (human platelet antigen) genotyping 
2.10 Leucodepletion
All blood components for direct clinical transfusion are leucodepleted. Leucodepletion 
is a process for removing white cells (leucocytes) from blood components. This is 
achieved by means of a special filter or by differential centrifugation. Leucodepleted 
blood components should contain < 5 x 106 white cells per unit.
NZBS introduced universal prestorage leucodepletion in July 2001, initially as one of 
a series of precautionary measures against the potential risk of transmission of variant 
Creutzfeldt-Jakob disease (vCJD) by blood transfusion. 
There is good evidence to support the value of leucodepletion in preventing transfusion-
associated transmission of some infectious agents and in reducing some of the adverse 
immunomodulatory effects of allogeneic transfusion:
■  
Reduction in frequency of febrile non-haemolytic transfusion reactions.
■  
Prevention or delay of alloimmunisation to human leucocyte antigens.
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Transfusion Medicine Handbook 3rd Edition

■  
Prevention or delay of platelet refractoriness due to alloimmunisation.
■  
Reduction in the risk of CMV transmission.
Leucodepletion also has other theoretical advantages:
■  
Reducing the risk of other leucocyte-associated blood borne infections, such 
as transmission of HTLV-I/II, and inadvertent bacterial contamination of blood 
components.
■  
May reduce the risk of perioperative infection or cancer recurrence by reducing 
the immunomodulatory effects of blood transfusion.
■  
May prevent some cases of transfusion related acute lung injury (TRALI).
2.11  Processing of Collected Blood to Components
Blood donations are processed into various components including red cells, platelet 
concentrates, fresh frozen plasma and cryoprecipitate. Blood components are prepared 
at NZBS processing centres under strictly controlled manufacturing conditions.
Blood Component Labelling   
Blood components supplied for transfusion have a blood component label applied by 
the manufacturer specific to each individual component type. These labels provide 
important information for those who administer blood components and also allow the 
origins of the component to be traced.
Labels should state the details of the component and its composition, the conditions 
under which it can safely be stored and the date and time of expiry. Components from 
single donors must carry the unique donation number that identifies the donation. 
Compatibility Labels 
 
A ‘compatibility label’ will be applied by the blood bank issuing the component to the 
patient. This label uniquely identifies the patient for whom the component has been 
selected. An essential bedside check before transfusing any blood component is to 
make sure that the details on the compatibility label match exactly those of the patient.
2.12  Processing of Collected Blood to Fractionated Products
Fractionated products, also known as plasma derivatives, are partial y purified 
therapeutic preparations of plasma proteins. They are manufactured in large-scale 
pharmaceutical processes from large volumes of source plasma. For example, each 
batch of Intragam®P typically uses 7.5 - 10 tonnes of plasma (from approximately 
25,000 - 30,000 individual whole blood donations).
The plasma is processed by a variety of techniques classically involving Cohn 
fractionation but more recently chromatographic techniques such as gel filtration, ion 
exchange and affinity chromatography have been used. 
Finally, the purified plasma undergoes specific virus removal or inactivation steps, for 
example heat-treatment, solvent/detergent treatment, incubation at low pH or filtration. 
The final products are supplied as freeze-dried powders or solutions.
All of the plasma obtained by NZBS through the collection of whole blood, together 
with approximately 80% of the apheresis plasma, is forwarded to CSL Behring in 
Melbourne for the manufacture of fractionated products. 
Transfusion Medicine Handbook 3rd Edition 
Page 19

Product labelling 
 
Fractionated products are identified by both the carton packaging and labels of the 
product container. Included with every product is an insert provided by the manufacturer 
with detailed information concerning the product relating to its composition, indication 
for use and administration.
Blood bank labelling 
 
All fractionated products issued to a patient have a computer-generated label attached 
that provides details of the patient and product batch number. This label is used at 
the bedside check of the patient’s identity and then placed in the clinical notes as a 
record of transfusion.
2.13  Blood Components and Fractionated Products as Medicines
Blood components and fractionated products are classified as prescription medicines 
under New Zealand legislation. The Medicines Act 1981, Medicines Regulations 1984, 
Medicines Amendment Regulations 2011 
and Medicines Amendment Act 2013 provide 
the legal framework under which blood components and fractionated products may 
be manufactured and supplied as well as stipulating who may prescribe them. Under 
the regulations, medical practitioners, registered midwives and nurse practitioners all 
have prescribing rights for blood components and fractionated products in accordance 
with their regulated scopes of practice.
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3
GUIDE TO GOOD TRANSFUSION PRACTICE
Both blood components and fractionated products are biologic material and, in 
the case of components containing blood cells, are living human tissues. They are 
prescription medicines intended for use by medical practitioners and midwives in the 
treatment of patients. 
Blood transfusion therapy has had a central role in the advances and practice of modern 
medicine. As in other areas of clinical medicine, prescribers need to consider both 
the benefits and risks of blood transfusion. Professional judgement based on clinical 
evaluation determines selection of blood components and fractionated products, 
dosage, rate of administration and sometimes other decisions in situations not covered 
in this general introduction to blood transfusion practice.
The presence of contaminants such as immunogenic cellular and protein elements, 
viable donor cells and infectious agents in blood cannot be totally avoided and indeed 
may cause undesirable side ef ects in some recipients. The information in this handbook 
cannot therefore be considered or interpreted as an expressed or implied warranty 
of the safety or fitness of the described blood components or fractionated products 
when used for their intended purpose.
3.1 
Clinical Governance
A quality management system is needed wherever transfusion therapy is practised. 
In this context ‘quality’ includes adequate documentation of both the transfusion 
process and its outcomes.
All institutions that transfuse blood components and fractionated products should 
develop and maintain local policies and procedures that reflect best national and 
international transfusion practice. Local policies and procedures should include 
guidance on:
■  
Informed consent.
■  
Requesting blood components and fractionated products.
■  
Collection of blood samples for pretransfusion compatibility testing.
■  
Collection of blood components and fractionated products from the hospital 
blood bank or other sites.
■  
Delivery of blood components and fractionated products to where the transfusion 
is to be given.
■  
Administration of blood components and fractionated products.
■  
Care and monitoring of patients receiving a transfusion.
■  
Documentation of transfusion.
■  
Management and reporting of adverse events.
■  
Staff responsibilities and the training required for these procedures.
Transfusion Medicine Handbook 3rd Edition 
Page 21

3.2 
Prescribing Blood Components and Fractionated Products
Prescribing blood components and fractionated products is normally the responsibility 
of a registered medical practitioner. Registered midwives and nurse practitioners 
have limited prescribing rights as defined by the Medicines Regulations 1984 and 
Medicines Amendment Regulations 2011. For example, registered midwives are able 
to prescribe prescription medicines but only in the course of antenatal, intrapartum 
and postnatal care.
Decisions to transfuse should, taking individual patient needs into account, be based 
on international and regional guidelines such as the Australian National Blood Authority 
Patient Blood Management Guidelines.
It is the responsibility of the prescribing practitioner to ensure that transfusion therapy 
is given only when clearly indicated and that the patient is appropriately monitored 
during the transfusion procedure. 
The following questions should be taken into consideration when deciding to transfuse:
■  
What improvement in the patient’s condition am I aiming to achieve?
■  
Can I minimise blood loss to reduce the patient’s need for transfusion?
■  
Are there any other treatments I should give before making the decision to 
transfuse?
■  
What are the specific indications for transfusing this patient?
■  
Do the benefits of transfusion outweigh the risks to this particular patient?
■  
Has the patient been given a clear explanation of the potential risks and benefits 
of blood transfusion therapy in his or her particular case?
Once the decision to transfuse has been made it is also important to consider the following:
■  
Have I recorded my decision to transfuse and the reasons for transfusion on 
the patient’s chart and completed any documentation used in the ordering or 
administration of blood components or fractionated products?
■  
Will a trained person monitor this patient and respond immediately if any acute 
transfusion reactions occur?
■  
Has crossmatching and other relevant testing been carried out?
Prescribing Unapproved Pharmaceuticals
Practitioners should, where possible, prescribe pharmaceuticals that are approved under 
the Medicines Act 1981. If Practitioners are planning on prescribing an unapproved 
pharmaceutical or a pharmaceutical for an indication for which it is not approved, 
Practitioners should: 
a)   be aware of and comply with their obligations under Section 29 of the Medicines 
Act 1981 and otherwise under that Act and the Medicines Regulations 1984;
b)  be aware of and comply with their obligations under the Health and Disability 
Commissioner’s Code of Consumer Rights, including the requirement to obtain 
informed consent from the patient; and
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Transfusion Medicine Handbook 3rd Edition

c)   exercise their own skill, judgement, expertise and discretion, and make their own 
prescribing decisions with respect to the use of an unapproved pharmaceutical 
or a pharmaceutical for an indication for which it is not approved.
Where medicines, supplied under Section 29 of the Medicines Act, are used for 
emergency situations, the required patient details may be retrospectively provided to 
the supplier.
3.3 
Informed Consent to Receive a Blood Transfusion
Informed consent for transfusion is a requirement of the Code of Health and Disability 
Services Consumers’ Rights
 (a regulation under the Health and Disability Commissioner 
Act 1994
). This requires that patients be provided with information and an explanation 
of the purpose for which blood components and fractionated products are being 
prescribed and that they consent to transfusion. 
Patients or their relatives may be worried about the risks of transfusion. Although most 
patients will be prepared to give consent for a transfusion after receiving appropriate 
information, some will seek and require quite detailed reasons for the transfusion, 
information on the risks involved and the alternatives available (such as autologous 
transfusion). 
Some patients may refuse transfusion for personal or religious reasons, for example 
members of the Jehovah’s Witnesses faith. Some of these patients may be prepared 
to accept fractionated products or other alternatives.
The seeking of informed consent, together with the reasons for the transfusion, should 
be recorded in the clinical record of the patient.
NZBS provides a range of leaflets to support the process of gaining informed consent. 
Copies of these should be available at all sites where blood may be transfused and 
can also be obtained from NZBS Transfusion Nurse Specialists or the hospital blood 
bank. This information is also available on the NZBS website (www.nzblood.co.nz). 
3.4 
Requesting Blood Components and Fractionated Products
The NZBS Request for Blood Components and Products form is used in most New 
Zealand hospitals and follows a prescription written in the patient clinical record. Blood 
components and fractionated products are normally obtained from the hospital blood 
bank and local hospital policies will determine which staff can place orders. It should 
be noted that the form used to request blood components and fractionated products 
is not a prescription.
The request form must:
■  
Correctly identify the patient.
■  
Provide details of any previous transfusion or obstetric history.
■  
Indicate the quantity of the blood component or fractionated product required, 
when it is required and where it should be sent to.
Full and accurate completion of the request form is essential for:
■  
Ensuring that the right quantity and type of blood component or fractionated product 
is made available to the right patient, at the right time, and in the right place.
Transfusion Medicine Handbook 3rd Edition 
Page 23

■  
Minimising the risk of patient identification errors. 
■  
Alerting the blood bank to the possibility of antibodies, based on a history of 
previous transfusions or pregnancy, in which case suitably matched blood may 
be required.
Patients who, at the time of admission, cannot be reliably identified must be given 
an identity band with a unique number. This number must be used to identify this 
patient until full and correct details are available and are properly communicated to 
the blood bank.
3.5 
Blood Stock Management: The Maximum Blood Order Schedule
The maximum blood order schedule (MBOS) is one way a blood bank manages blood 
stock. A typical MBOS lists surgical and other interventional procedures along with the 
number of red cell units normally required in preparedness for transfusion in association 
with these procedures. The number of units is determined by analysis of historical 
blood usage figures. Many laboratories formulate a MBOS based on local surgical 
experience, while others adopt a generic schedule. An example of such a schedule 
is available in the 2016 Australian and New Zealand Society of Blood Transfusion 
(ANZSBT) Guidelines for Transfusion, Pre and Postnatal Immunohaematology Testing 
(www.anzsbt.org.au)
.
The goal of the MBOS is to promote efficient use of red cells. It provides guidance to 
(junior) medical staff on the number of units of red cells likely to be required for various 
surgical procedures and is also a valuable guide for the blood bank, particularly those 
which routinely perform serological crossmatching (generally smaller facilities). For 
procedures where red cells are seldom required, the MBOS will simply recommend 
that no units should be crossmatched and a group and screen performed. 
If more red cells are ordered for a patient than required or they are held crossmatched 
unnecessarily, then these units may be unavailable for other patients and there is a 
chance that the red cells will expire before being used. The clinician therefore needs 
to have a valid rationale to order more units than is mandated by the MBOS.
If the patient has a positive antibody screen or special transfusion requirements the 
blood bank may adjust the number of red cells crossmatched (from what is specified 
in the MBOS) to avoid potential problems should transfusion be required.
Together, the MBOS, regular monitoring of crossmatch-to-transfusion (C:T) ratios 
for individual surgical procedures and adoption of a ‘group and screen’ policy are 
all helpful in ensuring maximum use of the available stock of red cell components.
3.6 
Collecting Blood Samples for Pretransfusion Testing
Correct identification of the patient before collecting the pretransfusion sample is vital 
in avoiding ‘wrong blood in tube’ (WBIT) episodes. Only when the patient’s identity 
is positively confirmed can the request form be completed, blood sample taken and 
sample tube labelled. 
Sample collection must be performed in accordance with hospital policy (or the 
laboratory manual) and observe the following principles:
■  
At the time of taking the sample ask the patient (if conscious or rational) to state 
their given name(s), family name and date of birth.
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Transfusion Medicine Handbook 3rd Edition

■  
Check this information against the patient’s identification bracelet and details 
on the request form to make sure that the details are identical.
■  
Collect the blood sample into the correct sample tube.
■  
Hand label the sample* with the following information:
 

Patient’s family name
 

Patient’s given name(s)
 

Patient’s NHI number
 

Patient’s date of birth
 

Signature or initials of the collector
 

Date and time sample collected
* Please note: The information on the request form will be checked against that on the sample tube 
and both must be identical. NZBS Blood Bank does not accept pretransfusion samples labelled 
with pre-printed labels.

■  
Sample tubes must be hand labelled in the presence of the patient, at the time 
the blood is collected, by the person who obtained the sample:
 

Sample labelling must never be delegated to a third party.
 

 Sample tubes must not be prelabelled before the sample is obtained 
because of the risk of bleeding the patient’s blood into the wrong tubes.
 

 Sample tubes must never be labelled away from the patient’s presence 
because of the risk of labelling the sample tube and/or request form with 
another patient’s details. 
■  
In the case of an unconscious (or irrational) patient, alternative identification 
procedures may be necessary, for example verification by the next of kin, as 
well as checking the identification wristband.
■  
The sample acceptance criteria used by NZBS are based on ANZSBT Guidelines 
for Transfusion, Pre and Postnatal Immunohaematology Testing
. Blood Bank staff 
are not authorised to accept samples which do not meet labelling requirements. 
Where necessary these will be rejected and new samples requested. Where a 
dispute arises in relation to a sample, the final decision on suitability for testing 
will lie with an NZBS Transfusion Medicine Specialist/Medical Officer. 
3.7 
Pretransfusion Testing
Using the pretransfusion blood sample taken from the patient, the blood bank will 
perform a ‘group and screen’ (sometimes also referred to as ‘group and hold’, 
‘group and save’ or ‘type and screen’). A ‘group and screen’ consists of the following 
procedures: 
■  
ABO and RhD group. 
■  
Antibody screen.
■  
Checking for previous or duplicate records for the patient and, when these are 
available, comparing current results with historical findings.
Transfusion Medicine Handbook 3rd Edition 
Page 25

If red cells are subsequently required the blood bank will select appropriate donor 
units and perform a final compatibility check. 
Various approaches exist for compatibility testing. This may involve either a serological 
crossmatch of the patient’s plasma versus donor red cells or, in some hospitals, an 
electronic crossmatch, where the blood bank computer performs the last compatibility 
check. Once pretransfusion testing is completed blood can be issued to the ward 
or operating theatre.
3.8 
Patients with a Positive Antibody Screen
If the patient is found to have a clinically significant red cell antibody during antibody 
screening, blood that does not have the corresponding antigen will be needed for 
transfusion. The relevant antigen-negative donor blood is selected and crossmatched 
against the patient’s plasma. This can be a time-consuming process but is necessary 
if the patient is to receive compatible blood.
If there is insufficient time for full identification of the antibody or to obtain antigen-
negative units, transfusion of (potentially) incompatible blood may be recommended. 
In these circumstances a NZBS Transfusion Medicine Specialist/Medical Officer will 
contact the clinical staff to discuss the comparative risks of delaying transfusion versus 
transfusing potentially incompatible blood.
3.9 
Sample Validity (‘72-Hour Rule’)
The sample validity period, during which time a pretransfusion sample may be held 
and used to provide crossmatched blood, depends on the patient’s transfusion or 
obstetric history. 
Red cell antibodies can rapidly appear in response to stimulation by transfused red 
cells or as a result of pregnancy. Consequently, if in the three months preceding 
collection of the pretransfusion sample the patient has been transfused with red cells 
(or platelets), is currently pregnant (or has been), the sample will have a validity of 72 
hours. This is known as the ‘72-hour rule’. 
Longer expiry times are applied if the patient is known not to have a history of 
transfusion or pregnancy. 
Table 3.1:  Sample Validity Criteria
Patient History
Sample Expiry
Patient transfused or pregnant in previous 3 months (or 
72 hours
history not known) or has history of clinically significant red cell 
antibodies
Patient neither transfused nor pregnant in last 3 months and no 
7 days
history of clinically significant red cell antibodies
Preadmission sample and patient neither transfused nor 
21 days
pregnant in last 3 months and no history of clinically significant 
red cell antibodies
For preadmission samples, the requirement for 21-day expiry must be clearly noted 
on the request form along with the proposed date of surgery or procedure. Details of 
Page 26 
Transfusion Medicine Handbook 3rd Edition

whether or not the patient has a transfusion and/or obstetric history must also be given. 
Failure to provide this information will result in the sample being given a 72-hour expiry.
Once a transfusion episode has commenced the pretransfusion sample, and any 
associated results, will cease to be valid either at the original expiry of the sample, or 
72 hours from when transfusion of the first unit commenced, whichever eventuates first. 
If further transfusions are necessary a new sample will be required. Each new sample 
will have an expiry of 72 hours until a gap of three months between transfusions (or 
since pregnancy) has occurred.
Extensions to sample expiry times may be possible at the discretion of a NZBS 
Transfusion Medicine Specialist/Medical Officer. If you have any queries regarding 
sample validity contact the local blood bank for advice.
3.10  Provision of Red Cells in an Emergency
The nature and availability of red cells in an emergency situation depends on the 
urgency with which blood is required and the extent of pretransfusion testing that can 
be completed within the appropriate response time.
Table 3.2:  Availability of Red Cell Units
Tests Completed
Units Selected
Availability
None
Emergency O RhD negative blood 
Immediate 
(uncrossmatched)
Limited testing  
ABO/RhD group specific blood 
15 minutes 
(ABO/RhD type only) 
(uncrossmatched)
All testing  
ABO/RhD group specific and 
45 minutes1 
(Full ‘Group and Screen’) 
compatible blood
1Assuming a negative antibody screen.
If red cells are required immediately and before pretransfusion testing can be 
completed, the use of emergency group O RhD negative units should be considered. 
As stocks of group O RhD negative red cells are limited, a timely switch to red cells of 
the patient’s group is recommended. It should be noted that whilst emergency red cells 
are group O RhD negative, complete serological compatibility cannot be guaranteed 
as the patient may have a red cell antibody. 
Where time allows a confirmed ABO/RhD type to be obtained, uncrossmatched blood 
of the same group as the patient will be provided. On completion of a full group and 
screen, and as long as the patient does not have a red cell antibody, group-specific 
and crossmatch-compatible blood is available. 
If the patient has a red cell antibody, finding compatible blood may be delayed while 
the antibody is identified and antigen-negative red cells selected and crossmatched. 
Under these circumstances, if blood is still urgently required, incompatible red cells 
may have to be used. However the decision to transfuse should be made in discussion 
with a NZBS Transfusion Medicine Specialist/Medical Officer.
Transfusion Medicine Handbook 3rd Edition 
Page 27

3.11  Removal from Storage and Time Limits for Infusion
It is important that blood components are transfused as soon as possible following 
receipt from the blood bank so that the required efficacy is achieved and unwanted 
bacterial proliferation is avoided.
Red Cells
■  
Transfusion should begin as soon as possible following removal of the unit from 
a monitored blood refrigerator or validated transport container.
■  
Transfusion of red cells should be completed within four hours of removal from 
a monitored blood refrigerator or validated transport container.
■  
Where a short delay occurs (or is anticipated) before starting a transfusion, 
red cells may be held at ambient temperature provided the transfusion can be 
completed within four hours of the blood being issued from a monitored blood 
refrigerator. 
■  
If transfusion cannot be started within 30 minutes, the unit should normally be 
returned without delay to a monitored blood refrigerator for controlled storage. 
■  
Red cells must be stored in a refrigerator that is manufactured and validated for 
the purpose of storing red cell components and has permanent temperature 
monitoring. They must not be stored in a ward refrigerator, domestic refrigerator 
or refrigerator intended for vaccine storage.
■  
If a unit of red cells has been out of controlled storage for more than 30 minutes 
and there is no prospect of imminent transfusion it should be returned to the blood 
bank for disposal. The unit cannot be accepted back into blood bank stock.
Platelets
■  
Transfusion should begin as soon as the platelets are received from the blood 
bank. 
■  
Transfusion of platelets should be completed within one hour of issue from the 
blood bank.
■  
If not used immediately, platelets must be returned to the blood bank and 
controlled storage within one hour of issue. 
■  
Platelets are stored (usually in the blood bank) at room temperature 20 - 24ºC 
with constant agitation.
■  
Platelets must not be transported or stored in a refrigerator or chilled transport 
container. 
■  
If platelets have been out of controlled storage for more than one hour, 
acceptance back into blood bank stock is conditional on evidence of suitable 
storage.
Fresh Frozen Plasma
■  
Transfusion should begin as soon as the thawed plasma is received from the 
blood bank.
Page 28 
Transfusion Medicine Handbook 3rd Edition

■  
Transfusion of plasma should be completed within four hours of thawing.
■  
If the plasma is not going to be used or transfusion cannot be started within 
30 minutes it must be returned to the blood bank immediately. If returned within 
30 minutes of issue then it can be stored for up to 24 hours at 2 - 6°C during 
which time it may be reissued to the same or a different patient. If not used 
within 24 hours, the returned plasma expires.
■  
If the plasma has been out of controlled storage for more than 30 minutes it 
cannot be accepted back into blood bank stock.
■  
Once thawed, plasma must not be refrozen.
Cryoprecipitate
■  
Transfusion should be started as soon as the thawed cryoprecipitate is received 
from the blood bank.
■  
Transfusion of cryoprecipitate should be completed within four hours of thawing.
■  
If the cryoprecipitate is not going to be used or transfusion cannot be started 
within 30 minutes it must be returned to the blood bank immediately, where 
it can then be stored for up to 4 hours at ambient (room) temperature during 
which time it may be reissued to the same or a different patient. If not used 
within 4 hours, the returned cryoprecipitate expires.
■  
If the cryoprecipitate has been out of controlled storage for more than 30 minutes 
it cannot be accepted back into blood bank stock.
■  
Once thawed, cryoprecipitate must not be stored in the refrigerator nor should 
it be refrozen.
3.12  Administration and Observation of Transfusion
All transfusions should be performed and monitored in accordance with relevant 
hospital policies and guidelines. The 2011 ANZSBT & Royal College of Nursing of 
Australasia (RCNA) Guidelines for the Administration of Blood Products may provide 
supplementary guidance.
■  
Before transfusion always check the identity of the recipient, that the correct 
blood component or fractionated product has been obtained, and that it has 
not expired.
■  
Transfuse only if the patient can be observed and monitored by trained staff.
3.13  Rate of Infusion and Precautions 
The appropriate rate of transfusion may vary significantly according to the clinical 
circumstances:
■  
Patients who are actively bleeding and/or are in hypovolaemic shock will require 
blood components to be transfused as rapidly as possible.
■  
Patients with cardiac failure are at risk of circulatory overload and it will 
be necessary to transfuse slowly and cautiously with frequent monitoring. 
Concomitant use of diuretics should also be considered.
Transfusion Medicine Handbook 3rd Edition 
Page 29

■  
For fractionated products, the package insert provides guidance on specific 
protocols regarding the administration of the product. 
Advice must be sought from the doctor responsible for the patient if there is any 
doubt about the way or how rapidly a blood component or fractionated product 
should be transfused.
3.14  Infusion Pumps 
Approved infusion pump devices may be used to assist transfusion. Check the 
manufacturer’s instructions before using a pump to transfuse red cells or platelet 
concentrates.
3.15  Blood Administration Sets and Filters
All blood components, including platelets and plasma components, must be transfused 
through a standard sterile blood administration set incorporating a suitable integral 
screen filter (normally 170 - 200 micron pore size). The filter is designed to trap cellular 
aggregates, cellular debris and clots potentially harmful to the patient. Microaggregate 
filters are not indicated.
In New Zealand, bedside leucocyte-depleting filters are not required as all blood 
components undergo prestorage leucodepletion during processing.
Blood administration sets must be used in accordance with the manufacturer’s 
instructions and hospital policy. The following provides a general guide to the use of 
blood administration sets.
Administration sets may be primed with 0.9% sodium chloride (‘normal saline’) or 
the component being transfused. Compound sodium lactate (Hartmann’s or Ringer-
Lactate), Plasmalyte in 5% glucose and dextrose solutions must not be used.
■  
Because of the risk of bacterial proliferation, each administration set should only 
be used for up to 12 hours of transfusion or until the filter becomes clogged. 
■  
One administration set may be used for transfusing up to 4 red cell units provided 
the flow rate remains adequate. 
■  
In a massive transfusion setting, 8 - 10 units may be transfused before the set 
is changed, provided the flow rate remains adequate without evidence of filter 
clogging and the set is changed at least every 12 hours.
■  
Transfuse platelets through a fresh administration set. Transfusing platelets 
through an administration set previously used for red cells is not recommended.
■  
Administration sets should be flushed with normal saline before and after platelet 
transfusion if the same set is to be subsequently used for the transfusion of red 
cells or FFP. 
■  
If there is doubt about the appropriateness of filters or their use, contact the 
blood bank, NZBS Transfusion Medicine Specialist/Medical Officer or NZBS 
Transfusion Nurse Specialist. 
3.16  Warming of Blood Products
If warming is clinically indicated, use only an appropriate and approved system. The 
warming system must be equipped with a visible thermometer and an audible alarm 
Page 30 
Transfusion Medicine Handbook 3rd Edition

as malfunction can result in red cell haemolysis. Blood components must not be 
warmed above 41°C.
Clinical indications for the use of blood warmers:
■  
Large volumes transfused rapidly, for example > 50 mL/kg/hr in adults and 
> 15 mL/kg/hr in children.
■  
Neonatal exchange transfusions.
■  
Trauma situations in which core-rewarming measures are indicated.
■  
Patient rewarming phase during cardiopulmonary bypass surgical procedures.
■  
Transfusions for patients with clinically significant cold reactive antibodies (‘cold 
agglutinins’), i.e., symptomatic cold haemagglutinin disease (CHAD).
Blood warmers are not indicated for routine transfusion of blood. Blood warming is 
seldom necessary or desirable for elective transfusion at conventional rates, even for 
patients with asymptomatic cold agglutinins.
3.17  Compatible Intravenous Solutions
■  
No drugs or additives, other than 0.9 % sodium chloride (‘normal saline’) 
intravenous infusion, are recommended to be mixed with red cells before or 
during transfusion.
■  
Do not use Plasmalyte 148 in 5% glucose or 5% dextrose solutions as these 
may induce haemolysis.
■  
Do not use Gelofusal® or compound sodium lactate solutions, e.g., Hartmann’s 
or Ringer-Lactate, as these contain calcium and may induce clot formation in 
the blood component bag and/or administration set.
3.18  Adding Medication to Blood Components
Do not add medication to any blood component unless specifical y approved by 
hospital policy. If there is doubt, contact a NZBS Transfusion Medicine Specialist/
Medical Officer or NZBS Transfusion Nurse Specialist for advice.
3.19  Documentation of Transfusion
Full and accurate documentation of every step of the transfusion process is vital. Not 
only is this important for effective investigation of serious transfusion-related adverse 
events such as transfusion-transmitted infections, it also facilitates auditing of al  
aspects of the transfusion process and is essential in ensuring vein-to-vein traceability of 
blood components and fractionated products. Table 3.1 summarises the requirements 
of documentation associated with transfusion.
The majority of transfusion errors are administrative or clerical. Common errors include:
■  
Failure to identify the patient properly when taking pretransfusion blood samples.
■  
Failure to correctly label the patient’s pretransfusion blood sample at the bedside.
■  
Transcription errors in the laboratory.
■  
Failure to clearly identify the intended recipient prior to transfusion.
Transfusion Medicine Handbook 3rd Edition 
Page 31

Table 3.1:  Documentation of Transfusion
Requirement
Action
Prescription
Constitutes the legal instruction (from the medical practitioner, 
registered midwife or nurse practitioner) to administer blood 
components and fractionated products and must be placed 
in the patient’s medical record. The prescription must be 
legibly written, be dated and include the prescriber’s name 
and signature. The prescription must specify:
■ 
blood component / fractionated product to be administered
■ quantity
■ 
route of administration
■ 
rate of infusion  
■ 
any special requirements
Justification for 
Document the transfusion decision (based on recognised 
transfusion
clinical practice guidelines) in the patient’s medical record.
Informed consent
Must be obtained from the patient and documented (in the 
medical record) except in emergencies where appropriate 
communication is not possible.
Patient’s medical 
■ 
Prescription of the blood component / fractionated product.
record
■ 
Evidence of informed consent.
■ 
The compatibility label (or other labelling with patient and 
blood component / fractionated product details), which 
should be removed after completing the transfusion and 
attached to the transfusion record.
■ 
Evidence of the bedside checking procedure.
■ 
Vital signs during the transfusion.
■ 
The indication for the use of the blood component / 
fractionated product.
■ 
The date of transfusion and the time transfusion started 
and finished.
■ 
The number and type of blood components / fractionated 
products (including the donation / batch numbers).
■ 
Whether or not the desired effect was achieved.
■ 
A record of the occurrence and management of any 
transfusion-related adverse event.
Retention of 
■ 
 In accordance with statutory requirements, namely the 
records
Health (Retention of Health Information) Regulations 1996
amended by section 111(2) of the New Zealand Public 
Health and Disability Act 2000, records of transfusion 
must be retained for a minimum of 10 years.
3.20  Local Systems and Procedures
It is important to be familiar with local hospital policies in regard to transfusion practices. 
Visiting the blood bank may also be useful in gaining an appreciation of the local system 
for obtaining blood components and fractionated products and meeting the clinical, 
nursing and scientific staff who provide transfusion services. There is no substitute for 
talking with people who are working to help you care for your patients.
Page 32 
Transfusion Medicine Handbook 3rd Edition

3.21  Reporting of Adverse Events
If the patient experiences a reaction as a result of transfusion, has received an 
inappropriate transfusion, received a blood component or fractionated product 
intended for another patient or where special requirements (for example, irradiated 
components) are not met, these are regarded as transfusion-related adverse events. 
Transfusion reactions can cause a patient’s condition to rapidly deteriorate with 
respiratory distress, hypotension and collapse. Any signs or symptoms suggesting a 
reaction should not be ignored, but rather assessed immediately.
Any untoward reaction or event occurring during or after the transfusion must be 
reported immediately to the blood bank and serious events (life-threatening or with 
a risk of major morbidity) should also be reported to a NZBS Transfusion Medicine 
Specialist/Medical Officer or NZBS Transfusion Nurse Specialist. 
Adverse effects of transfusion and the reporting of events is covered in detail in Chapter 
7: Adverse Effects of Transfusion.
Transfusion Medicine Handbook 3rd Edition 
Page 33

4
BLOOD COMPONENTS
Blood components are made from blood donations and may involve one or more 
simple physical processing steps to separate the constituents of blood.
The entries in this section are summaries of information presented in the NZBS Clinical 
Compendium
, which is a source of reference for the clinical activities of NZBS. The 
compendium provides a framework for clinicians on the nature, composition and clinical 
use of the components and contains detailed individual component descriptions, 
quality specifications, storage requirements, dosage and administration guidelines, 
precautions and contraindications to use, along with information on potential adverse 
reactions.
The compendium is a controlled document. Regular updates of the individual 
documents it contains are produced and disseminated to holders. Documents within 
the compendium can also be found in the Clinical Information section of the NZBS 
website (www.nzblood.co.nz).
4.1 
ABO Blood Groups and Antibodies 
ABO is the most important of the human blood group systems. There are four different 
ABO blood groups, determined by whether or not an individual’s red cells carry one, 
both or neither of the A and B antigens. 
Normal healthy individuals, from early childhood, make red cell antibodies against the 
A or B antigens that are not expressed on their own cells. These naturally occurring 
antibodies are mainly IgM immunoglobulins and can rapidly bind to and destroy red 
cells carrying the corresponding antigen. 
If ABO incompatible red cells are transfused, intravascular haemolysis of these red 
cells can occur. An ABO incompatible transfusion reaction may result in overwhelming 
disruption of haemostatic equilibrium and complement activation, resulting in shock 
and renal failure. This can be fatal, even after transfusion of a small volume of 
incompatible blood.
Table 4.1: ABO Blood Groups and Antibodies
Patient’s ABO 
Red Cell ABO  
Plasma ABO 
Blood Group
Antigens
Antibodies
A
A
Anti-B
B
B
Anti-A
AB
A and B
None
O
None
Anti-A and Anti-B
4.2 
Avoiding ABO Incompatible Transfusions 
Safe transfusion depends on avoiding ABO incompatibility between the patient and 
transfused blood components, either between donor red cells and the patient’s ABO 
antibodies or conversely donor plasma ABO antibodies and the patient’s red cells. 
Page 34 
Transfusion Medicine Handbook 3rd Edition

Red cells of the same ABO group as the patient, i.e., ABO identical, should normally 
be selected. Only when these are unavailable should alternative ABO compatible red 
cells be selected (see Table 4.9: ABO Compatibility for Red Cell Components). In life-
threatening situations, where a confirmed blood group for the patient is not available, 
group O red cells should be given. Group O donations identified as emergency units 
have low levels of anti-A and anti-B to avoid potential sensitisation and destruction of 
the patient’s red cells (in non-group O recipients).
Platelet concentrates should ideally be ABO identical or alternatively ABO compatible 
with the patient’s red cells (see Table 4.11: ABO Compatibility for Platelet Components). 
This is however not a strict requirement and, due to logistics or supply issues, platelets 
with a different ABO group may be supplied in clinically urgent situations following 
consultation with an NZBS Transfusion Medicine Specialist. Additional pretransfusion 
testing is not required for platelets.
Fresh frozen plasma and cryoprecipitate should be ABO compatible with 
the patient’s red cells (see Table 4.14: ABO Compatibility of Fresh Frozen Plasma 
and Cryoprecipitate
). Additional pretransfusion testing is not required for FFP and 
cryoprecipitate.
4.3 
RhD Antigen
After ABO, the RhD antigen ranks next in importance for transfusion. Patients and 
blood donors are routinely typed for the RhD antigen and on the basis of its presence 
or absence are called either RhD positive or RhD negative.
Antibodies to the RhD antigen only occur as a result of transfusion or pregnancy in 
individuals who are RhD negative. The RhD antigen is highly immunogenic and a RhD 
negative person only needs to be exposed to a small volume of RhD positive red cells 
for immunisation to occur, stimulating production of anti-D. 
Red cell and platelet transfusions are normally of the same RhD type as the patient. 
RhD negative components may be given to RhD positive recipients without any risk 
of immunisation. 
In life-threatening situations or where RhD identical components are not readily 
available, it may be necessary to transfuse RhD negative recipients with red cells or 
platelets from a RhD positive donor. In these circumstances the blood bank will provide 
guidance. It is essential that the treating clinician is informed and the appropriateness 
of administration of prophylactic anti-D immunoglobulin considered. In the case of RhD 
negative females with child-bearing potential, transfusion of RhD positive red cells must 
only be considered following discussion with a NZBS Transfusion Medicine Specialist. 
If supplies of RhD negative red cells are low, RhD positive red cells may be provided 
by the blood bank for RhD negative males and for females beyond reproductive years.
Residual red cells in RhD positive platelet components may sensitise RhD negative 
patients to form anti-D. When platelet components from a RhD positive donor are 
transfused into a RhD negative recipient, in particular females of childbearing age or 
female children, prophylactic anti-D immunoglobulin must be considered. 
Section 5.4.7: Rh(D) Immunoglobulin-VF contains guidelines on dosing of prophylactic 
anti-D following transfusion of RhD positive blood components.
Transfusion Medicine Handbook 3rd Edition 
Page 35

4.4 
Other Blood Group Systems
Red cells possess many different antigens. Transfusion or pregnancy can stimulate 
antibody production where a person is exposed to a red cell antigen that they lack. 
Some of these antibodies can cause transfusion reactions or haemolytic disease of 
the fetus and newborn (HDFN). Before transfusion and during pregnancy it is important 
to detect clinically significant antibodies in a patient so that compatible red cells can 
be provided and appropriate advice given during pregnancy. 
4.5 
Cytomegalovirus (CMV)
Prior to the introduction of routine prestorage leucodepletion, CMV was readily 
transmitted by transfusion. CMV can cause severe and even fatal disease in certain 
immunocompromised patients not previously exposed to the virus. Such patients 
should receive CMV ‘safer’ blood components, i.e., components that have undergone 
prestorage leucodepletion or found to be CMV-antibody negative.
The use of either prestorage leucodepletion or selection of CMV-antibody negative 
blood components, obtained from a regular donor who has donated at least once in 
the preceding 6 months, significantly reduces the risk of CMV transmission and CMV 
disease in susceptible recipients. However, neither method alone or in combination 
can completely avoid transmission from the occasional donor with CMV viraemia in 
the “window” period prior to the development of antibodies following acute infection 
or when reactivation of latent infection occurs.
Since all blood components in New Zealand are leucodepleted, NZBS has adopted 
a policy that restricts the requirement for the use of blood components from CMV-
antibody negative donors to:
■  
Intrauterine and neonatal transfusion.
■  
A selected individual patient following discussion and agreement between the 
treating clinician and a NZBS Transfusion Medicine Specialist.
4.6 Irradiation
Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but usually fatal 
complication of transfusion. The risk associated with an individual transfusion depends 
on the number and viability of contaminating lymphocytes, the susceptibility of the 
patient’s immune system to donor lymphocyte engraftment (primarily related to the 
degree of T-cell immunosuppression) and the degree of immunological incompatibility 
between donor and patient. 
Cellular components, with the exception of thawed cryopreserved haematopoietic 
progenitor cells (HPC) intended for transplantation, must be irradiated to prevent 
TA-GVHD in at-risk patients. Frozen plasma components and fractionated products 
do not require irradiation.
The following tables summarise the clinical indications for blood component irradiation 
recommended by the 2011 Australian & New Zealand Society of Blood Transfusion 
(ANZSBT)  Guidelines for Prevention of Transfusion-Associated Graft-Versus-Host 
Disease
 and the 2010 BCSH Guidelines on the Use of Irradiated Blood Components. 
Page 36 
Transfusion Medicine Handbook 3rd Edition

Table 4.2: Definite Clinical Indications for Use of Irradiated Blood Components
Directed donations (from blood relatives)
HLA selected/matched platelet transfusions
Granulocyte transfusions
Intrauterine and all subsequent neonatal exchange transfusions
Congenital cellular immunodeficiency disorders
Allogeneic and autologous haematopoietic stem cell transplantation (HSCT)
Hodgkin lymphoma
Purine nucleoside analogues and the related agent bendamustine1 for malignant or 
non-malignant disorders
Alemtuzumab for malignant or non-malignant disorders
1Bendamustine combines the alkylating properties of mechlorethamine and the purine antimetabolite 
properties of benzimidazole.

Table 4.3: Possible Clinical Indications for Use of Irradiated Blood Components
Premature infants and infants weighing less than 1300g
All newborn infants
Acute leukaemia
Non-Hodgkin lymphoma
Patients with B-cell malignancy who receive non-nucleoside analogue containing 
chemotherapy and/or radiotherapy leading to lymphopenia < 0.5 x109/L
T-cell malignancy
Patients receiving high doses of chemotherapy and/or irradiation sufficient to cause 
lymphopenia < 0.5 x109/L
Patients receiving long term or high dose steroids as therapy for malignant disorders
Aplastic anaemia receiving immunosuppressive therapy
Massive transfusion for trauma
Table 4.4: No Clinical Indication for Use of Irradiated Blood Components
HIV/AIDS (where none of the above listed indications apply)
Congenital humoral deficiency disorders
Solid organ transplantation 
Transfusion Medicine Handbook 3rd Edition 
Page 37

Table 4.5: Recommendations on Duration of Use of Irradiated Blood Components
Autologous HSCT
From 7 days prior to initiation of conditioning and until at least three months post-
autograft, or six months if total body irradiation (TBI) is used.
Allogeneic HSCT
From initiation of conditioning and continued while post-transplant GVHD prophylaxis 
is given, for a minimum of 6-12 months or until lymphocytes > 1x109/L. Patients 
with active chronic post-transplant GVHD should continue to receive irradiated 
components.
Aplastic anaemia treated with ATG immunosuppression
From initiation of therapy. No clear recommendations as to duration, but possibly until 
lymphocytes > 1x109/L.
Hodgkin lymphoma
At all stages of disease and therapy. Continued indefinitely.
Purine nucleoside analogues1 and bendamustine
From initiation of therapy. Continued indefinitely.
Alemtuzumab
From initiation of therapy. No clear recommendations as to duration, but at least 12 
months from last dose.
1Fludarabine, deoxycoformycin (pentostatin), chlorodeoxyadenosine (cladribine) and clofarabine.
Page 38 
Transfusion Medicine Handbook 3rd Edition

esh is 
e issued in this 
educed by blood loss or 
ease tissue oxygenation 
ed cells ar
Indication for Use / Comments 
irtually all r
Used to incr
when critically r
anaemia
V
form
As for Red Cells Resuspended
Not suitable for large volume transfusion 
or exchange transfusion
Potassium content, when fr
2.0 mmol/L, and at expiry 15-35 
mmol/L (may be raised if component is 
irradiated)
Must be irradiated
 
 
 
 
Expiry
35 days 
(2 - 6°C)
35 days 
(2 - 6°C)
5 days 
(2 – 6°C) 
24 hrs once 
irradiated
0.50 - 0.70
0.50 - 0.70
0.75 - 0.90
Haematocrit  (%)
298
70
206
Typical Mean  Volume (mL)
< 5 
om NZBS
es of 
es of 
om whole 
vailable from NZBS
ed fr
vailable fr
eplaced by additive 
epar
ed to specified haematocrit 
ed cell antibodies)
emoval of plasma 
esh whole blood donation (
epar
Description
Red cells pr
blood donation with plasma 
removed and r
solution
As for Red Cells Resuspended
Split into equal volume aliquots 
suitable for neonatal use 
CMV negative 
Does not contain high titr
anti-A or anti-B
Fr
days old) collected into CPD and 
pr
by r
CMV negative 
Does not contain high titr
anti-A or anti-B (also negative for 
other r
Blood Components A
 
4.7

Table 4.5: Red Cell Components A
Component
Red Cells 
Resuspended
Red Cells 
Resuspended 
Neonatal
Red Cells For 
IUT
Transfusion Medicine Handbook 3rd Edition 
Page 39


oduct 
cuit in 
e the infant has 
e indicated
educed by blood loss or 
eceived IUT 
ease tissue oxygenation 
diac bypass cir
esponse to persistent allergic 
ed cells ar
ement only wher
oduct of choice for neonatal exchange 
eviously r
Indication for Use / Comments 
Pr
transfusion 
Exchange transfusion for clinically 
significant anaemia with or without 
hyperbilirubinaemia due to haemolytic 
disease of the fetus and newbor
(HDFN) or other causes 
Should be irradiated if for neonatal 
exchange transfusion, although a strict 
requir
pr
Can also be used for large volume 
transfusions in neonates and for adult 
transfusions 
Used in r
reactions, for some IgA deficient 
patients with anti-IgA, and when anti-T 
depleted r
Restricted access to this pr
Used to incr
when critically r
anaemia
Primary car
paediatric bypass surgery
 
 
 
 
 
 
 
 
 
 
Expiry
5 days 
(2 - 6°C) 
for neonatal 
exchange 
transfusion
28 days 
(2 - 6°C) 
for other 
uses
24 hrs 
(2 - 6°C)
CPD-A1: 35 
days 
(2 - 6°C)
CPD: 28 
days 
(2 - 6°C)
0.45 - 0.55
0.40 - 0.70
0.30 - 0.50
Haematocrit  (%)
360
328
493
Typical Mean  Volume (mL)
ed to 
epar
emoval 
es of 
otein 
ected donations 
vailable from NZBS continued
esidual plasma pr
e issued in this form
Description
Whole blood donation pr
specified haematocrit by r
of plasma
CMV negative
Does not contain high titr
anti-A or anti-B
Red cell donation washed leaving 
total r
< 0.5 g per unit
Resuspended in additive solution
Whole blood donation collected 
into CPD or CPD-A1
Autologous and dir
ar
 
ashed
Component
Whole Blood 
Plasma 
Reduced
Red Cells 
W
Whole Blood
Table 4.5: Red Cell Components A
Page 40 
Transfusion Medicine Handbook 3rd Edition

ded at the 
om whom it 
ed for 
e deficiency of 
oblem
A or HLA antibodies 
esponse
ovides an adequate clinical 
eased platelet consumption 
ovide compatible platelets for 
efractory to random donor 
ith incr
Indication for Use / Comments 
Replacement wher
platelets or platelet dysfunction is 
causing or may cause a significant 
haemostatic pr
One unit pr
response in most adult patients
W
or destruction the dose is determined 
by the clinical r
As for Platelet Pool
Also to pr
patients with HP
and r
platelets
Indication for Use / Comments 
Unit is labelled and stor
transfusion to the patient fr
was collected. If not transfused to the 
identified patient, unit is discar
designated expiry of the component
 
 
 
Expiry
Expiry
7 days
(20 - 24°C 
with constant 
agitation) 
If irradiated 
original expiry 
applies
As for Platelet 
Pool
 
)9
(x 10
■≥240
≥240
Platelets 
Haematocrit  (%)
307
228
Typical  Mean 
Typical Mean  Volume (mL)
Volume (mL)
esis 
om the 
vailable from NZBS continued
vailable from NZBS
AS)
om a single apher
AS)
ements the same as Whole 
fy coats of four whole blood 
Description
Platelet pool derived fr
buf
donations
Resuspended in platelet additive 
solution (P
Platelets fr
donation
Resuspended in platelet additive 
solution (P
Description
Specifications and storage 
requir
Blood
esis
Component
Whole Blood 
Autologous
Table 4.5: Red Cell Components A
Table: 4.6: Platelet Components A
Component
Platelet Pool
Platelets 
Apher
Transfusion Medicine Handbook 3rd Edition 
Page 41

eactions to 
e allergic r
ent sever
Indication for Use / Comments 
As for Platelet Pool
May be indicated in patients who have 
recurr
plasma-containing components and 
in some IgA deficient patients with 
anti-IgA antibodies
 
 
 
 
Expiry
As for Platelet 
Pool
Closed 
system: 
24 hrs
(20 - 24°C 
with constant 
agitation)
Open system: 
6 hrs
(20 - 24°C 
with constant 
agitation)
 
)9
(x 10
≥40
■≥240 
Platelets 
45
227
Typical  Mean 
Volume (mL)
esis 
otein 
vailable from NZBS continued
esis donation 
om a single apher
esidual plasma pr
oved platelet additive 
Description
Single apher
suspended in plasma
Divided into equal volume aliquots 
suitable for neonates
CMV negative
Platelets fr
donation, washed with an 
appr
solution. 
Total r
< 0.5 g per unit.
esis
esis 
ashed
Component
Platelets 
Neonatal 
Apher
Platelets 
Apher
W
Table: 4.6: Platelet Components A
Page 42 
Transfusion Medicine Handbook 3rd Edition

e is 
■ 
e ther
ed to 
d adult 
openia 
esponding 
ecovery of 
equir
/L, bone 
fy coats 
9
Comments
ow hypoplasia and 
ow function
esis granulocytes
Indication for Use / 
ofound neutr
Supportive therapy for 
pr
<0.5 x 10 marr infection not r to antibiotics within 48  hours, and wher potential for r marr
Irradiate prior to use 
Clinical indications as for 
apher
Multiple buf
≥10 will be r achieve a standar therapeutic
 
 
esis
Expiry
24 hrs 
(20 - 24°C)
As for 
Granulocyte 
Apher
 
)9
(x 10
≥ 200
  ≥ 50
Platelets 
 
)9
(x 10
≥10
  ≥ 1
Granulocytes
50
Variable
Typical Mean  Volume (mL)
vailable from NZBS
om 
om a 
esis 
ed cells and 
ed cells 
Description
Granulocytes (with 
some r
platelets) fr
single apher
donation 
CMV negative if 
indicated
Granulocytes (with 
some r
and platelets) fr
single whole blood 
donation 
esis
fy Coat
Table 4.7: Granulocyte Components A
Component
Granulocyte 
Apher
Buf
Transfusion Medicine Handbook 3rd Edition 
Page 43

educed
ozen
oteins when 
e critically r
esh Fr
Indication for Use/Comments
Replacement of coagulation factors 
and other plasma pr
levels or activity ar
As for Plasma Fr
 
eeze
 
 
efr
ozen
esh Fr
Expiry 
24 months 
(-25°C or below)
24 hrs post 
thawing 
(2 - 6°C)
Do not r
As for Plasma 
Fr
(g)
Mean 
Fibrinogen 
 

Factor  VIIIc 
≥ 0.7
(IU/mL)
  ≥ 0.7
279
60
vailable from NZBS
Typical Mean  Volume (mL)
esis 
om 
e fr
ozen
es of anti-A 
ocedur
esh Fr
Description
Plasma collected 
using an apher
pr
a male donor (to 
reduce the risk 
of TRALI), rapidly 
frozen within 8 
hours of collection 
to maintain labile 
coagulation 
factors
As for Plasma 
Fr
Split into equal 
volume aliquots 
suitable for 
neonates
Does not contain 
high titr
or anti-B
esh 
esh 
ozen
ozen Neonatal
Table 4.8: Frozen Plasma Components A
Component
Plasma Fr
Fr
Plasma Fr
Fr
Page 44 
Transfusion Medicine Handbook 3rd Edition

eating 
illebrand 
eatment of 
ombocytopenic 
eat von W
opriate or unavailable can 
ombotic Thr
ect haemostatic defects 
Indication for Use/Comments
Used for plasma exchanges 
particularly in the tr
Thr
Purpura (TTP)
Corr
associated with fibrinogen deficiency 
and dysfibrinogenaemia
May be of clinical value for tr
bleeding due to uraemia
If specific concentrate therapy is 
inappr
be used to tr
disease, haemophilia A or factor XIII 
deficiency
 
 
oom 
e)
eeze
ozen
efr
ed at r
esh Fr
Expiry 
As for Plasma 
Fr
24 months 
(-25°C or below) 
4 hrs post thawing
(stor
temperatur
Do not r
(g)
1.2
Mean 
Fibrinogen 
 

Factor  VIIIc  (IU/mL)
  ≥ 1.5
473
98
Typical Mean  Volume (mL)
vailable from NZBS continued


esis 
esis 
om 
esh 
e fr
natant 
ecipitate 
ce of 
ozen depleted 
illebrand factor
onectin
ocedur
illebrand factor
onectin 
Description
Super
from apher
cryopr
frozen within 2 
hours of collection
Plasma Fr
Fr
of fibrinogen, 
factor VIII, von 
W
factor XIII, and 
fibr
Plasma collected 
using an apher
pr
a male donor (to 
reduce the risk of 
TRALI)
Concentrated 
sour
fibrinogen, 
factor VIII, von 
W
factor XIII, and 
fibr
esis 
ecipitate 
esis - High 
Component
Plasma 
Cryodepleted 
Apher
Cryopr
Apher
Fibrinogen
Table 4.8: Frozen Plasma Components A
Transfusion Medicine Handbook 3rd Edition 
Page 45

4.8 
Red Cell Components
ABO Compatibility 
It is important that transfusion recipients receive red cell components compatible with 
their own ABO group. Incompatible transfusion can result in serious harm or death 
of the recipient.
It is best practice to transfuse donor red cells that are matched for the recipient. In some 
circumstances it may not be possible to transfuse the recipient with donor cells of the 
same group. The following table outlines alternative donor groups that may be given to 
a recipient if supplies of ABO identical red cells are not available or are in short supply.
Table 4.9: ABO Compatibility for Red Cell Components
Recipient 
Compatible Donor Groups  
Group
(in order of preference)
Unknown
Group O§ cells 
Preferably RhD negative for premenopausal females 
The transfusion of group O cells is usually continued only until the 
patient’s blood group is known
O
O
A
A or O
B
B or O
AB
AB or A or B or O§
§These group O components should test negative for ‘high titre’ anti-A and anti-B.
RhD Compatibility 
Red cell and platelet transfusions are normally of the same RhD type as the patient. 
RhD negative components may be given to RhD positive recipients without any risk 
of immunisation. 
In life-threatening situations it may be necessary to transfuse RhD negative recipients 
with RhD positive red cells. In these circumstances the blood bank will provide 
guidance. It is essential that the treating clinician is informed and the appropriateness 
of administration of prophylactic anti-D immunoglobulin considered. 
If supplies of RhD negative red cells are low, RhD positive red cells may be provided 
by the blood bank for RhD negative males and for females beyond reproductive years.
In the case of RhD negative females with child-bearing potential, transfusion of RhD 
positive red cells must only be considered following discussion with a NZBS Transfusion 
Medicine Specialist. 
Section 5.4.7: Rh(D) Immunoglobulin-VF contains guidelines on dosing of prophylactic 
anti-D following transfusion of RhD positive components.
Guidelines for Appropriate Use
In deciding whether or not to transfuse red blood cells, the haemoglobin level, although 
important, should not be the sole deciding factor. Patient factors, signs and symptoms 
Page 46 
Transfusion Medicine Handbook 3rd Edition

of hypoxia, ongoing blood loss, the degree of urgency required in correcting the 
anaemia and the risk of transfusion-related adverse effects should all be considered. 
The key issue is delivery of adequate amounts of oxygen to tissues. For a 70-80 
kg patient, a transfusion of 4-5 mL/kg will increase the circulating haemoglobin by 
about 10 g/L. 
Some specific factors to consider before deciding to transfuse:
■  
Cardiopulmonary reserve 
 
If cardiac or pulmonary function is not normal, it may be necessary to consider 
transfusing at a higher haemoglobin level.
■  
Volume of blood loss 
 
Clinical assessment should attempt to quantify the volume of blood loss before, 
during, and after surgery, to ensure maintenance of adequate blood volume.
■  
Oxygen consumption 
 
This may be affected by a number of factors including fever, anaesthesia, 
shivering and thyrotoxicosis. If oxygen consumption is increased it may be 
necessary to consider transfusing at a higher haemoglobin level.
■  
Atherosclerotic disease  
Critical arterial stenosis to major organs, particularly the heart, may modify 
indications for the use of red cells.
The Australian National Blood Authority (NBA) Patient Blood Management Guidelines 
and the 2012 British Committee for Standards in Haematology (BCSH) Guidelines on 
the Management of Anaemia and Red Cell Transfusion in Adult Critically Ill Patients 
provide the following recommendations for red cell component use in adults. 
Table 4.10: Indications for Transfusion of Red Cells in Relation to Haemoglobin Level
Hb Level
Indication
< 70 g/L
Transfusion of red cells is usually indicated however a lower 
threshold may be acceptable in patients without symptoms and 
where specific therapy is available, e.g., cobalamin or iron deficiency 
anaemia.
< 80 g/L 
Transfusion of red cells is likely to be appropriate in patients 
with acute coronary syndrome and the haemoglobin should be 
maintained > 80-90 g/L.
70 - 100 g/L 
Transfusion of red cells is likely to be appropriate during surgery 
associated with major blood loss or with evidence of impaired tissue 
oxygen delivery.
> 90 g/L 
Transfusion of red cells is not likely to be appropriate in the critically 
ill, in whom a restrictive transfusion policy is associated with 
reduced mortality. Exceptions may include patients with any of the 
following: sepsis together with evidence of impaired tissue oxygen 
delivery, subarachnoid haemorrhage, ischaemic stroke, and cerebral 
ischaemia complicating traumatic brain injury.
> 100 g/L
Transfusion of red cells is not likely to be appropriate unless there 
are specific indications.
Transfusion Medicine Handbook 3rd Edition 
Page 47

Restrictive Red Cell Transfusion Policy
The decision to transfuse should take into account the risks, benefits and alternatives 
available, and should not be based on haemoglobin level alone. With this in mind, 
increasingly restrictive transfusion policies are being implemented in a variety of 
clinical settings. 
Policies aim to safely provide the minimum amount of blood required for an individual 
patient through setting appropriate transfusion triggers and, where indicated, 
encouraging assessment of the patient’s clinical status after transfusion of each single 
unit of red blood cells before determining that further transfusion is required. Restrictive 
policies are supported by evidence from a number of clinical areas of improved or 
equivalent clinical outcomes after minimising exposure to allogeneic blood. 
One such policy, the 2014 Australian NBA Single Unit Transfusion Guide (available 
at http://www.blood.gov.au/single-unit-transfusion), has been designed for use in 
stable, normovolaemic adult patients, in an inpatient setting, who do not have clinically 
significant bleeding.
4.9 
Platelet Components
ABO and RhD Compatibility 
Transfused platelets should ideally be the same ABO and RhD type as the recipient 
although platelet stocks may not always permit this. Preferably platelet components 
that are ABO/RhD compatible but plasma incompatible should be selected for 
transfusion. This compromise is relatively free of adverse reactions although antibodies 
in the plasma may occasionally cause a haemolytic reaction or a transiently positive 
direct antiglobulin test (DAT). 
Table 4.11: ABO Compatibility for Platelet Components#
Recipient 
Compatible Donor Groups  
Group
(in order of preference)
Unknown
Group O§ or A platelets
Preferably from RhD negative donor for premenopausal females 
O
O or A
A
A or O§
B
B or O§
AB
AB or A or B or O§
#NZBS routinely makes platelet components from group A and O donors only. 
§These group O components should test negative for ‘high titre’ anti-A and anti-B.

In the event of life-threatening bleeding, ABO and/or RhD incompatible platelet 
components may be transfused. 
Rh antigens are not expressed on platelets and RhD incompatibility has no effect 
on the survival of transfused platelets. Residual red cells in RhD positive platelet 
components may however sensitise RhD negative patients to form anti-D. When 
platelet components from a RhD positive donor are transfused into a RhD negative 
Page 48 
Transfusion Medicine Handbook 3rd Edition

recipient, and in particular females of childbearing age or female children, administration 
of prophylactic anti-D immunoglobulin must be considered. Section 5.4.7: Rh(D) 
Immunoglobulin-VF
 contains guidelines on dosing of prophylactic anti-D following 
transfusion of RhD positive blood components.
Clinical Indications
The 2006 BCSH Guidelines on the Management of Massive Blood Loss and the 
Australian NBA Patient Blood Management Guidelines along with expert consensus 
opinion provide the following recommendations for platelet component use in adults.
Table 4.12: Clinical Indications for Use of Platelets
Indication
Management
Chemotherapy-induced  ■    Prophylactic platelets are indicated in patients when 
Bone Marrow Failure
the platelet count is <10 x 109/L in the absence of 
risk factors.
■  
 Prophylactic platelets are indicated in patients when 
the platelet count is <20 x 109/L in the presence of 
risk factors for systemic haemostatic failure such as 
fever or minor bleeding.
Surgery/Invasive 
■  
 Patients with a platelet count  ≥50 x 109/L can 
Procedure
generally undergo invasive procedures without 
serious bleeding; lower counts may be tolerated in 
certain clinical situations. 
■  
 For surgical procedures with high risk of bleeding 
(e.g., ocular or neurosurgery) it may be appropriate 
to maintain the platelet count ≥100 x 109/L.
Platelet Function 
■  
 Rarely require platelet transfusion. May be 
Disorders
appropriate in inherited or acquired disorders.
■  
 The platelet count is not a reliable indicator of platelet 
haemostatic function (e.g., following extended cardiac 
bypass surgery of more than 2 hours duration or 
administration of anti-platelet medications).
■  
 Alloimmunisation to missing glycoproteins may occur 
if platelets are given to patients with certain inherited 
functional defects.
Bleeding
■  
 May be appropriate in any patient in whom 
thrombocytopenia is considered to be a major 
contributing factor.
■  
 In critically ill patients, in the absence of bleeding, 
prophylactic platelet transfusion to prevent bleeding 
may be appropriate at a platelet count <20 x 109/L. 
■  
 In non-critically ill medical patients, lower platelet 
counts may be tolerated. 
■  
 In patients with chronic marrow failure syndromes, 
prophylactic platelet transfusions may lead 
to alloimmunisation and subsequent platelet 
refractoriness.
Transfusion Medicine Handbook 3rd Edition 
Page 49

Table 4.12: Clinical Indications for Use of Platelets continued
Indication
Management
Massive Haemorrhage/
■  
 To adequately maintain the platelet count >50 x 109/L 
Massive Transfusion
while allowing for a margin of error, a transfusion 
trigger of 75 x 109/L is recommended. 
■  
 The platelet count should be maintained >100 x 109/L 
in the presence of diffuse microvascular bleeding, 
multiple or CNS trauma, or platelet dysfunction.
■  
 Massive transfusion protocols, recognising that a 
platelet count <50 x 109/L can be expected after 
replacement of 2 x blood volume, empirically include 
platelet concentrates. Regular laboratory and/or 
point-of-care monitoring may identify patients likely 
to benefit from additional platelet transfusion.
Patients Refractory to Platelet Transfusion
A proportion of patients become refractory to random platelet transfusions. When 
a platelet transfusion fails to achieve the desired response it is important to find 
out whether the failure is due to rapid immunological or non-immunological platelet 
consumption. Clinical factors such as sepsis, disseminated intravascular coagulation 
(DIC), and splenomegaly are more common than alloimmunisation as the cause of 
platelet refractoriness. 
Identifying patients with antibodies to human leucocyte antigens (HLA) or human 
platelet antigens (HPA) is important since the use of HLA- or HPA-matched platelet 
components may result in improved transfusion response. 
In deciding how to treat a refractory patient there may be a number of appropriate 
strategies for improving the response to platelet transfusions such as matching for 
HLA or HPA, increasing the transfused dose or even discontinuing transfusion. 
NZBS has produced Guidelines for the Management of Patients Refractory to Platelets 
from which the table below is taken. These guidelines can be found in the Clinical 
Information
 section of the NZBS website (www.nzblood.co.nz).
Table 4.13: Options for Managing Patients Refractory to Platelets
Indication
Management
Patient’s HLA type not 
■  
 Consider transfusing ABO compatible, single 
known and serum sample(s) 
donor platelets (preferably ‘double-dose’).
not yet available
Patient serum samples 
■  
 Platelets from the donation inventory can be 
available but HLA type not 
prospectively crossmatched and compatible 
known 
units selected for transfusion, although this is 
not the preferred option.
Patient’s HLA type is known,  ■    Consider transfusing HLA-matched platelets 
and HLA-matched platelets 
prior to the completion of antibody testing, as 
are available
HLA immunisation is the most common cause 
of immune refractoriness.
Page 50 
Transfusion Medicine Handbook 3rd Edition

Table 4.13: Options for Managing Patients Refractory to Platelets continued
The patient has HLA and/or 
■  
 Antigen negative (compatible) platelets should 
HPA antibodies
be selected for transfusion. 
■  
 Further antibody testing is recommended every 
3 months or if refractoriness returns.
The patient does not have 
■  
 Consideration should be given to non-
HLA or HPA antibodies
immunological causes for which a 
haematologist or NZBS TMS/MO will advise 
management options.
Matched platelets are prepared for a specific recipient after consultation with a NZBS 
Transfusion Medicine Specialist. They normally require at least 48 hours notice, as, in 
addition to usual pre-release testing for bacterial contamination, suitable donors first 
need to be identified and then bled.
Contraindications 
Transfusion of platelets is generally contraindicated in the following conditions: 
■  
Thrombotic thrombocytopenic purpura (TTP)
■  
Haemolytic uraemic syndrome (HUS)
■  
Heparin-induced thrombocytopenia (HIT)
■  
Posttransfusion purpura (PTP)
Severe adverse reactions have been reported in patients with TTP and HIT following 
platelet transfusion. Platelet transfusion to these patients may also precipitate 
thrombotic events and can aggravate their clinical condition.
In this next group, platelet transfusion is unlikely to cause any sustained increase of 
platelet count:
■  
Immune thrombocytopenic purpura (ITP)
■  
Drug-induced thrombocytopenia of immune origin
Prophylactic use of platelet transfusion in these patients is of little benefit but 
platelet transfusion may be useful to stop active bleeding. These complex disorders 
of haemostasis should be managed in consultation with, or supervised by, a 
haematologist.
Adverse Reactions
Adverse reactions to platelets are predominantly allergic or febrile non-haemolytic 
transfusion reactions. The frequency of adverse reactions during transfusion of platelet 
concentrates has reduced following the introduction of platelet additive solution (PAS) 
as suspension medium.
4.10  Granulocyte Components
Granulocyte components may by collected by apheresis or harvested from buffy coats 
obtained from whole blood donations. Granulocytes must be ABO and RhD compatible 
with the recipient and must be irradiated before transfusion.
Transfusion Medicine Handbook 3rd Edition 
Page 51

NZBS has produced a Policy for Collection and Transfusion of Granulocytes available 
in the Clinical Information section of the NZBS website (www.nzblood.co.nz).
A request for granulocyte components must be made in consultation with a NZBS 
Transfusion Medicine Specialist.
Clinical Indications
The literature has shown granulocyte transfusions may be beneficial and even life-saving 
in severely neutropenic patients with systemic bacterial or invasive fungal infections 
not responding to antimicrobial therapy after 24 to 48 hours, and in whom there is 
the potential for recovery of marrow function.
The literature on prophylactic granulocyte transfusions does offer some support for 
high-dose crossmatch compatible granulocyte transfusions. The Council of Europe 
does not currently include prophylaxis as an indication for granulocyte transfusions. 
Adverse Reactions
As with other blood components, adverse reactions may occur, with febrile non-
haemolytic transfusion reactions (FNHTR) being the most common and often dose 
related. The development of HLA antibodies and subsequent immune refractoriness 
to platelet components may further complicate blood transfusion support in recipients 
of granulocytes.
4.11  Plasma Components
ABO Compatibility
To avoid red cell haemolysis caused by transfusion of donor anti-A or anti-B, the 
ABO group of plasma components should be compatible with the ABO group of 
the recipient. 
If high titre anti-A or anti-B are present in the plasma, the unit will be labelled accordingly 
and should only be transfused to a recipient with a compatible ABO group. 
Table 4.14: ABO Compatibility of Fresh Frozen Plasma and Cryoprecipitate#
Patient’s ABO Blood Group
ABO Group of Plasma Component
ABO Unknown
AB if urgent
O
O§ or A or B or AB
A
A or AB
B
B or AB
AB
AB (A if AB is unavailable)
#  Cryoprecipitate is free from high titre isoagglutinins anti-A and anti-B and can usually be given regardless 
of ABO group, however it is usual to follow the compatibility rules.
§ Group O fresh frozen plasma is no longer routinely available.
Page 52 
Transfusion Medicine Handbook 3rd Edition

RhD Compatibility
Although frozen plasma components may contain small amounts of red cell stroma, 
sensitisation following transfusion of RhD positive units is most unlikely, as stroma 
is less immunogenic than intact red cells. Therefore, FFP and cryoprecipitate of any 
RhD type may be given, regardless of the RhD type of the recipient. No prophylactic 
anti-D immunoglobulin need be given if RhD negative patients receive RhD positive 
FFP or cryoprecipitate.
Clinical Indications
Guidance on the indications for and dose of plasma components may be sought from 
a haematologist or NZBS Transfusion Medicine Specialist.
The following references provide recommendations for the appropriate use of plasma 
components:
■  
Australian NBA Patient Blood Management Guidelines
■  
2013 ASTH Consensus Guidelines for Warfarin Reversal
■  
2004 BCSH Guidelines for the Use of Fresh-Frozen Plasma, Cryoprecipitate 
and Cryosupernatant

Adverse Reactions
Acute transfusion reactions to plasma components may be seen and include febrile 
non-haemolytic transfusion reactions (FNHTR), allergic reactions to plasma protein 
antigens, circulatory overload (TACO) following transfusion of volumes excessive for the 
patient, haemolytic reactions due to ABO incompatible plasma, bacterial contamination 
and transfusion-related acute lung injury (TRALI), although the latter has reduced in 
frequency following the introduction of male-only plasma (see Chapter 7: Adverse 
Effects of Transfusion
). 
Contraindications  
It is not appropriate to use plasma components as a plasma expander or for 
replacement of plasma proteins in chronic hypoproteinaemic states. Fresh frozen 
plasma is generally not used for plasma exchange procedures except where performed 
for thrombotic thrombocytopenic purpura or in the presence of severe coagulopathy. 
The use of fresh frozen plasma is generally not considered appropriate for treating 
immunodeficiency states or for urgent reversal of vitamin K deficiency due to warfarin 
anticoagulation when a prothrombin complex concentrate (PCC) is readily available.
4.12  Fresh Frozen Plasma
Fresh frozen plasma is collected using an apheresis procedure and rapidly frozen 
within 8 hours of collection to maintain labile coagulation factors. 
Transfusion Medicine Handbook 3rd Edition 
Page 53

Table 4.15: Clinical Indications for Use of FFP
Indication
Comments
Single Coagulation 
■  
  When a specific factor concentrate is unavailable or is 
Factor/Protein 
inappropriate, including isolated deficiency of factor II, 
Deficiencies
V, VII, X, XI, XIII, antithrombin, C1-esterase inhibitor or 
pseudocholinesterase.
■  
The dose will depend on the clinical circumstances 
and the required level of activity in the patient. Consult 
a haematologist or NZBS TMS/MO.
Massive Blood 
■  
 In patients with clinical y abnormal haemostasis and 
Transfusion
reduced levels of coagulation factors following rapid 
transfusion of large volumes of blood.
■  
Massive transfusion protocols (MTP) empirically provide 
FFP units in a ratio to red cells of 1:1.
■  
Where a MTP is not available, an adult dose of 12-15 
mL/kg (i.e., 1 L or 4 units FFP) is likely to be required 
after 1-1.5 x blood volume replacement in order to 
maintain the PT/APTT <1.5 x mean control.
■  
In patients with ongoing blood loss and consumption of 
coagulation factors, close monitoring of clinical status 
and levels of coagulation factors should be used to 
guide additional doses of FFP. Note however that the 
INR/APTT may not fully correct with the use of FFP.
Reversal of 
■  
Use of FFP in this setting should be based on ASTH 
Warfarin Effect
consensus guidelines (see Section 6.5.1: Warfarin). 
■  
In summary, FFP should only be used to reverse 
warfarin anticoagulation in the presence of bleeding 
or prior to emergency surgery where a prothrombin 
complex concentrate (PCC) is unavailable or deemed 
inappropriate. In the case of life threatening bleeding, 
FFP may have a supplementary role in addition to PCC 
for warfarin reversal. 
Thrombotic 
■  
Accepted treatment is plasma exchange using FFP or 
Thrombocytopenic 
cryosupernatant plasma as replacement fluid.
Purpura (TTP)
■  
If apheresis is not immediately available, infusion of FFP 
or cryosupernatant plasma may be given until plasma 
exchange can be initiated. 
Page 54 
Transfusion Medicine Handbook 3rd Edition

Table 4.15: Clinical Indications for Use of FFP continued
Indication
Comments
Liver Disease
■  
FFP may be appropriate in the presence of bleeding 
and abnormal coagulation, or as prophylaxis prior to 
invasive procedures. 
■  
Due to reduced levels of natural anticoagulant proteins 
in liver disease, values of PT/APTT may overestimate 
the bleeding risk in liver disease.
■  
The usual adult dose is 10-15 mL/kg, however the 
response in liver disease is variable, partial and transient 
and close laboratory monitoring may be required.
Cardiac Surgery
■  
There is no evidence that prophylactic use of FFP (or 
cryoprecipitate and platelets) reduces bleeding.
■  
FFP (and other components) may be used to correct 
coagulopathy in bleeding patients, guided by clinical 
response and laboratory monitoring.
Disseminated 
■  
Indicated only when the consumptive coagulopathy is 
Intravascular 
complicated by bleeding, in which case maintaining PT/
Coagulation (DIC)
APTT <1.5 x mean control and fibrinogen >1.5 g/L may 
be of benefit.
■  
The initial recommended dose is 15 mL/kg, however 
this will depend on the severity of the DIC.
■  
Subsequent doses should be guided by frequent 
laboratory testing. Cryoprecipitate may be required if 
fibrinogen is severely reduced.
4.13   Cryoprecipitate Apheresis - High Fibrinogen
Cryoprecipitate is a concentrated source of fibrinogen and also contains von Willebrand 
factor, factor VIII, factor XIII and fibronectin. 
A dose of one unit per 30 kg body weight will produce an increment in plasma fibrinogen 
of approximately 1.0 g/L. 
Table 4.16: Clinical Indications for Use of Cryoprecipitate
Indication
Comments
Disseminated 
■  
Consumptive fibrinogen deficiency is commonly 
Intravascular 
encountered in DIC.
Coagulation (DIC) with 
Bleeding

■  
At fibrinogen levels lower than 1.5 g/L and where 
there is clinical bleeding, use of cryoprecipitate to 
maintain the fibrinogen level above 1.5 g/L may be 
indicated.
Transfusion Medicine Handbook 3rd Edition 
Page 55

Table 4.16: Clinical Indications for Use of Cryoprecipitate continued
Indication
Comments
Fibrinogen Deficiency 
■  
Cryoprecipitate may be appropriate where there 
and Dysfibrinogenaemia 
is clinical bleeding in the event of an invasive 
procedure, trauma or DIC.
■  
The actual dose should be determined from the 
recipient’s measured functional fibrinogen level, the 
nature and degree of bleeding and other relevant 
clinical factors.
Coagulation Factor 
■  
May be used as an alternative product for the 
Deficiencies 
treatment of bleeding associated with von 
Willebrand disease, haemophilia A and deficiency 
of factor XIII (fibrin stabilising factor) if specific 
concentrates are not available or are considered 
inappropriate.
■  
The dose will depend on factor levels and the 
nature and extent of bleeding.
Bleeding Associated 
■  
The transfusion of one unit per 30 kg body weight 
with Uraemia
usually is effective in controlling bleeding however 
repeated doses may be necessary.
4.14   Cryosupernatant Plasma
Cryosupernatant plasma is the supernatant from apheresis cryoprecipitate frozen within 
2 hours of collection and is essentially FFP that has been depleted of factor VIII, von 
Willebrand factor (high molecular weight multimers being more thoroughly removed 
than smaller multimers), factor XIII, fibrinogen and fibronectin.
Cryosupernatant may be used as an alternative to FFP as a source of ADAMTS-13 
protease (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, 
member 13) without replacing high molecular weight multimer vWF during plasma 
exchange in the treatment of thrombotic thrombocytopenic purpura.
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5
FRACTIONATED PRODUCTS
Fractionated products, also known as plasma derivatives, are partial y purified 
therapeutic preparations of human plasma proteins. They are manufactured under 
pharmaceutical conditions from large volumes of donor plasma with the final products 
supplied as freeze dried powders or solutions.
Careful screening of every donation contributing to a plasma pool is vital since any 
one donation could potentially introduce infectious agents into the pool. Even with 
rigorous screening of every donor and infectious diseases testing of every donation, 
some infectious agents might still find their way into the plasma pool. To counter this 
risk, manufacturing processes include two or more specific steps to inactivate any 
such agents that may escape detection.
Some points to note regarding transfusion of fractionated products:
■  
The manufacturer’s instructions should be carefully read. Specific information 
about the administration of each product is given in the product information 
sheet, which comes packaged with each unit.
■  
Products should be transfused promptly following issue from the blood bank. If 
there is any delay they must be stored in a refrigerator at 2-8°C (unless otherwise 
indicated by the manufacturer). 
■  
Freeze-dried preparations must be infused immediately after reconstitution. Do 
not refrigerate after reconstitution.
■  
Products not containing an antimicrobial preservative must be transfused within 
3-4 hours of breaking the product seal. 
■  
Multiple vials or bottles of the same product may be pooled together immediately 
prior to infusion to the patient.
■  
Products should not be used if turbidity or particulate matter is present in the 
vial or bottle. If observed this should be reported to NZBS.
■  
ABO compatibility does not normally need to be considered. Residual anti-A and 
anti-B in the final product are usually at clinically insignificant levels. However 
in some situations, such as where high doses of Intragam® P are being given 
to non-group O patients, these patients should be monitored for signs of 
intravascular haemolysis.
■  
Patients may experience adverse reactions due to transfusion of fractionated 
products. These should be reported to NZBS using a Notification of Adverse 
Reaction to Fractionated Blood Product
 form.
The information contained within this chapter relates to the fractionated products 
distributed by NZBS and has been adapted from the most recently available datasheet 
and/or the manufacturer’s product information sheet for each product. These sources 
should be consulted prior to administration. Current versions of the datasheets 
can be accessed through the Clinical Information section of the NZBS website 
(www.nzblood.co.nz) and also the Medsafe website (www.medsafe.govt.nz). NZBS 
Transfusion Medicine Specialists/Medical Officers and Transfusion Nurse Specialists 
can also provide valuable information regarding the use of fractionated products. 
Transfusion Medicine Handbook 3rd Edition 
Page 57

5.1 
Coagulation Factors
The National Haemophilia Management Group has produced guidelines for the 
management of haemophilia, including vWD, and these are available from the 
Haemophilia Centres. Most patients diagnosed with haemophilia A and B have their 
treatment supervised by a specialist haematologist. For any individual patient, the 
various fractionated and recombinant products used in the management of haemophilia 
are not interchangeable without prior discussion with the treating haematologist.
The following guidelines are to assist in the immediate management of a patient until 
consultation with a specialist haematologist or NZBS Transfusion Medicine Specialist. 
The exact loading and maintenance dose and dosing interval should be based on the 
patient’s clinical condition and response to therapy. Where possible, pre- and post-
infusion factor assays should be carried out, at least for the first course of treatment. 
Coagulation factor therapy as a continuous infusion to cover surgical procedures should 
be administered under the supervision of a specialist haematologist and with laboratory 
tests performed to ensure that the desired plasma factor concentrations are achieved. 
5.1.1 Biostate® (Factor VIII)
Biostate® is a high purity, sterile, freeze-dried powder containing purified human 
coagulation factor VIII (FVIII) and human von Willebrand factor (vWF) complex. Biostate® 
is available as vials of 500 IU and 1,000 IU factor VIII. The reconstituted product has a 
vWF to FVIII ratio of 2:1 as detailed in Table 5.1. Biostate® contains 10 mg/mL human 
albumin as a stabiliser.
The FVIII/vWF complex in Biostate® is purified from cryoprecipitate using selective 
precipitation and chromatography steps. The manufacturing process of Biostate® 
includes solvent detergent and dry heat treatment steps to reduce the potential for 
viral transmission. The combination of solvent detergent, dry heat treatment, and 
partitioning steps are effective for inactivation/removal of HIV, hepatitis A, hepatitis B, 
and hepatitis C and also have some effect on parvovirus B19.
Table 5.1: Biostate® Composition
Active ingredients 
Biostate®
IU/vial (nominal)
500 IU (50 IU/mL)
1000 IU (100 IU/mL)
Factor VIII
500
1000
vWF:RCo1
1000
2000
Reconstitution 
10
10
volume (mL)
1vWF:Ristocetin Cofactor – an in vitro indicator of vWF activity.
Indications for Use
Biostate® is indicated for:
■  
Treatment and prophylaxis of bleeding associated with FVIII deficiency due to 
haemophilia A
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Transfusion Medicine Handbook 3rd Edition

■  
Treatment and prophylaxis of bleeding associated with von Willebrand 
disease (vWD) when desmopressin (DDAVP) treatment alone is ineffective or 
contraindicated
The number of vials of Biostate® to be reconstituted for administration is determined by 
dividing the total number of International Units (IU) required by 500 or 1,000 (according 
to vial size being used), rounded up to the nearest whole number of vials. 
Table 5.2: Biostate® Dosage Guidelines for Haemophilia A
Indication
Dose  
Dose 
Treatment 
Target FVIII 
(IU/kg)
Frequency 
Duration 
(%) (IU/dL)
(per day)
(days)
Minor haemorrhage 
10-15
1-2
1-2
peak 20-30
Moderate to severe 
haemorrhage

■  Haemarthroses
15-40
1-3
1-4
peak 30-80
Life threatening 
haemorrhage

■   Intracranial 
50-60
2-3
7-10
peak ≥100 
haemorrhage
trough 80-100
Minor surgery 
■  Loading dose
20-30
stat
preoperatively
peak 40-60
■  Maintenance1
15-30
1-2
≥4
trough 20-50
Major surgery 
■  Loading dose
40-50
stat
preoperatively
peak 80-100
■  Maintenance1
10-25
1-3
≥7
trough 40-80
Dentistry2
■  Loading dose
35-40
stat
preoperatively
peak 70-80
■  Maintenance1
25-30
2
1-3
trough 50-60
Prophylaxis
25-40
3x/week
ongoing
trough 1
1An alternative is to use continuous infusion.
2 For single tooth extraction, extensive dental clearance or surgery, higher levels may be necessary for 

longer periods of at least 6 - 10 days. The use of an antifibrinolytic agent such as tranexamic acid is 
strongly recommended.

Transfusion Medicine Handbook 3rd Edition 
Page 59

Table 5.3: Biostate® Dosage Guidelines for Von Willebrand Disease1
Indication
Dose (IU/kg)
Dose 
Treatment  Target FVIII/
Frequency   Duration  
vWF (%)  
(per day)
(days)
(IU/dL)
FVIII:C vWF:RCo
Spontaneous  12.5-25
25-50
initial
-
peak vWF >50, 
haemorrhage
FVIII >30
12.5
25
1-2
2-4
trough vWF >30
Minor surgery2 
30
60
1
2-4
trough  
vWF/FVIII >30
Major surgery2  30-40
60-80
preoperatively
-
peak vWF >100, 
FVIII >60
15-30
30-60
1-2
5-10
trough  
vWF/FVIII >50
Prophylaxis
12.5-25
25-40
3x/week
ongoing
trough 1
1 Dosage guidelines above are for patients with severely reduced vWF levels, e.g. <10% of normal. Doses 
may need to be adjusted down in patients with less severe vWF deficiencies (>20% of normal) to ensure 
that the desired plasma concentrations of vWF and FVIII are achieved. It is recommended that plasma 
vWF and FVIII concentrations are determined at suitable time intervals.

2An alternative is to use continuous infusion.
Precautions
■  
Allergic reactions 
 
Allergic reactions or fever are rarely observed. Depending on the nature of an 
adverse reaction, the rate of injection should be slowed or stopped to alleviate 
symptoms.
■  
Antibodies to factor VIII   
Patients with congenital factor VIII deficiency may develop neutralising 
alloantibodies (inhibitors) to factor VIII after treatment. If this occurs specialist 
advice must be sought.
■  
Antibodies to von Willebrand factor 
 
Patients with von Willebrand disease, especially type 3 patients, may very 
rarely develop neutralising alloantibodies (inhibitors) to von Willebrand factor. 
Such antibodies may occur in close association with anaphylactic reactions. 
Therefore patients experiencing anaphylactic reactions should be evaluated for 
the presence of an inhibitor.
■  
Thrombosis   
Thromboembolic events have rarely been reported in vWD patients receiving 
coagulation factor replacement therapy, especially in the setting of known risk 
factors for thrombosis, and may be related to the generation of supranormal 
FVIII levels.
5.1.2 MonoFIX®-VF (Factor IX)
MonoFIX®-VF is a sterile, freeze-dried powder containing purified human coagulation 
factor IX. MonoFIX®-VF is available as vials of 500 IU and 1,000 IU factor IX. Each vial 
also contains small amounts of heparin, antithrombin III and plasma proteins. 
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Transfusion Medicine Handbook 3rd Edition

The factor IX in MonoFIX®-VF is purified using ion-exchange and heparin affinity 
chromatography to remove other vitamin K-dependent factors II, VII and X. The 
manufacturing process of MonoFIX®-VF includes solvent detergent treatment and 
nanofiltration steps to reduce the potential for viral transmission. The current procedures 
are effective for inactivation/removal of HIV, hepatitis A, hepatitis B, and hepatitis C 
and also have some effect on parvovirus B19.
Indications for Use 
MonoFIX®-VF is indicated for: 
■  
Treatment and prophylaxis of bleeding associated with factor IX deficiency due 
to haemophilia B (Christmas disease)
MonoFIX®-VF is not indicated for the treatment of factor II, VII or X deficiency because 
it does not contain therapeutic levels of these coagulation factors. MonoFIX®-VF is 
not indicated for the treatment of haemophilia A patients with factor VIII inhibitors.
The number of vials of MonoFIX®-VF to be reconstituted for administration is determined 
by dividing the total number of International Units (IU) required by 500 or 1,000 
(according to vial size being used), rounded up to the nearest whole number of vials. 
Table 5.4: MonoFIX®-VF Dosing Guideline for Haemophilia B
Indication
Dose  
Dose 
Treatment 
Target FVIII 
(IU/kg)
Frequency 
Duration 
(%) (IU/dL)
(per day)
(days)
Prophylaxis1 
25-40
2x/week
ongoing
trough 1
Minor haemorrhage
20-30
1
1-2
peak 20-30
Moderate to severe 
haemorrhage

■  Haemarthroses
30-50
1-2
1-5
peak 30-50
Life threatening 
haemorrhage

■   Intracranial 
peak ≥100 
haemorrhage
80-100
2
10-12
trough 80-100
Minor surgery2 
■  Loading dose
40-60
stat
preoperatively
peak 40-60
■  Maintenance3, 4
15-40
1-2
7-10
trough 20-50
Major surgery 
■  Loading dose
70-100
stat
preoperatively
peak 70-100
■  Maintenance3, 4
20-90
1-2
10-12
trough 20-90
1Prophylaxis in children.
2 Includes single tooth extraction. The use of an antifibrinolytic agent such as tranexamic acid is strongly 

recommended. 
3 Initially (days 1-3) aim for levels at the higher end of this range. Gradually reduce to lower level during 
subsequent days.
4An alternative is to use continuous infusion.
Transfusion Medicine Handbook 3rd Edition 
Page 61

Precautions
■  
Allergic reactions 
 
Allergic reactions or fever are rarely observed. Depending on the nature of an 
adverse reaction, the rate of injection should be slowed or stopped to alleviate 
symptoms.
■  
Antibodies to factor IX   
Patients with congenital factor IX deficiency may develop neutralising 
alloantibodies (inhibitors) to factor IX after treatment. If this occurs specialist 
advice must be sought. The reported prevalence for the formation of inhibitors in 
patients receiving plasma-derived factor IX is approximately 4%. There has been 
no clinical experience with MonoFIX®-VF with respect to inhibitor development 
in previously untreated patients.
■  
Heparin 
 
MonoFIX®-VF contains 50 - 140 IU heparin in each 500 IU vial and 100 - 280 IU 
heparin in each 1000 IU vial. Heparin is known to cause thrombocytopenia and 
the possibility of heparin-induced thrombocytopenia (HIT) syndrome should be 
considered if thrombocytopenia, with or without thrombosis, develops during 
treatment. Consideration should be given to the clinical effect of heparin if high 
doses of MonoFIX®-VF are required.
■  
Laboratory tests 
 
MonoFIX®-VF is formulated with heparin and antithrombin. Therefore the results 
of anticoagulation tests should be interpreted with care.
■  
Thrombosis and DIC  
 
High doses of prothrombin complex concentrates (PCC) have been associated 
with disseminated intravascular coagulation (DIC). Although MonoFIX®-VF 
contains purified factor IX, the potential risk of thrombosis and DIC should be 
recognised. The use of products containing factor IX could be hazardous in 
patients with a history of fibrinolysis, myocardial infarction, DIC or liver disease.
5.1.3 Prothrombinex®-VF (Factors II, IX and X)
Prothrombinex®-VF is a sterile, freeze-dried powder containing purified human 
coagulation factors II, IX, and X. When reconstituted each vial contains 500 IU of 
factors IX, approximately 500 IU of factors II and X, and 25 IU antithrombin III, 200 IU 
heparin. The product also contains small amounts of factors V and VII. 
Prothrombinex®-VF is prepared by adsorption of coagulation factors from plasma onto 
an ion-exchange medium followed by selective elution. The manufacturing process 
of Prothrombinex®-VF contains dedicated steps including dry heat treatment and 
nanofiltration to reduce the potential for viral transmission. The current procedures 
are effective for inactivation/removal of HIV, hepatitis A, hepatitis B, and hepatitis C 
and may also have some effect on parvovirus B19.
The coagulation factors II, VII, IX and X, synthesised in the liver with the help of vitamin 
K, are together commonly called the prothrombin complex. 
Isolated congenital deficiency of factor IX is known as haemophilia B. Isolated deficiency 
of factor II or factor X is very rare but in severe form can cause a bleeding tendency 
similar to that seen in classical haemophilia. Isolated severe deficiency of factor VII 
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Transfusion Medicine Handbook 3rd Edition

leads to reduced thrombin formation and a bleeding tendency due to impaired fibrin 
formation and impaired primary haemostasis. 
Acquired deficiency of the vitamin K-dependent coagulation factors occurs during 
treatment with coumarin vitamin K antagonists such as warfarin. It may also result from 
vitamin K deficiency due to malabsorption syndromes, antibiotic therapy, cholestasis 
or prolonged parenteral alimentation. If the deficiency progresses, a severe bleeding 
tendency results, characterised typically by retroperitoneal or cerebral bleeds rather 
than muscle and joint haemorrhage. 
Severe hepatic insufficiency also results in markedly reduced levels of the vitamin 
K-dependent coagulation factors and may lead to a clinical bleeding tendency. The 
haemostatic situation is however often complex due to simultaneous ongoing low-
grade intravascular coagulation, low platelet levels, deficiency of coagulation inhibitors 
and disturbed fibrinolysis.
Indications for Use 
Prothrombinex®-VF is indicated for: 
■  
Treatment and perioperative prophylaxis of bleeding associated with acquired 
deficiency of prothrombin complex factors such as that caused by treatment 
with vitamin K antagonists, or in case of overdose of vitamin K antagonists, 
when rapid correction of the deficiency is required 
■  
Treatment and prophylaxis of bleeding associated with single (or multiple) 
congenital deficiency of factors IX, II or X when purified specific coagulation 
factor product is not available 
Section 6.4: Oral Anticoagulant – Warfarin Induced Bleeding or Overdose of this 
Handbook summarises the updated Australasian Society of Thrombosis and 
Haemostasis (ASTH) Consensus Guidelines for Warfarin Reversal published in the 
Medical Journal of Australia, 198 (4): 198-199, 2013. The recommendations for the use 
of prothrombin complex concentrate (PCC) in the setting of warfarin-related bleeding 
or warfarin overdose have been incorporated in the NZBS app Reversing Warfarin
available for iPhone and Android. Consultation with a specialist haematologist or NZBS 
Transfusion Medicine Specialist/Medical Officer is recommended.
Table 5.5: Prothrombinex®-VF Dosing Guideline for Haemophilia B
Indication
Dose  
Dose 
Treatment 
Target FIX 
(IU/kg)
Frequency 
Duration 
(%) (IU/dL)
(per day)
(days)
Minor haemorrhage
20-30
1
1-2
peak 20-30
Moderate to severe 
haemorrhage

■  Haemarthroses
30-50
1-2
1-5
peak 30-50
Minor surgery 
■  Loading dose
40-60
stat
preoperatively
peak 40-60
■  Maintenance
15-40
1-2
7-10
trough 20-50
Transfusion Medicine Handbook 3rd Edition 
Page 63

For congenital deficiencies of factors II and X, calculation of the required dose of 
Prothrombinex®-VF is based on recovery data obtained for other PCC products 
showing that 1 U of factor II or X per kg body weight raises the respective plasma 
factor activity by 2% of normal. 
Required units (IU) = body weight (kg) x desired rise in factor II or X (as %) x 0.5
Prothrombinex®-VF should not be infused at a rate greater than 3 mL/minute.
Precautions
■  
Allergic reactions 
 
Allergic reactions are rarely observed although severe anaphylaxis has been 
reported, particularly in patients with factor IX inhibitors. Depending on the 
nature of an adverse reaction, the rate of injection should be slowed or stopped 
to alleviate symptoms.
■  
Antibodies to factor IX   
Patients with congenital factor IX deficiency may develop neutralising 
alloantibodies (inhibitors) to factor IX after treatment. The reported prevalence 
for the formation of inhibitors in patients receiving plasma-derived factor IX is 
approximately 4%. 
■  
Antifibrinolytic agents   
Use of Prothrombinex®-VF with epsilonaminocaproic acid or tranexamic acid 
is not recommended since only limited data are available on the concomitant 
administration of prothrombin complex concentrates and antifibrinolytic agents.
■  
Heparin 
 
Prothrombinex®-VF contains 200 IU heparin in each vial. Heparin is 
known to cause thrombocytopenia and the possibility of heparin-induced 
thrombocytopenia (HIT) syndrome should be considered if thrombocytopenia, 
with or without thrombosis, develops during treatment. Consideration should 
be given to the clinical effect of heparin if high doses of Prothrombinex®-VF 
are required.
■  
Thrombosis and DIC 
 
Patients receiving Prothrombinex®-VF, especially at doses greater than 50 IU/
kg of factor IX or following repeated doses, may be predisposed to venous and 
arterial thromboembolism, DIC or myocardial infarction. It should be used with 
caution in neonates, in who immature hepatic function may lead to delayed 
clearance of activated coagulation factors and an increased risk of thrombotic 
complications. 
5.1.4  FEIBA NF® (Factor VIII inhibitor bypassing fraction)
FEIBA NF® is a sterile, freeze-dried powder of human plasma fraction with factor VIII 
inhibitor bypassing activity. FEIBA NF® is available as 20 mL vials containing 500 U 
and 1000 U factor VIII inhibitor bypassing activity for reconstitution and intravenous 
administration. The potency of FEIBA NF® is expressed in arbitrary units. One Unit 
of activity is defined as that amount of FEIBA NF® that shortens the activated partial 
thromboplastin time (APTT) of a high titre factor VIII inhibitor reference plasma to 50% 
of the blank value.
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Transfusion Medicine Handbook 3rd Edition

FEIBA NF® is prepared by adsorption of coagulation factors from plasma onto an 
ion-exchange medium followed by selective elution. The manufacturing process of 
FEIBA NF® contains dedicated steps including nanofiltration and vapour heat treatment 
to reduce the potential for viral transmission. The current procedures are effective for 
inactivation/removal of HIV, hepatitis B, and hepatitis C and may also have some effect 
on hepatitis A and parvovirus B19.
FEIBA NF® is a concentrate of vitamin K-dependent factors in both zymogen and active 
form (factors II, IX, and X, mainly non-activated, and factor VII, mainly activated). The 
product contains approximately equal unitages of factor VIII inhibitor bypassing activity 
and prothrombin complex factors. In addition, 1 - 6 units of factor VIII coagulant antigen 
(FVIII C:Ag) per mL are present. The preparation contains only traces of factors of the 
kinin generating system. It contains no heparin.
The process of coagulation involves activation of factor X to form Xa, which with 
cofactor Va catalyses the formation of thrombin from prothrombin. The production of 
sufficient quantities of Xa usually requires a complex of factors VIIIa and IXa. Patients 
(often those with haemophilia A or B) can acquire inhibitors to factor VIII or IX during the 
treatment with factor VIII or IX replacement therapy, which then prevents the formation 
of the complex that catalyses Xa production. FEIBA NF® results in the generation of 
Xa and thrombin without the help of the factor VIIIa-IXa complex, thereby bypassing 
the inhibitory action of factor VIII (or factor IX) inhibitors.
Indications for Use
FEIBA NF® is indicated for: 
■  
Routine prophylaxis of bleeding episodes in haemophilia A and B patients 
with inhibitors, experiencing ≥ 12 bleeding episodes per year and refractory to 
increased dosing with, respectively, factor VIII and IX concentrates
■  
Treatment of bleeding episodes and to cover surgical interventions in haemophilia 
A and B patients with, respectively, factor VIII and IX inhibitors
■  
Longterm use, in combination with factor VIII concentrates, for immune tolerance 
induction to eliminate factor VIII inhibitors in patients with haemophilia A, so as 
to allow for regular treatment with factor VIII concentrates as in patients without 
inhibitors
■  
Treatment of severe or life-threatening bleeding episodes in non-haemophiliacs 
with acquired inhibitors to factors VIII, XI and XII
Clinical experience suggests that patients with a factor VIII inhibitor titre < 5 Bethesda 
units (BU) may be successfully treated with antihemophilic factor (AHF). Patients with 
titres ranging between 5 BU and 10 BU may either be treated with AHF or FEIBA 
NF®. Patients with factor VIII inhibitor titres > 10 BU have generally been refractory to 
treatment with AHF. However, since a single dose of FEIBA NF® contains considerably 
less factor VIII than factor VIII concentrate, FEIBA NF® is considered the treatment of 
choice in high responder patients, even if the current inhibitor titre is low.
Transfusion Medicine Handbook 3rd Edition 
Page 65

Table 5.6:  Guideline for Treatment of Patients with Haemophilia A and Factor VIII 
Inhibitors
Inhibitor Titre 
Response to 
Minor / 
Severe / Life-
(BU1/mL)
FVIII 
Moderate 
threatening Bleeding 
Bleeding
or Surgery
< 5
low responder
FVIII or FEIBA NF®
FVIII or FEIBA NF®
> 5
high responder
FEIBA NF®
FEIBA NF®
5 - 10
low responder
FVIII or FEIBA NF®
FEIBA NF®
5 - 10
high responder
FEIBA NF®
FEIBA NF®
< 10
low responder
FEIBA NF®
FEIBA NF®
> 10
high responder
FEIBA NF®
FEIBA NF®
1 Bethesda Unit is defined as that amount of antibody that will inhibit 50% of the factor VIII activity of fresh 
plasma after incubation for 2 hours at 37 °C.
Dosage and Administration
Dosage is independent of the patient’s inhibitor titre. As a general rule, a dose of 50 
- 100 U FEIBA NF® per kilogram body weight is recommended. However, due to the 
risk of thrombosis, the total daily dose should not exceed 200 U/kg and, for any one 
dose, the infusion rate should not exceed 2 U/kg per minute. Due to varying response 
to treatment the following dosage recommendations are only guidelines. 
Table 5.7: FEIBA NF® Dosing Guideline
Bleeding 
Dose1  
Dose Frequency  Treatment Duration  
Indication
(U/kg)
(day)
Prophylaxis2
70-100
alternate day
ongoing
Surgery
50-100
4
preoperatively and until 
wound healing
Mucous membrane3 
50
4
until clinical improvement
Joint, muscle, soft 
50-75
2
until clinical improvement
tissue - mild to 
moderate
Joint, muscle, soft 
100
2
until clinical improvement
tissue - severe
Other severe4  
100
2
until clinical improvement
e.g., CNS
1Single doses of 100 U/kg and daily doses of 200 U/kg body weight should not be exceeded.
2Dose recommendations, based on body weight, are the same for paediatric patients as for adults.
3 If bleeding is not controlled the dose may be increased to 100 U/kg, provided the maximum daily dose 

is not exceeded.
4 In individual cases the frequency may be increased to 6-hourly until clinical improvement, provided the 
maximum daily dose is not exceeded.
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Contraindications
FEIBA NF® is contraindicated in cardiac surgery involving cardiopulmonary bypass 
and procedures involving extracorporeal membrane oxygenation (ECMO) due to the 
high risk of thrombotic adverse events.
Precautions
■  
Allergic reactions 
 
FEIBA NF® has been associated with severe allergic and anaphylactoid reactions.
■  
Anamnestic response   
Administration of FEIBA NF® to patients with inhibitors may result in an initial 
anamnestic rise in inhibitor levels. Clinical data suggest that the efficacy of FEIBA 
NF® is not reduced. Inhibitor levels may decrease over time with continued 
administration of FEIBA NF®.
■  
Laboratory tests 
 
In vitro tests such as APTT, whole blood clotting time (WBCT) and 
thromboelastography (TEG) used to monitor efficacy may not correlate with 
clinical improvement. Attempts to normalise these values by increasing the 
dose of FEIBA NF® are discouraged and may induce DIC through overdosage.
■  
Passive anti-HBs transfer 
 
Administration of FEIBA NF® with a transitory rise of passively transferred 
hepatitis B surface antibodies may mislead the interpretation of positive serology 
test results. 
■  
Sodium 
 
The maximum daily dose of FEIBA NF® may contain > 200 mg sodium and this 
should be taken into consideration for patients on a sodium-restricted diet and/
or with renal impairment.
■  
Thrombosis   
Patients should not receive single doses of FEIBA NF® > 100 U/kg body weight 
or daily doses > 200 U/kg body weight as these may predispose venous and 
arterial thromboembolism, DIC, myocardial infarction or stroke. Patients receiving 
doses such as these should be monitored for the development of adverse events. 
The possible presence of risk factors for thromboembolism, even in patients 
with haemophilia, should always be considered.
Interactions with Other Medicines
The use of tranexamic acid, an antifibrinolytic agent, in combination with FEIBA NF® is 
not recommended due to an increased risk of thrombotic events. If treatment with both 
is indicated the products should be administered at least 12 hours apart. Concomitant 
use with recombinant factor VIIa may potentially result in an adverse thrombotic event.
5.1.5 RiaSTAP® (Fibrinogen) 
RiaSTAP® does not have full New Zealand registration and is in limited supply so 
consultation with an NZBS Transfusion Medicine Specialist/Medical Officer is required 
prior to release of this product.
RiaSTAP® is a freeze-dried powder of purified human fibrinogen (factor I). Each 50 mL 
vial when reconstituted contains 1 g of human fibrinogen for intravenous administration.
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Indications for Use 
RiaSTAP® is indicated for: 
■  
Prophylaxis and treatment of bleeding in patients with congenital fibrinogen 
deficiency including afibrinogenaemia and hypofibrinogenaemia
Dosage and Administration
The (functional) fibrinogen level should be determined in order to calculate individual 
dosage requirements. The frequency of administration should be determined on an 
individual patient basis by regular measurement of plasma fibrinogen and continuous 
monitoring of the clinical condition of the patient. Dosage recommendations in the 
treatment of children are the same as for adults.
Dose of RiaSTAP® (mg/kg body weight) = target level (g/L) – measured level (g/L)
  
0.017 (g/L per mg/kg body weight)
If the serum fibrinogen level is not known the recommended dose is 70 mg per kilogram 
body weight administered intravenously.
As a guide for subsequent dosing the target level of 1 g/L for minor events should 
be maintained for three days. The target level of 1.5 g/L for major events should be 
maintained for seven days.
Precautions
■  
Thrombosis   
There is a risk of thrombosis when patients with congenital fibrinogen deficiency 
are treated with human fibrinogen, particularly with high or repeat doses. 
Patients, particularly those with risk factors for thromboembolic disease including 
neonates, should be monitored closely for signs and symptoms of thrombosis.
■  
Serum sodium  
 
RiaSTAP® contains up to 164 mg (7.1 mmol) sodium per vial and this should 
be taken into consideration for patients on a sodium-restricted diet and/or with 
renal impairment.
Adverse Events
The following adverse reactions have been reported from clinical studies.
Table 5.8: Adverse Events Associated with Administration of RiaSTAP® 
Event
Frequency
Urticaria, rash, fall in blood pressure, dyspnoea
≥ 1/10,000 and < 1/1,000
Increase in body temperature
≥ 1/10,000 and < 2/1,000
Headache
≥ 1/10,000 and < 1/1,000
Thromboembolic episodes
< 1/10,000
5.1.6 Fibrogammin® P (Factor XIII)
Fibrogammin® P does not have full New Zealand registration and so consultation with an 
NZBS Transfusion Medicine Specialist/Medical Officer is required prior to product release.
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Fibrogammin® P is a freeze-dried powder of purified human factor XIII. Each vial when 
reconstituted contains 250 units of factor XIII. 
Indications for Use 
Fibrogammin® P is indicated for:
■  
The prophylaxis and treatment of bleeding associated with congenital FXIII 
deficiency
■  
Supportive therapy in the case of disturbance in wound healing associated with 
congenital FXIII deficiency, especially with venous ulcers or following extensive 
surgery
■  
The treatment of bleeding associated with acquired FXIII deficiency
Dosage and Administration
The following guideline is to assist in the immediate management of a patient until 
consultation with a specialist haematologist or NZBS Transfusion Medicine Specialist/
Medical Officer. The exact loading and maintenance dose and dosing interval should be 
based on the patient’s clinical condition and response to therapy. It is recommended to 
monitor the increase in factor XIII activity. For major surgery and severe haemorrhage 
the aim is to obtain normal values.
Table 5.9: Fibrogammin® P Dosing Guideline 
Indication
Dose  
Treatment Duration 
(IU/kg)
Congenital FXIII 
deficiency

Prophylaxis
10
approx. once per month, 
individualised to bleeding frequency
Moderate to severe 
10-20
daily for severe haemorrhage and 
haemorrhage1
until bleeding stops
Surgery
■  Loading dose
35
preoperatively
■  Maintenance
10
daily until complete wound healing
Acquired FXIII 
deficiency

Moderate to severe 
15-20
daily until bleeding stops or normal 
haemorrhage
FXIII levels achieved spontaneously
Disorder of wound 
healing

Surgery2
10
preoperatively and then once daily 
for 3 days
1 Severe life threatening bleeding may initially require doses up to 50 IU/kg with an aim to achieve normal 
factor XIII levels.
2In high-risk patients the dose can be increased to 15 - 20 IU/kg.
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Precautions
■  
Allergic reactions 
 
Allergic reactions or fever are rarely observed. Depending on the nature of an 
adverse reaction, the rate of injection should be slowed or stopped to alleviate 
symptoms.
■  
Antibodies to factor XIII   
Patients with congenital deficiency may rarely develop neutralising alloantibodies 
(inhibitors) to factor XIII after repeated treatment.
■  
Thrombosis   
In cases of fresh thrombosis, caution should be exercised due to the fibrin-
stabilising effect.
5.2 
Natural Inhibitors of Coagulation 
5.2.1 Thrombotrol®-VF (Antithrombin III)
Thrombotrol®-VF is a sterile, freeze-dried powder of purified human antithrombin 
III (ATIII). Each vial when reconstituted contains 1000 IU of ATIII for intravenous 
administration.
Indications for Use  
Thrombotrol®-VF is indicated in patients with hereditary deficiency of antithrombin 
under the following circumstances:
■  
Prophylactic administration for the prevention of thromboembolism in surgery, 
pregnancy and during childbirth
■  
Therapeutic administration in thrombosis or pulmonary embolism
The dose should be based on pretreatment and desired ATIII levels. The dose can 
be calculated using the following formula which is based on an incremental in-vivo 
recovery of ATIII of 2.2% per IU/kg bodyweight using a functional ATIII assay.
Dose (IU) = [Desired ATIII (IU) - Pretreatment ATIII level*(IU)] × Wt (kg)
 
2.2
* expressed as % normal level based on functional ATIII assay
Under conditions of acute consumption, the biological half-life of ATIII may be reduced 
from 2.8 days to only a few hours. Fol owing acute thrombosis where ATI I levels should 
be maintained ≥ 100% for 2 - 8 days, plasma ATIII levels determined several times per 
day may be used to guide replacement therapy.
ATIII replacement may also be given prophylactically to overcome heparin resistance 
and reduce the risk for circuit thrombosis in patients (particularly neonates) undergoing 
extracorporeal membrane oxygenation (ECMO) during cardiac surgery. In this 
situation acute consumption of ATIII may lead to low plasma ATIII levels and failure to 
achieve adequate anticoagulation despite increasing heparin infusion doses. ATIII is 
administered as either intermittent intravenous bolus doses, each over 10 - 20 minutes, 
or as a continuous infusion with the aim to maintain an activated clotting time (ACT) > 
400 seconds together with a target ATIII level of 60 - 100%. The doses required are 
typically larger than those used for replacement in hereditary deficiency.
5.2.2  Ceprotin (Protein C)
Ceprotin does not have full New Zealand registration and so consultation with an NZBS 
Transfusion Medicine Specialist/Medical Officer is required prior to product release.
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Ceprotin is a sterile, freeze-dried powder of purified human protein C. Each vial when 
reconstituted contains 1000 IU of protein C for intravenous administration.
Indications for Use 
Ceprotin is indicated for:
■  
Prophylaxis and treatment of venous thrombosis and purpura fulminans in 
paediatric and adult patients with severe congenital protein C deficiency
Dosage and Administration
The loading and maintenance dose and dosing interval should be based on the clinical 
condition, the severity of the protein C deficiency (i.e., pretreatment level) and desired 
protein C level. It is recommended to monitor the increase in protein C activity. These 
guidelines are recommended for neonatal, paediatric and adult patients.
Table 5.10: Ceprotin Dosing Guideline1
Indication
Initial   Subsequent  Maintenance   Target Protein C 
Dose  
Doses 
Dose 
(%) (IU/dL)
(IU/kg)
(IU/kg)
(IU/kg)
Acute episode/
100-120 
60-80 
45-60 
peak 100
Short term 
6 hourly for 
6-12 hourly
prophylaxis2
three doses
Long term 
-
-
45-60  
trough >25
prophylaxis
12 hourly
1Dosing should be adjusted according to the pharmokinetic profile for each individual.
2Ceprotin should be continued until desired anticoagulation is achieved. 

Adverse Reactions
Common reactions include rash, itch and lightheadedness. Other reported reactions 
include restlessness and hyperhydrosis.
Precautions
■  
Allergic reactions 
 
Ceprotin may contain traces of mouse protein and/or heparin, to which allergic 
reactions cannot be ruled out.
■  
Heparin 
 
Ceprotin contains trace amounts of heparin which may lead to heparin-induced 
thrombocytopenia (HIT).
■  
Sodium 
 
Ceprotin contains > 200 mg sodium and this should be taken into account for 
patients on a sodium-restricted diet and/or with renal impairment.
5.3  
Albumin Solutions
5.3.1   Albumex® 4 (Human albumin 4%)
Albumex® 4 contains 40 g/L albumin in solution for intravenous injection and is iso-
oncotic with human serum. It is available in vials of 50 mL and 500 mL volume. When 
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infused into adequately hydrated patients its effect is to expand the circulating blood 
volume by an amount approximately equal to the volume of Albumex® 4 infused. It is 
prepared by a combination of Cohn cold-ethanol fractionation and chromatography. 
The manufacturing process of Albumex® 4 includes pasteurisation and cold 
temperature incubation to reduce the potential for viral transmission. The current 
procedures are effective for inactivation/removal of HIV, hepatitis A, hepatitis B, and 
hepatitis C and may also be of limited value against parvovirus B19.
Indications for Use
Table 5.11: Clinical Indications for Use of Albumex® 4
Indication
Comments
Hypovolaemia / Shock 
■ 
 Preservation of an adequate circulating blood volume 
should be the primary aim of therapy. Albumex® 4 
may be the initial plasma expander of choice for 
shock associated with significant hypoalbuminaemia 
(plasma albumin < 25 g/L). 
■ 
 May also be useful following initial resuscitation with 
crystalloid or synthetic colloid solutions in patients in 
whom extended support of the intravascular volume 
is required such as seriously ill patients with multiple 
organ failure or the systemic capillary leak syndrome.
■ 
 The use of albumin for fluid resuscitation of patients 
with traumatic brain injury is not recommended.
Cardiopulmonary 
■ 
 Priming the pump for cardiopulmonary bypass 
Bypass 
 
surgery for patients with poor left ventricular function 
and other complicating factors such as long bypass 
time, anaemia or repeat surgery.
Plasma Exchange  
 
■ 
 Indicated as a replacement solution in plasma 
exchange procedures, particularly when the volume 
exchanged exceeds 20 mL/kg body weight.
■ 
 In patients with thrombotic thrombocytopenic 
purpura, fresh frozen plasma or cryosupernatant may 
be the preferred replacement solution.
Precautions
■  
Adverse effects 
 
Adverse reactions to albumin solutions are uncommon and are usually mild and 
transient. Chills, fever, urticaria, flushing, nausea, headache and dyspnoea may 
occur. More serious allergic events including hypotension and anaphylaxis are 
reported. In addition, hypotension has been reported in patients given albumin 
who are on angiotensin-converting enzyme (ACE) inhibitors.
■  
Aluminium accumulation 
 
Albumex® 4 contains trace amounts of aluminium (200 µg/L). Accumulation 
of aluminium in patients with chronic renal insufficiency has led to toxic 
manifestations such as hypercalcaemia, vitamin D-refractory osteodystrophy, 
anaemia and severe progressive encephalopathy. Therefore, when large 
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volumes of albumin are contemplated for administration to such patients, 
serious consideration should be given to these potential risks relative to the 
anticipated benefits.
■  
Circulatory overload 
 
Circulatory overload can be avoided by monitoring the rate and volume of 
infusion. Patients with cardiac failure, renal insufficiency, stabilised chronic 
anaemia or on cardiopulmonary bypass are at special risk of developing 
circulatory overload.
■  
Compatibility with other fluids 
 
Albumex® 4 should not be mixed with protein hydrolysates, amino acid solutions, 
solutions containing alcohol, or solutions containing drugs that bind to albumin 
such as calcium channel blockers.
■  
Shock    
Administration of albumin can aggravate myocardial depression when present 
in patients with shock.
Safety of Albumin for Fluid Resuscitation
In 2011 the Cochrane Injuries Group reported results of a meta-analysis of the available 
medical literature on “Human albumin solution for resuscitation and volume expansion 
in critically ill patients” and concluded that for patients with hypovolaemia there is no 
evidence that albumin reduces mortality when compared with cheaper alternatives 
such as saline. Contributing significantly to this report were results from the SAFE 
trial (Saline vs Albumin Fluid Evaluation) which compared the safety and efficacy of 
albumin versus saline in Australasian intensive care units. The study concluded that 
albumin and saline should generally be considered clinically equivalent treatments for 
intravascular resuscitation in the ICU although further study is required for more highly 
selected populations of critically ill patients, for example those with brain injury. The 
Cochrane report also concluded that for patients with burns and hypoalbuminaemia 
there is no evidence that albumin reduces mortality. Due to the increased cost of 
albumin compared to alternatives such as saline, albumin should only be used within 
the context of further trials.
5.3.2   Albumex® 20 (Human albumin 20%)
Albumex® 20 contains 200 g/L albumin in solution for intravenous injection and is 
hyperoncotic and hypo-osmotic compared to human serum. It is available in vials 
of 10 mL and 100 mL volume. When infused it supplies the oncotic equivalent 
of approximately four times its volume of human plasma. Albumex® 20 has two 
main functions: maintenance of plasma colloid osmotic pressure and transport of 
intermediate products in the transport and exchange of tissue metabolites. It is 
prepared by a combination of Cohn cold-ethanol fractionation and chromatography. 
The manufacturing process of Albumex® 20 includes pasteurisation and cold 
temperature incubation to reduce the potential for viral transmission. The current 
procedures are effective for inactivation/removal of HIV, hepatitis A, hepatitis B, and 
hepatitis C and may also be of limited value against parvovirus B19.
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Indications for Use
Table 5.12: Clinical Indications for Use of Albumex® 20
Indication
Comments
Hypoproteinaemia in  ■   Administered when there are (or it is anticipated) clinical 
acutely ill patients
problems or complications from reduced oncotic 
pressure, and/or as an adjunct to diuretic therapy.
Shock
■ 
 May be used for the resuscitation of patients in shock 
due to acute loss of blood or plasma however 4% 
human albumin is preferred when available. 
Burns
■ 
 Extensive burns are followed by sequential shifts in the 
distribution of body water, salt and proteins resulting in 
hypovolaemic shock and circulatory failure.
■ 
 Initially there is an increased vascular permeability 
leading to loss of water and proteins into 
the extravascular compartment leading to 
haemoconcentration. 
■ 
 Large volumes of crystalloid solutions should be infused 
to restore the constricted intravascular fluid space 
while smaller amounts of Albumex® 20 are required to 
maintain adequate plasma volume and colloid osmotic 
pressure.
Haemodialysis
■ 
 May be used to assist with the rapid removal of excess 
extravascular fluid and to maintain perfusion pressure.
Adult Respiratory 
■ 
 ARDS, an acute inflammatory lung injury with diffuse 
Distress Syndrome 
alveolar damage and increased vascular permeability, is 
 
characterised by inadequate oxygenation secondary to 
non-cardiogenic pulmonary oedema.
■ 
 Combination therapy with Albumex® 20 and diuretics 
may improve fluid balance, oxygenation, and 
haemodynamics.
■ 
 In patients who have undergone abdominal surgery, 
intravenous administration of 20% albumin immediately 
after the operation has been shown to improve lung 
compliance and gaseous exchange.
Therapeutic plasma 
■ 
 TPE is a procedure in which approximately one plasma 
exchange
volume is exchanged with a colloid replacement 
solution. The choice of replacement fluid and its 
concentration are determined by the particular clinical 
situation and the frequency of the procedure.
■ 
 Iso-oncotic 4% albumin solution is the preferred 
replacement material. If the patient’s serum albumin 
level is not maintained 20% albumin may be indicated. If 
exchange occurs less frequently than once a week, less 
concentrated colloids may be appropriate.
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Precautions
■  
Adverse effects 
 
Adverse reactions to albumin solutions are uncommon and are usually mild and 
transient. Chills, fever, urticaria, flushing, nausea, headache and dyspnoea may 
occur. More serious allergic events including hypotension and anaphylaxis are 
reported. Hypotension has been reported in patients given albumin who are on 
angiotensin-converting enzyme (ACE) inhibitors.
■  
Aluminium accumulation 
 
Albumex® 20 contains trace amounts of aluminium (≤ 200 µg/L). Accumulation 
of aluminium in patients with chronic renal insufficiency has led to toxic 
manifestations such as hypercalcaemia, vitamin D-refractory osteodystrophy, 
anaemia and severe progressive encephalopathy. Therefore, when large 
volumes of albumin are contemplated for administration to such patients, 
serious consideration should be given to these potential risks relative to the 
anticipated benefits.
■  
Circulatory overload 
 
The colloid osmotic effect of Albumex® 20 is approximately four times that of 
plasma. Circulatory overload can be avoided by monitoring the rate and volume 
of infusion. Patients with cardiac failure, renal insufficiency or stabilised chronic 
anaemia often have an increased circulatory plasma volume and are at special 
risk of developing circulatory overload.
■  
Compatibility with other fluids 
 
Albumex® 20 should not be mixed with protein hydrolysates, amino acid 
solutions, solutions containing alcohol, or solutions containing drugs that bind 
to albumin such as calcium channel blockers.
■  
Hyperoncotic effects 
 
As Albumex® 20 is hyperoncotic, it must be diluted with or followed by crystalloid 
solution in the presence of dehydration or shock.
 
If Albumex® 20 is diluted to an iso-oncotic protein concentration (4-5% albumin) 
prior to administration, this must be done with an iso-osmotic electrolyte solution 
such as 0.9% saline. Under no circumstances should water be used since the 
lower tonicity will lead to intravascular haemolysis.
■  
Hypoproteinaemia 
 
The infusion of Albumex® 20 is not justified in hypoproteinaemic states associated 
with chronic cirrhosis, malabsorption, protein losing enteropathies, pancreatic 
insufficiency, undernutrition. Albumex® 20 may be indicated as a temporising 
measure in selected cases awaiting liver transplantation.
■  
Nephrosis 
 
In chronic nephrosis, infused albumin is promptly excreted by the kidneys with 
no or limited relief of the chronic oedema. Albumex® 20 may be indicated as a 
temporising measure in selected cases awaiting renal transplantation.
■  
Shock    
Administration of albumin can aggravate myocardial depression when present 
in patients with shock.
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■  
Sodium levels  
The sodium levels in this product are 48 - 100 mmol/L. This should be noted 
when the product is used in patients requiring sodium restriction.
5.4  
Immunoglobulin Preparations
General Considerations 
Immunoglobulin products are sterile, preservative-free solutions of concentrated IgG 
prepared by Cohn cold-ethanol fractionation and chromatography of human plasma. 
In the case of specific immunoglobulins, for example anti-D immunoglobulin and 
hepatitis B immunoglobulin, plasma is obtained from individuals with a high titre of 
the required antibody. 
The manufacturing process contains two or more viral removal steps such as 
pasteurisation (inactivation) and viral filtration (nanofiltration) reducing the possibility of 
virus transmission. Currently available immunoglobulins have not been implicated in the 
transmission of viral infectious diseases including human immunodeficiency virus (HIV). 
Precautions
■  
Immunoglobulin products approved for intramuscular injection must not be 
administered intravenously because of the potential for severe adverse reactions. 
They should be given slowly by deep intramuscular injection using an appropriate 
sized needle and care should be taken to draw back on the plunger of the syringe 
before injection in order to be certain that the needle is not in a blood vessel.
■  
If an intramuscular dose of more than 5 mL is required, it is advisable to 
administer in divided doses at different sites. Hyaluronidase and/or a suitable 
local anaesthetic may be added to the injection if desired. When large doses 
of immunoglobulins are required, consider using an alternative product suitable 
for intravenous administration. 
■  
Intramuscular injection of immunoglobulin products should be avoided in 
patients with a low platelet count. In these circumstances they may be given 
subcutaneously.
■  
Immunoglobulin products approved for subcutaneous infusion must not be 
administered intravenously because of the potential for severe adverse reactions.
■  
Immunoglobulin products should be given with caution to patients with a 
history of prior systemic allergic reactions following the administration of human 
immunoglobulin preparations. In the case of allergic shock, treatment should 
follow recommended guidelines for managing anaphylaxis.
Contraindications
Immunoglobulin products are contraindicated in individuals:
■  
With isolated immunoglobulin A (IgA) deficiency, unless they have been tested 
and shown not to have circulating anti-IgA antibodies.
■  
Who have severe thrombocytopenia or any coagulation disorder that would 
contraindicate intramuscular injection.
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Interactions with Other Drugs
■  
Immunoglobulin should not be mixed with other pharmaceutical products, 
except as indicated by the manufacturer.
■  
Passively acquired antibody can interfere with the response to live, attenuated 
virus vaccines. Therefore, administration of such vaccines, e.g., measles and 
varicella, should be deferred for at least 3 months after passive immunisation 
with immunoglobulin preparations and antibody-containing blood components, 
i.e., whole blood, resuspended red cells, plasma and platelets. General 
Recommendations on Immunization 
from the Advisory Committee on 
Immunization Practices (ACIP), including recommended deferral intervals, are 
available from the Centers for Disease Control and Prevention (CDC) at www.
cdc.gov/vaccines/. Consultation with a NZBS Transfusion Medicine Specialist/
Medical Officer is recommended.
■  
By the same token, immunoglobulins and antibody-containing blood components 
should not be administered for at least two weeks after a live vaccine has been 
given.
■  
Inactivated vaccines may be administered concurrently with passive antibody 
(although in separate syringes) to induce active immunity, as is sometimes done 
for tetanus-prone wounds.
Passive Transfer of Antibodies and Interference with Serological Testing 
After injection of immunoglobulin, the transient rise of the various passively transferred 
antibodies in the patient’s blood may result in misleading positive results in serological 
testing. Although it has not been determined whether or not immunoglobulin products 
can transmit human parvovirus B19, they are known to contain antibodies to the virus.
Adverse Reactions 
■  
Local tenderness, erythema and stiffness may occur at the site of injection and 
may persist for several hours. This may occur after any intramuscular injection. 
■  
Mild pyrexia, malaise, drowsiness and urticaria have occasionally been reported 
after injections of immunoglobulins. 
■  
True allergic responses are rare. Skin lesions, headache, dizziness, nausea, 
generalised hypersensitivity reactions and convulsions have been reported on 
rare occasions. These occur more frequently in patients who have a profound 
hypogammaglobulinaemia. 
5.4.1   Normal Immunoglobulin-VF
Normal Immunoglobulin-VF is a sterile, preservative-free solution containing 160 mg/
mL human plasma proteins with at least 98% being immunoglobulin (mainly IgG). 
Normal Immunoglobulin-VF is intended for intramuscular injection.
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Indications for Use
Table 5.13: Clinical Indications for Use of Normal Immunoglobulin-VF
Indication
Comments
Primary 
Congenital and acquired forms.
hypogammaglobulinaemia
Secondary 
Acquired hypogammaglobulinaemia, as seen in 
hypogammaglobulinaemia haematological malignancies, nephrosis or protein-
losing enteropathy, complicated by recurrent 
infections.
Hepatitis A
Routine passive protection is recommended in those 
exposed less than two weeks previously for the 
following categories of individuals: 
■ 
 Household contacts of an index case who have 
not already had hepatitis A or have no evidence of 
immunity to the virus
■ 
 Common source exposures (i.e., a vehicle such 
as food or water is identified as a common source 
of infection for multiple cases of hepatitis) where 
administration of Normal Immunoglobulin-VF 
should be considered for all those exposed
■ 
Institutional contacts
■ 
Staff in institutions where hepatitis is endemic 
■ 
 Newborn infants where the mother has developed 
acute hepatitis A from two weeks before birth to 
one week after birth 
Routine prophylaxis is not recommended for school, 
factory or hospital contacts. Active immunisation 
with hepatitis A vaccine is recommended in these 
circumstances. 
Vaccination is also recommended for those at risk of 
exposure to hepatitis A, such as persons travelling to 
areas of high or intermediate endemicity and staff at 
child day care centres. 
Immunoglobulin is no longer routinely recommended 
for pre-travel use however may be appropriate for 
providing optimal protection to adults aged over 40 
years of age, immunocompromised individuals and 
those with chronic medical conditions including liver 
disease who are planning to depart in < 2 weeks. 
Travellers under 12 months of age and those unable 
or unwilling to receive vaccination should also receive 
immunoglobulin.
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Table 5.13: Clinical Indications for Use of Normal Immunoglobulin-VF continued
Indication
Comments
Rubella
Although Normal Immunoglobulin-VF can prevent 
or modify the clinical disease in susceptible rubella 
contacts if given within 72 hours of exposure, it does 
not prevent viraemia in such patients. It should not be 
relied upon to prevent congenital malformations due to 
rubella if given to susceptible pregnant women during 
the first trimester. Therefore, routine use of Normal 
Immunoglobulin-VF for post-exposure prophylaxis of 
rubella in early pregnancy is not recommended. It may 
be considered if termination of the pregnancy is not 
an option but termination must be discussed when 
maternal infection is confirmed.
Measles
Recommended for the following contacts of measles 
cases: 
■ 
 Immune-compromised or immune-deficient 
children 
■ 
Pregnant women 
■ 
 Immune-competent children aged under 15 
months beyond 72 hours after exposure 
■ 
 People outside the 72-hour window for MMR who 
have not had a history of measles infection or 
vaccination 
For these individuals Normal Immunoglobulin-VF is 
given to attenuate disease and should be given as 
soon as possible, to a maximum of six days after 
exposure.
Poliomyelitis  
Normal Immunoglobulin-VF is recommended for 
 
susceptible contacts not previously immunised against 
poliomyelitis.
In general, the earlier in the incubation period of hepatitis A, rubella, measles or 
poliomyelitis that normal immunoglobulin is given, the greater its effectiveness.
Transfusion Medicine Handbook 3rd Edition 
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Dosage and Administration
Table 5.14: Dosage Recommendations for Normal Immunoglobulin-VF
Indication
Dose 
Dose Interval (months)
(mL/kg)
Hepatitis A
■ 
Short-term prophylaxis (general) 
0.03
■ 
Long-term prophylaxis (general)
0.06
5 monthly1
■ 
Short term travel (< 3 months)
0.03
■ 
Long term travel2 (> 3 months)
0.06
Repeat 4-6 monthly 
■ 
Institutional contacts2 
0.06
■ 
Institutions where hepatitis A endemic2
0.06
Repeat 6 monthly
Hypogammaglobulinaemia
0.6
Additional loading dose in 
first month, then monthly
Measles prophylaxis3
0.6
Poliomyelitis
0.3
Rubella
0.2
1Perform serological checks to assess if active immunity has developed.
2 Use of hepatitis A vaccine may be more appropriate for these individuals provided there is sufficient time 

for active immunity to develop (7–10 days).
3 0.6 mL/kg to a maximum dose of 5 mL in immune-competent infants aged under 15 months and to a 
maximum dose of 15 mL, recommended as three 5 mL injections, in pregnant women, immune-competent 
adults and immune-compromised or immune-deficient children.

5.4.2   Hepatitis B Immunoglobulin-VF
Hepatitis B Immunoglobulin-VF is a sterile, preservative-free solution containing not less 
than 100 IU/mL neutralising hepatitis B antibodies. Donations used in the preparation 
of Hepatitis B Immunoglobulin-VF are selected on the basis that they contain high 
levels of specific antibodies against HBsAg. Hepatitis B Immunoglobulin-VF is provided 
as 400 IU vials, intended for intramuscular injection.
Indications for Use 
Hepatitis B Immunoglobulin-VF is indicated for:
■  
Post-exposure prophylaxis in persons who did not receive prior vaccination or 
whose vaccination regimen is incomplete, or when the hepatitis B antibody level 
is inadequate (< 10 IU/L) 
■  
Infants born to HBsAg-positive mothers, either chronic carriers or those who 
contract hepatitis B during pregnancy 
■  
Patients with hepatitis B undergoing a liver transplant, to protect the transplanted 
liver 
Post-exposure prophylaxis should be considered fol owing percutaneous or 
permucosal exposure to HBsAg-positive or suspected HBsAg-positive material, for 
example, following needle stick injury, oral ingestion or sexual exposure.
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Dosage and Administration 
For maximum protective effect, Hepatitis B Immunoglobulin-VF should be given within 
72 hours of exposure. Efficacy is greatly reduced if it is given after a longer interval. 
Table 5.15: Prophylaxis with Hepatitis B Immunoglobulin-VF in Adults Following 
Percutaneous or Permucosal Exposure to HBsAg-positive or Suspected 
HBsAg-positive Material

Source material
Vaccination history
No prior vaccination or 
Completed vaccination 
incomplete vaccination 
regimen
regimen
Confirmed 
A single dose of 400 IU 
Test for anti-HBs. If level <10 
positive for 
hepatitis B immunoglobulin 
IU/L, give a single dose of 400 
HBsAg
immediately and initiate 
IU hepatitis B immunoglobulin 
hepatitis B vaccination 
immediately plus a booster 
regimen at the same time.
vaccination.
High risk for 
Initiate hepatitis B vaccination 
Test exposed person for HBs 
HBsAg but not 
regimen. Test source material 
antibody. If level <10 IU/L, test 
confirmed
for HBsAg and, if positive, 
source material for HBsAg 
give a single dose of 400 IU 
and, if positive, give a single 
hepatitis B immunoglobulin.
dose of 400 IU Hepatitis B 
Immunoglobulin-VF plus a 
booster vaccination.
Uncertain or low 
Initiate hepatitis B vaccination 
Nothing required.
risk
regimen.
Active immunisation with hepatitis B vaccine should always be commenced in 
conjunction with administration of Hepatitis B Immunoglobulin-VF in patients exposed 
to hepatitis B virus. Vaccination should be initiated simultaneously with the passive 
immunoglobulin, but administered at a different site.
Prophylaxis in Infants Born to HBsAg-positive Mothers
Where HyperHEP™ S/D is unavailable, give 100 IU Hepatitis B Immunoglobulin-VF 
to the infant at birth and initiate simultaneously a hepatitis B vaccination regime 
administered at a different site.
5.4.3   HyperHEP™ S/D
HyperHEP™ S/D is a sterile, preservative-free, solvent/detergent-treated solution 
containing not less than 220 IU/mL neutralising hepatitis B antibodies. Donations used 
in the preparation of HyperHEP™ S/D are selected on the basis that they contain high 
levels of specific antibodies against HBsAg. HyperHEP™ S/D is supplied as a 0.5 mL 
neonatal single-dose syringe containing at least 110 IU of hepatitis B immunoglobulin, 
intended for intramuscular injection.
Indications for Use 
HyperHEP™ S/D is indicated for:
■  
Infants born to HBsAg-positive mothers, either chronic carriers or those who 
contract hepatitis B during pregnancy
Transfusion Medicine Handbook 3rd Edition 
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Dosage and Administration
The infant should receive a single 110 IU neonatal dose of HyperHEP™ S/D at birth. 
The dose is preferably given within 12 hours of birth as efficacy decreases markedly 
if treatment is delayed beyond 48 hours. Hepatitis B vaccine should be administered 
concurrently with hepatitis B immunoglobulin (or at most within 7 days) but at a 
separate site. If administration of the first dose of hepatitis B vaccine is delayed for 
as long as 3 months, then a 0.5 mL dose of HyperHEP™ S/D should be repeated 
at 3 months. If vaccine is refused, the 0.5 mL dose of HyperHEP™ S/D should be 
repeated at 3 and 6 months. 
5.4.4   Tetanus Immunoglobulin-VF
Tetanus Immunoglobulin-VF is a sterile, preservative-free, pasteurised solution with a 
tetanus antitoxin activity of not less than 100 IU/mL. Donations used in the preparation 
of tetanus immunoglobulin are selected on the basis that they contain high levels of 
specific antibodies against the toxin of Clostridium tetani. Tetanus Immunoglobulin-VF 
is intended for intramuscular injection.
Indications for Use 
Tetanus Immunoglobulin-VF is indicated for:
■  
Passive protection of individuals who have sustained a tetanus-prone wound 
and who have either not been actively immunised against tetanus or whose 
immunisation history is doubtful 
■  
Passive protection of fully immunised individuals with a tetanus-prone wound if 
more than 10 years have elapsed since the last dose of tetanus toxoid vaccine 
In both of the above instances, active immunisation with tetanus vaccine should be 
commenced at the same time. Although tetanus immunoglobulin and vaccine can 
be given at the same time, they should be administered in opposite limbs, using 
separate syringes.
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Table 5.16: Guide to Tetanus Prophylaxis in Wound Management
Type of wound
History 
Clean, minor wound
All other wounds
of active 
immunisation
Tetanus 
Tetanus 
Tetanus 
Tetanus 
Vaccine
Immunoglobulin-
Immunoglobulin-
1
VF
Vaccine1
VF
Never 
immunised or 
Yes
No
Yes
Yes
< 3 doses
Immunised and 
≥ 3 doses:
< 5 years since 
No
No
No
No
last dose
5-10 years 
No
No
Yes
No
since last dose
> 10 years 
Yes
No
Yes
Yes
since last dose
1 Children < 8 years old receive combined DTPa vaccine. Persons 8 years and older receive combined 
dT vaccine.
Dosage and Administration 
Good medical care is essential in the prevention of tetanus from fresh wounds. 
Thorough cleansing and removal of all foreign and necrotic material from the site of 
injury is important.
The minimum routine prophylactic dose of Tetanus Immunoglobulin-VF for adults or 
children is 250 IU given slowly by deep intramuscular injection. The dose should be 
doubled to 500 IU if the wound is grossly contaminated or if more than 24 hours have 
elapsed since injury or if there is a risk of heavy contamination or following burns.
An intravenous preparation of tetanus antitoxin is appropriate for patients where large 
doses are indicated (i.e., treatment of tetanus), or when the patient has a significant 
haemostatic defect which may cause bleeding following intramuscular injection. In New 
Zealand, Intragam® P is used to provide intravenous tetanus immunoglobulin. As the 
level of immunoglobulin in each batch varies consultation with an NZBS Transfusion 
Medicine Specialist/Medical Officer is recommended prior to prescription.
Treatment of Suspected or Confirmed Clinical Tetanus
For the treatment of suspected or confirmed clinical tetanus it is recommended that a 
single dose Intragam® P containing 4000 IU tetanus immunoglobulin is given to cover 
the typical 4-6 week course of the illness. NZBS acknowledges that the optimal dose, 
which may be as low as 500 IU, is not yet defined.
Transfusion Medicine Handbook 3rd Edition 
Page 83

5.4.5   Zoster Immunoglobulin-VF
Zoster Immunoglobulin-VF is a sterile, preservative-free solution containing not 
less than 200 IU/vial varicella-zoster antibody. Plasma for Zoster Immunoglobulin-
VF is obtained from blood donors who have recently recovered from shingles or 
chickenpox. Donations are selected on the basis that they contain high levels of 
antibodies against Herpesvirus varicellae. Zoster Immunoglobulin-VF is intended for 
intramuscular injection.
Indications for Use
Zoster Immunoglobulin-VF is indicated for prophylaxis against varicella in patients who 
meet all of the following four criteria listed below.
Table 5.17: Clinical Indications for the Use of Zoster Immunoglobulin-VF
Criteria
Required Condition(s)
One of the following underlying 
■ 
 Neoplastic disease (leukaemia or lymphoma)
illnesses or conditions:
■ 
 Congenital or acquired immune compromise
■ 
 Immunosuppressive therapy with steroids or 
antimetabolites
■ 
 Pregnancy in non-immune woman
One of the following types of 
■ 
 Household contact
exposure to chickenpox or 
■ 
 Playmate contact (> 1 hour play indoors)
shingles patients:
■ 
 Hospital contact (in same 2 to 4 bedroom or 
adjacent beds in a large ward)
■ 
 Newborn contact (newborn of mother who 
develops chickenpox (but not zoster) from 
7 days before to 7 days after delivery)
■ 
 Premature infant ≥ 28 weeks gestation 
whose mother lacks a prior history of 
chickenpox
■ 
 Premature infant < 28 weeks gestation or  
< 1000 g regardless of maternal history
Negative or unknown prior history 
of chickenpox
Zoster Immunoglobulin-VF can 
be given within 96 hours1 for best 
effect (however may be given up 
to 10 days post-exposure)
1 For guidance on the management of both pregnant women exposed to varicella or zoster and newborns 
exposed to maternal perinatal varicella or zoster, including recommendations on the timing of Zoster 
Immunoglobulin-VF administration in these situations, refer to the NZ Ministry of Health Immunisation 
Handbook.

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The Starship Children’s Health Clinical Guideline covering Zoster Immunoglobulin (2013) 
and the National Child Cancer Network Guideline for Immunisation of Children During 
and After Cancer Therapy
 (2013) provide additional specific detail on the use of zoster 
immunoglobulin in paediatric post-exposure prophylaxis and are summarised below. 
Consultation with a specialist paediatrician or NZBS Transfusion Medicine Specialist/
Medical Officer is recommended prior to prescription.
Table 5.18:  Recommendations for the Use of Zoster Immunoglobulin in Children at 
Risk for Developing Serious Varicella Infection and Complications
At Risk Group
Comments
Considered as 
High dose corticosteroid therapy
> 0.5 mg/kg/day of prednisone or 
equivalent within the last three months.
Receiving immunosuppressive 
All children regardless of VZV IgG status.
treatment or chemotherapy
For 3 months after therapy if VZV IgG negative.
Completed immunosuppressive 
Regardless of VZV IgG status:
treatment or chemotherapy1
- for 6 months after autologous HPC transplant.
- for 12 months2 after allogeneic HPC transplant.
Malignancy
Congenital immunodeficiency
HIV positive; no prior history of 
chickenpox
1 Patients who have received antithymocyte globulin, alemtuzumab, fludarabine or other T-cell 
immunomodulation should be discussed with a paediatric oncologist.
2May be longer if chronic GVHD is present.
Varicella-zoster immunoglobulin is of no value in the treatment of established varicella 
or zoster infection. High levels of circulating antibody do not prevent dissemination 
of infection.
Dosage and Administration
The required dose is 125 IU per 10 kg bodyweight and rounded up to the nearest 
200 IU to a maximum of 600 IU.
Table 5.19: Weight-Based Dosing Schedule for Zoster Immunoglobulin-VF 
Weight of Patient (kg)
Dose (IU)
No. of Vials
0 - 10
125
1
 
10.1 - 20
250
2
 
20.1 - 30
375
2
 
30.1 - 40
500
3
>40
600
3
Transfusion Medicine Handbook 3rd Edition 
Page 85

An intravenous preparation of varicella-zoster immunoglobulin is appropriate when 
the patient has a significant haemostatic defect which may cause bleeding following 
intramuscular injection. In New Zealand, Intragam® P is used to provide intravenous 
varicella-zoster immunoglobulin. As the level of immunoglobulin in each batch 
varies, consultation with an NZBS Transfusion Medicine Specialist/Medical Officer is 
recommended prior to prescription.
5.4.6   Berirab® P (Rabies immunoglobulin)
Berirab® P does not have full New Zealand registration and so consultation with an 
NZBS Transfusion Medicine Specialist/Medical Officer is required prior to product 
release.
Berirab® P is a sterile solution of anti-rabies immunoglobulin prepared from the plasma 
of individuals immunised with rabies vaccine. Donations are selected on the basis that 
they contain high levels of rabies antibody. Each 1 mL of Berirab® P contains a minimum 
of 150 IU/mL of rabies antibody. Berirab® P should be administered intramuscularly.
If anatomically feasible, the full dose should be thoroughly infiltrated in the area around 
and into the wounds. Any remaining volume should be injected intramuscularly at a 
site distant from vaccine administration.
Indications for Use
Berirab® P is indicated for prophylaxis in individuals suspected of having exposure 
to rabies from:
■  
Bites, licks, scratches or other injuries caused by a suspected rabid animal 
■  
Mucous membrane contamination with infectious tissue or saliva of suspected 
rabid animal
■  
Mucous membrane or new skin wound contact with rabies live attenuated 
vaccine (e.g., vaccination baits)
The exception to these indications is individuals who have previously been immunised, 
pre- or post-exposure, with rabies vaccine prepared from human diploid cells.
The recommended dose of Berirab® P is 20 IU per kg body weight which should be 
given in conjunction with rabies vaccine.
5.4.7   Rh(D) Immunoglobulin-VF (Anti-D immunoglobulin)
Rh(D) Immunoglobulin-VF is a sterile, preservative-free solution with an anti-D antibody 
content of either 625 IU or 250 IU per vial. Rh(D) Immunoglobulin-VF is prepared from 
plasma obtained from either New Zealand voluntary or USA remunerated donors who 
have been immunised to the RhD antigen. Rh(D) Immunoglobulin-VF is intended for 
deep intramuscular injection using an appropriate sized needle.
Anti-D immunoglobulin acts by suppressing the immune response of RhD negative 
individuals exposed to RhD positive red cells. Such exposure follows the passage of 
cells from the fetal to the maternal circulation or the transfusion of RhD positive red 
cells. Clinical studies indicate that the administration of anti-D immunoglobulin to a 
RhD negative mother within 72 hours of the birth of a RhD positive infant reduces 
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the incidence of RhD isoimmunisation from 12 - 13% to 1 - 2%. Studies have also 
shown that this number can be reduced to < 1.0% by antenatal prophylaxis with anti-D 
immunoglobulin administered at 28 and 34 weeks of pregnancy.
Indications for Use 
Rh(D) Immunoglobulin-VF is indicated for:
■  
Prevention of RhD sensitisation in RhD negative females with child-bearing 
potential
Rh(D) Immunoglobulin-VF may, in certain circumstances, also be used for protection 
against the development of anti-D sensitisation when RhD positive donor red cells 
are transfused to RhD negative females without child-bearing potential and to RhD 
negative males.
Precautions
There is some evidence to suggest that intramuscular administration of anti-D 
immunoglobulin may be associated with an increased risk of lack of effect in patients 
with a body mass index (BMI) > 30. An Expert Panel Consensus Position Statement 
(available online at www.transfusion.com.au/node/612) provides recommendations 
regarding the use of anti-D immunoglobulin in these patients.
Contraindications 
Rh(D) Immunoglobulin-VF should not be given to RhD positive individuals or to RhD 
negative individuals previously sensitised to the RhD antigen.
Rh(D) Immunoglobulin-VF should not be given to RhD negative women with 
detectable anti-D except where the antibody is passively acquired due to prior 
antenatal administration. If unsure whether the anti-D detected in the mother’s blood 
is passively acquired or preformed, the treating clinician and/or a NZBS Transfusion 
Medicine Specialist/Medical Officer should be consulted. If there is continuing doubt, 
Rh(D) Immunoglobulin-VF should be administered. Although there is no benefit in 
administering Rh(D) Immunoglobulin-VF to a woman who is already sensitised to RhD 
antigen, there is no more risk than when it is given to a woman who is not sensitised.
Dosage and Administration: Antenatal and Postpartum Prophylaxis
The following table is based on the 2003 Australian National Blood Authority (NBA) 
Guidelines on the Prophylactic Use of RhD Immunoglobulin (Anti-D) in Obstetrics and 
the 2013 British Committee for Standards in Haematology Guideline for the Use of 
Anti-D Immunoglobulin for the Prevention of HDFN.
 The table below is reproduced, 
together with additional explanatory notes, in Section 6.8: Hemolytic Disease of the 
Fetus and Newborn (HDFN) 
of this Handbook. In 2011 the Royal Australian and New 
Zealand College of Obstetricians and Gynaecologists (RANZCOG) endorsed the 2003 
NBA Guidelines, however it should be noted that the NZ Ministry of Health does not 
recommend routine antenatal anti-D prophylaxis (RAADP).
Transfusion Medicine Handbook 3rd Edition 
Page 87

Table 5.20: Indications for the Use of Anti-D Immunoglobulin for the Prevention of 
HDFN (unless the fetus is confirmed to be RhD negative)

Timing
Clinical Indication 
Routine antenatal 
A RhD negative woman, not previously immunised 
prophylaxis1
to produce anti-D; one dose at each of 28 and 34 
weeks gestation.2 
Anti-D immunoglobulin dose: 625 IU (125 µg)
Potential sensitising event  A RhD negative woman, not previously immunised to 
during first trimester up 
produce anti-D, with an obstetric indication.
to and including 12 weeks  ■   Uterine bleeding where this repeated, heavy or 
gestation
associated with abdominal pain3
■ 
 Miscarriage3
■ 
 Termination of pregnancy
■ 
 Ectopic pregnancy
■ 
 Molar pregnancy
Anti-D immunoglobulin dose: 250 IU (50 µg)4
Potential sensitising 
A RhD negative woman, not previously immunised to 
event beyond first 
produce anti-D, with an obstetric indication.
trimester5
■ 
 Amniocentesis, chorionic villus sampling, and 
intrauterine fetal blood sampling
■ 
 Antepartum haemorrhage (or unexplained 
uterine pain)
■ 
 External cephalic version (performed or 
attempted)
■ 
 Abdominal trauma sufficient to cause FMH
■ 
 Ectopic pregnancy
■ 
 Molar pregnancy
■ 
 Intrauterine death or stillbirth
■ 
 Miscarriage, threatened miscarriage
■ 
 Termination of pregnancy
Anti-D immunoglobulin dose: 625 IU (125 µg)
Postpartum prophylaxis6
A RhD negative woman, not previously immunised 
to produce anti-D, who gives birth to a RhD positive 
baby.
Anti-D immunoglobulin dose: 625 IU (125 
µg) with additional dose(s) indicated where 
fetomaternal haemorrhage is > 6 mL fetal red 

cells
1 Routine antenatal anti-D prophylaxis (RAADP) should be administered regardless of, and in addition to, 
prophylaxis given for a potentially sensitising event.
2 A sample for antibody testing should be taken prior to administration of anti-D immunoglobulin at 28 weeks.
3 Before 12 weeks gestation, in cases of either spontaneous complete miscarriage where the uterus is 

not instrumented or mild painless vaginal bleeding, the risk of fetomaternal haemorrhage is negligible.
4 For multiple pregnancies the recommended anti-D immunoglobulin dose is 625 IU (125 µg).
5 Routine antenatal prophylaxis does not preclude prophylaxis for a potentially sensitising event. 
6 Routine antenatal prophylaxis or prophylaxis for a potentially sensitising event does not preclude postpartum 

prophylaxis.
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NZBS is aware that an alternative approach to RAADP may be to administer a single 
1500 IU anti-D dose at 28 weeks, however this is currently not endorsed in NZ.
Dosage and Administration: Transfusion of RhD Positive Blood Components
The recommended dose of Rh(D) Immunoglobulin-VF is 100 IU per mL RhD positive 
red cells. A single 625 IU dose of Rh(D) Immunoglobulin-VF will therefore suppress the 
immune response induced by up to 6 mL of RhD positive red cells. Consultation with 
a NZBS Transfusion Medicine Specialist/Medical Officer is recommended in the event 
that a recipient has been transfused with a larger volume of RhD positive red cells. 
The amount of red cell contamination in platelet components supplied by NZBS is less 
than 1 mL per unit and therefore adequately covered by a single 250 IU dose of Rh(D) 
Immunoglobulin-VF. A single 250 IU dose of Rh(D) Immunoglobulin-VF (administered 
subcutaneously in severely thrombocytopenic patients) is likely to be sufficient to cover 
up to five adult therapeutic doses of RhD positive platelets given within a 6-week period.
5.4.8   Rhophylac® (Anti-D immunoglobulin)
Rhophylac does not have full New Zealand registration and so consultation with an 
NZBS Transfusion Medicine Specialist is required prior to product release.
Rhophylac® is a sterile, preservative-free solution in a pre-filled 2 mL syringe containing 
1500 IU (300 µg) anti-D IgG immunoglobulin. Rhophylac® is manufactured from plasma 
obtained from remunerated donors who have been immunised to the RhD antigen. It is 
important to note that this product is obtained from a screened and carefully monitored 
donor pool and has a similar safety profile to Rh(D) Immunoglobulin-VF. Rhophylac® 
may safely be administered intramuscularly or intravenously.
Indications for Use 
Rhophylac® has similar indications and contraindications for use as other anti-D 
immunoglobulin products. While Rhophylac® is an acceptable alternative to Rh(D) 
Immunoglobulin-VF, it is supplied by NZBS only when stock of this product is unavailable, 
large doses of anti-D are indicated (i.e., > 2 vials 625 IU Rh(D) Immunoglobulin-VF), or 
when a product suitable for intravenous administration is required.
Dosage and Administration 
A maximum dose of 15,000 IU is sufficient in the case of larger incompatible 
transfusions independent of whether the transfusion volume is greater than 
300 mL of RhD positive red cells. Treatment can usually be given without 
preceding exchange transfusion when the transfused RhD positive blood represents 
less than 20% of the total circulating red blood cells. If the volume exceeds 20%, 
consideration should be given to red cell exchange transfusion to reduce the load of 
RhD positive cells prior to Rhophylac® administration.
Precautions
■  
Following a large fetomaternal bleed or incompatible transfusion, patients 
receiving large doses of anti-D immunoglobulin should be monitored, as there 
is a risk of haemolytic reaction. To reduce this risk, the maximum recommended 
dose administration rate is 3000 IU every 8 hours.
■  
Rhophylac® can contain antibodies to other Rh antigens and the passive transfer 
Transfusion Medicine Handbook 3rd Edition 
Page 89

of these antibodies may be detectable by serological testing methods.
■  
There is some evidence to suggest that intramuscular administration of anti-D 
immunoglobulin may be associated with an increased risk of lack of effect 
in patients with a body mass index (BMI) > 30. An Expert Panel Consensus 
Position Statement (available online at www.transfusion.com.au/node/612) 
provides recommendations regarding the use of anti-D immunoglobulin in these 
patients. 
5.4.9   Intragam® P (Normal immunoglobulin, intravenous, IVIg)
Intragam® P is a sterile, preservative free solution containing 6 g of human protein and 
10 g of maltose in each 100 mL, available in 10 mL (0.6 g), 50 mL (3 g) and 200 mL 
(12 g) vials. The solution has a pH of 4.25 and isotonicity is achieved by the addition 
of maltose. Intragam® P is made by chromatographic fractionation of large pools of 
human plasma obtained from New Zealand’s voluntary and non-remunerated blood 
donors. Intragam® P is intended for intravenous administration.
The distribution of IgG subclasses present in Intragam® P is: IgG1 (61%), IgG2 (36%), 
IgG3 (3%) and IgG4 (1%). Intragam® P contains only trace amounts of IgA (typically 
<0.025 mg/mL). The actual amount of IgA in each batch is printed on the label. 
The protein has not been chemically or enzymatically modified and the manufacturing 
process contains specific steps to reduce the possibility of virus transmission including 
pasteurisation (heating at 60°C for 10 hours) and incubation at low pH.
Indications for Use  
Intragam® P is registered for use as replacement IgG therapy and immunomodulatory 
therapy for a number of conditions.
Table 5.21: Registered Indications for Use of Intragam® P
Indication
Comments
Replacement Therapy
■ 
 Primary immunodeficiency
Causing hypogammaglobulinaemia
■ 
 Acquired hypogammaglobulinaemia
Symptomatic with recurrent infections
 Immunomodulatory Therapy
■ 
 Primary immune thrombocytopaenia1
■ 
 Kawasaki disease
■ 
 Guillain-Barre syndrome
1 Recommendations for the use of IVIg in immune thrombocytopaenia (ITP) can be found in the International 
Consensus Report on the Investigation and Management of Primary Immune Thrombocytopenia in Blood 
2010; 115: 168-186 and the American Society of Hematology (ASH) 2011 Clinical Practice Guideline on 
the Evaluation and Management of Immune Thrombocytopenia.

In addition, intravenous immunoglobulin has an established and emerging therapeutic 
role in a wide range of, and in some cases uncommon or rare, autoimmune and 
inflammatory diseases including chronic inflammatory demyelinating polyneuropathy, 
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inflammatory myopathies, Lambert–Eaton myasthenic syndrome, multifocal motor 
neuropathy, myasthenia gravis, and stiff-person syndrome. Intragam® P is not 
registered for these indications in New Zealand and issue of this product is subject 
to consultation between the specialist physician and a NZBS Transfusion Medicine 
Specialist/Medical Officer.
Comprehensive evidence-based guidelines for the use of IVIg are lacking. Substitutes, 
such as the 2012 Australian National Blood Authority Criteria for the Clinical Use of 
Intravenous Immunoglobulin in Australia (2nd ed.)
 and the 2011 UK Department of 
Health Clinical Guidelines for Immunoglobulin Use (2nd ed. update) provide information 
about the criteria for accessing IVIg and should be followed wherever possible to avoid 
the inappropriate utilisation of Intragam® P.
Dosage and Administration 
Intragam® P may be infused undiluted. It may also be infused diluted with up to 2 parts 
of 0.9% saline or 5% glucose. 
■  
The infusion should be commenced at the rate of 1 mL per minute. 
■  
After 15 minutes the rate may be gradually increased to a maximum of 3 - 4 
mL per minute over a further 15 minutes. 
■  
Too rapid a rate of infusion may cause flushing and changes in heart rate and 
blood pressure.
■  
Patients naive to Intragam® P, switching from an alternative IVIg product, or who 
have not received IVIg for a long time, should be closely monitored during the 
first infusion.
■  
In patients at risk for acute renal failure or thromboembolic adverse reactions, 
IVIg products should be administered at the minimum rate of infusion and dose 
practicable.
Replacement Therapy
■  
The optimal dose and frequency of administration of Intragam® P must be 
determined for each patient. Freedom from recurrent bacterial infections is 
usually achieved with a serum IgG level > 5 g/L.
■  
Most patients initially receive 400 mg IgG per kilogram body weight, followed 
by monthly maintenance doses of at least 200 mg per kilogram body weight. 
■  
The monthly maintenance dose, guided by the patient’s clinical status and 
pre-infusion (trough) serum IgG level, is often 300 - 450 mg of IgG per kilogram 
body weight.
■  
As catabolic rates vary, the IgG levels of new patients should be monitored 
regularly for several monthly cycles to determine the effective dose.
Immunomodulatory Therapy
Primary immune thrombocytopaenia
■  
Patients should receive up to a maximum total cumulative dose of 2.0 g IgG 
per kilogram body weight, over 2 - 5 days.
Transfusion Medicine Handbook 3rd Edition 
Page 91

Kawasaki disease
■  
Patients should receive 1.6 - 2.0 g IgG per kilogram body weight, administered 
in divided doses over 2 - 5 days, or 2.0 g IgG per kilogram body weight as a 
single dose.
Guillain-Barre syndrome
■  
Patients should receive 0.4 g IgG per kilogram body weight per day for five days.
IVIg dosage recommendations for off-label indications are available in Criteria for the 
Clinical Use of Intravenous Immunoglobulin in Australia (2nd ed.)
, developed by the 
Australian National Blood Authority (NBA) in 2012.
Contraindications 
Intragam® P is contraindicated in individuals who have had a true anaphylactic reaction 
to the active substance or the excipient.
Precautions 
■  
Administration 
 
Intragam® P should only be administered intravenously. It is possible that 
Intragam® P may, on rare occasions, cause a precipitous fall in blood pressure 
and a clinical picture of anaphylaxis. Therefore, adrenaline and oxygen should 
be available for the treatment of such an acute reaction. 
■  
Aseptic meningitis 
 
Aseptic meningitis syndrome has been reported to occur infrequently in 
association with IVIg treatment.
■  
IgA antibodies  
 
Intragam® P contains trace amounts of IgA which may provoke anaphylaxis in 
patients with IgA antibodies, such as those with IgA deficiency. 
■  
Positive direct antiglobulin tests and red cell haemolysis 
 
Positive direct antiglobulin tests and red cell haemolysis have been reported 
following high dose infusion of intravenous immunoglobulin due to the presence 
of anti-A, anti-B, and occasionally with anti-D or other erythrocyte antibodies 
in the product. Such red cell sensitisation may cause crossmatching difficulties 
and transient haemolytic anaemia. 
■  
Renal dysfunction 
 
There have been reports of renal dysfunction and acute renal failure in patients 
receiving IVIg. Patients should be adequately hydrated prior to administration of IVIg.
■  
Thromboemblism 
 
Thrombotic events have been reported in association with IVIg therapy. Caution 
should be exercised in prescribing and administering Intragam® P in in patients 
with pre-existing risk factors for thrombotic events.
■  
Thrombophlebitis 
 
Prolonged administration (over 6 hours) using large doses (greater than 400 
mg/kg) may result in thrombophlebitis at the infusion site.
Page 92 
Transfusion Medicine Handbook 3rd Edition

Adverse Reactions 
Reactions to intravenous immunoglobulin tend to be related to the infusion rate and 
are most likely to occur during the first hour of the infusion. It is recommended that the 
patient’s vital signs and general status be monitored regularly throughout the infusion. 
The types of reactions that may occur include: malaise, abdominal pain, headache, 
chest-tightness, facial flushing or pallor, hot sensations, dyspnoea, non-urticarial skin 
rash, itching, arthralgia, tissue swelling, hypotension, nausea, or vomiting. Should 
any of these reactions develop during infusion of Intragam® P, the infusion should 
be temporarily stopped (5 - 10 minutes) until the patient improves clinically and then 
cautiously recommenced at a slower rate. 
Allergic reactions are most likely to occur during the first hour of the infusion.
True hypersensitivity reactions to intravenous immunoglobulin such as urticaria, 
angioedema, bronchospasm or hypotension occur very rarely. Should an anaphylactic 
reaction to Intragam® P develop, the infusion should be stopped and immediate 
treatment instituted with adrenaline and oxygen. 
Interactions with Other Medicines
Passively acquired antibody can interfere with the response to live attenuated virus 
vaccines such that vaccine administration should be deferred for at least 3 months. 
In the case of measles and varicella vaccines following IVIg products, the impairment 
may persist for up to 12 months. Where deferral is impractical, patients receiving 
such vaccines should have their antibody response checked. By the same token, 
immunoglobulins should not be administered for at least two weeks after live attenuated 
vaccines are given. Consultation with a NZBS Transfusion Medicine Specialist/Medical 
Officer is recommended.
Interaction with Capillary Glucose Measurement
Caution should be exercised when interpreting blood sugar levels in patients receiving 
Intragam® P. The maltose present in Intragam® P may result in falsely elevated capillary 
blood glucose levels with some types of glucose meters. If this measurement is used 
to guide treatment, hypoglycaemia may occur. 
When monitoring glucose levels in patients receiving Intragam® P, consult the product 
information and/or manufacturer of the glucose meter and test strips (including those 
used at home by patients) to ensure that maltose does not interfere with the blood 
glucose reading. 
5.4.10 Privigen® (Normal immunoglobulin, intravenous, IVIg) 
Privigen® is a sterile, preservative free 10% solution containing 10 g of human protein 
in each 100 mL, available in 50 mL (5 g), 100 mL (10 g) and 200 mL (20 g) vials. The 
solution has a pH of 4.8 and is approximately isotonic. The product contains 250 
mmol/L of L-proline as a stabiliser which is a physiological non-essential amino acid. 
It contains no carbohydrate stabiliser (e.g., sucrose, maltose) and has a low sodium 
content. Privigen® is made by a combination of cold ethanol fractionation, octanoic 
acid fractionation and anion exchange chromatography of large pools of human plasma 
obtained from blood donors in the United States and Europe. Privigen® is intended 
for intravenous administration.
Transfusion Medicine Handbook 3rd Edition 
Page 93

The distribution of IgG subclasses present in Privigen® is: IgG1 (68%), IgG2 (29%), 
IgG3 (2%) and IgG4 (1%). Privigen® contains only trace amounts of IgA (typically 
<0.025 mg/mL). 
The protein has not been chemically or enzymatically modified and the manufacturing 
process contains specific steps to reduce the possibility of virus transmission including 
filtration and incubation at low pH.
Indications for Use  
Privigen® is registered for use as replacement IgG therapy and immunomodulatory 
therapy for a number of conditions.
Table 5.22: Registered Indications for Use of Privigen®
Indication
Comments
Replacement Therapy
■ 
 Primary immunodeficiency1
Causing hypogammaglobulinaemia
■ 
 Acquired hypogammaglobulinaemia
Symptomatic with recurrent infections
Immunomodulatory Therapy2
■ 
 Primary immune thrombocytopaenia3, 4
■ 
 Kawasaki disease
■ 
 Guillain-Barré syndrome
■ 
 Chronic inflammatory demyelinating 
polyneuropathy
■ 
 Multifocal motor neuropathy
■ 
 Myasthenia gravis exacerbations
■ 
 Lambert-Eaton myasthenic syndrome
■ 
 Stiff person syndrome
1 The use of Privigen® has not been established in patients with primary immunodeficiency disorder under 
the age of 3 years.
2 The use of Privigen® has not been established in patients with neurological indications under the age of 
18 years.
3 Recommendations for the use of IVIg in immune thrombocytopaenia (ITP) can be found in the International 
Consensus Report on the Investigation and Management of Primary Immune Thrombocytopenia in Blood 
2010; 115: 168-186 and the American Society of Hematology (ASH) 2011 Clinical Practice Guideline on 
the Evaluation and Management of Immune Thrombocytopenia.

4 The use of Privigen® has not been established in patients with ITP under the age of 15 years.
In addition, intravenous immunoglobulin has an established and emerging therapeutic 
role in a wide range of other, and in some cases also uncommon or rare, autoimmune 
and inflammatory diseases. Privigen® is not registered in New Zealand for indications 
other than those listed. For situations involving off-label indications, issue of this product 
is subject to consultation between the specialist physician and a NZBS Transfusion 
Medicine Specialist/Medical Officer.
Comprehensive evidence-based guidelines for the use of IVIg are lacking. Substitutes, 
Page 94 
Transfusion Medicine Handbook 3rd Edition

such as the 2012 Australian National Blood Authority Criteria for the Clinical Use of 
Intravenous Immunoglobulin in Australia (2nd ed.)
 and the 2011 UK Department of 
Health Clinical Guidelines for Immunoglobulin Use (2nd ed. update) provide information 
about the criteria for accessing IVIg and should be followed wherever possible to avoid 
the inappropriate utilisation of Privigen®.
Dosage and Administration 
Privigen® may be infused undiluted. It may also be infused diluted with 5% glucose. 
■  
Patients naive to Privigen®, switching from an alternative IVIg product, or who 
have not received IVIg for a long time, should be closely monitored during and 
for the first hour after the first infusion.
■  
In such patients, the infusion should be commenced at the rate of 0.3 mL per 
kilogram body weight per hour. 
■  
If well tolerated, the rate may gradually be increased to 4.8 mL per kilogram 
body weight per hour. 
■  
In patients at risk for acute renal failure or thromboembolic adverse reactions, 
IVIg products should be administered at the minimum rate of infusion and dose 
practicable.
Replacement Therapy
■  
The optimal dose and frequency of administration of Privigen® must be 
determined for each patient. 
■  
Most patients receive 400 mg IgG per kilogram body weight initially, followed 
by monthly maintenance doses of at least 200 mg per kilogram body weight. 
■  
The monthly maintenance dose, guided by the patient’s clinical status, is often 
300 - 450 mg of IgG per kilogram body weight aiming for a pre-infusion (trough) 
serum IgG level of at least 4 - 6 g/L.
■  
As catabolic rates vary, the IgG levels of new patients should be monitored 
regularly for several monthly cycles to determine the effective dose. Three to 
six months are required for equilibration.
Immunomodulatory Therapy
Primary immune thrombocytopaenia
■  
Patients should receive up to a maximum total cumulative dose of 2.0 g IgG 
per kilogram body weight, over 2 - 5 days.
Kawasaki disease
■  
Patients should receive 1.6 - 2.0 g IgG per kilogram body weight, administered 
in divided doses over 2 - 5 days, or 2.0 g IgG per kilogram body weight as a 
single dose.
Transfusion Medicine Handbook 3rd Edition 
Page 95

Guillain-Barre Syndrome
■  
Patients should receive 0.4 g IgG per kilogram body weight per day for five 
days.
Chronic inflammatory demyelinating polyneuropathy
■  
Patients should receive a starting dose of 2.0 g IgG per kilogram body weight, 
administered in divided doses over 2 - 5 days.
■  
Patients should receive a maintenance dose of 1.0 g IgG per kilogram body 
weight, administered every three weeks.
Multifocal motor neuropathy
■  
Patients should receive a starting dose of 2.0 g IgG per kilogram body weight, 
administered in divided doses over 2 - 5 days.
■  
Patients should receive a maintenance dose of 0.4 - 2.0 g IgG per kilogram 
body weight, administered every two to six weeks.
Myasthenia gravis exacerbations
■  
Prior to surgery or during myasthenic crisis, patients should receive an induction 
dose of 1.0 - 2.0 g IgG per kilogram body weight, administered in divided doses 
over 2 - 5 days.
■  
Patients should receive a maintenance dose of 0.4 - 1.0 g IgG per kilogram 
body weight, administered every four to six weeks.
Lambert-Eaton myasthenic syndrome
■  
Patients should receive a starting dose of 2.0 g IgG per kilogram body weight, 
administered in divided doses over 2 - 5 days.
■  
Patients should receive a maintenance dose of 0.4 - 1.0 g IgG per kilogram 
body weight, administered every two to six weeks.
Stiff person syndrome
■  
Patients should receive a starting dose of 2.0 g IgG per kilogram body weight, 
administered in divided doses over 2 - 5 days.
■  
Patients should receive a maintenance dose of 1.0 - 2.0 g IgG per kilogram 
body weight, administered every four to six weeks.
IVIg dosage recommendations for off-label indications are available in Criteria for 
the Clinical Use of Intravenous Immunoglobulin in Australia (2nd ed.)
, developed 
by the Australian National Blood Authority (NBA) in 2012. In the case of allogeneic 
haematopoietic stem cell transplant, the following dosage recommendations for 
Privigen® have been used.
Treatment of infections and prophylaxis of graft-versus-host disease
■  
Patients should receive 0.5 g IgG per kilogram body weight weekly from 7 days 
before to 3 months after transplantation.
Persistent hypogammaglobulinaemia
■  
Patients should receive 0.5 g IgG per kilogram body weight monthly until antibody 
levels return to normal.
Page 96 
Transfusion Medicine Handbook 3rd Edition

Contraindications 
Privigen® is contraindicated in individuals who have had a true anaphylactic reaction 
to the active substance or the excipient and in those with hyperprolinaemia.
Precautions 
■  
Administration 
 
Privigen® should only be administered intravenously. IVIg may, on rare occasions, 
cause a precipitous fall in blood pressure and a clinical picture of anaphylaxis. 
Therefore, adrenaline and oxygen should be available for the treatment of such 
an acute reaction. 
■  
Aseptic meningitis 
 
Aseptic meningitis syndrome has been reported to occur infrequently in 
association with IVIg treatment.
■  
IgA antibodies  
 
Privigen® contains trace amounts of IgA which may provoke anaphylaxis in 
patients with IgA antibodies, such as those with IgA deficiency. 
■  
Positive direct antiglobulin tests and red cell haemolysis 
 
Positive direct antiglobulin tests and red cell haemolysis have been reported 
following high dose infusion of intravenous immunoglobulin due to the presence 
of anti-A, anti-B, and occasionally with anti-D or other erythrocyte antibodies 
in the product. Such red cell sensitisation may cause crossmatching difficulties 
and transient haemolytic anaemia. 
■  
Renal dysfunction 
 
There have been reports of renal dysfunction and acute renal failure in patients 
receiving IVIg. Patients should be adequately hydrated prior to administration of IVIg.
■  
Thromboembolism 
 
Thrombotic events have been reported in association with IVIg therapy. Caution 
should be exercised in prescribing and administering Privigen® in patients with 
pre-existing risk factors for thrombotic events.
Adverse Reactions 
Reactions to intravenous immunoglobulin tend to be related to the infusion rate and 
are most likely to occur during the first hour of the infusion. It is recommended that the 
patient’s vital signs and general status be monitored regularly throughout the infusion. 
The types of reactions that may occur include: malaise, abdominal pain, headache, 
chest-tightness, facial flushing or pallor, hot sensations, dyspnoea, non-urticarial 
skin rash, itching, arthralgia, tissue swelling, hypotension, nausea, or vomiting. 
Should any of these reactions develop during infusion of Privigen®, the infusion should 
be temporarily stopped (5-10 minutes) until the patient improves clinically and then 
cautiously recommenced at a slower rate. 
Allergic reactions are most likely to occur during the first hour of the infusion.
True hypersensitivity reactions to intravenous immunoglobulin such as urticaria, 
angioedema, bronchospasm or hypotension occur very rarely. Should an anaphylactic 
reaction to Privigen® develop, the infusion should be stopped and immediate treatment 
instituted with adrenaline and oxygen. 
Transfusion Medicine Handbook 3rd Edition 
Page 97

Interactions with Other Medicines
Passively acquired antibody can interfere with the response to live attenuated virus 
vaccines such that vaccine administration should be deferred for at least 3 months. 
In the case of measles and varicella vaccines following IVIg products, the impairment 
may persist for up to 12 months. Where deferral is impractical, patients receiving 
such vaccines should have their antibody response checked. By the same token, 
immunoglobulins should not be administered for at least two weeks after live attenuated 
vaccines are given. Consultation with a NZBS Transfusion Medicine Specialist/Medical 
Officer is recommended.
5.4.11 Evogam® (Normal immunoglobulin, subcutaneous, SCIg) 
Evogam® is a sterile, preservative free solution containing 16 g of human protein in 
each 100 mL, available in 5 mL (0.8 g) and 20 mL (3.2 g) vials. The solution has a 
pH of 6.6. As a stabiliser, Evogam® contains 2.25g of glycine in each 100mL. It does 
not contain a carbohydrate stabiliser (e.g., sucrose, maltose). Evogam® is made by 
chromatographic fractionation of large pools of human plasma obtained from New 
Zealand’s voluntary and non-remunerated blood donors. Evogam® is intended for 
subcutaneous administration.
The distribution of IgG subclasses present in Evogam® is: IgG1 (48-58%), IgG2 
(39-49%), IgG3 (1-2%) and IgG4 (1-2%). Evogam® contains only trace amounts 
of IgA (typically <0.025 mg/mL). The actual amount of IgA in each batch is printed 
on the label. 
The protein has not been chemically or enzymatically modified and the manufacturing 
process contains specific steps to reduce the possibility of virus transmission including 
pasteurisation (heating at 60°C for 10 hours) and nanofiltration. 
Indications for Use  
Evogam® is indicated in adults and children for replacement therapy in:
■  
Primary immunodeficiency diseases (PID)
■  
Symptomatic hypogammaglobulinaemia secondary to underlying disease or 
treatment
Dosage and Administration 
The dose and dosage interval must be individualised for each patient based on their 
measured IgG trough levels and ongoing clinical response. A weekly dose in the range 
0.05 - 0.15 g/kg body weight is recommended, corresponding to a total monthly dose 
of Evogam® in the range of 0.2 - 0.6 g/kg body weight.
Evogam® should be brought to room temperature and administered via the 
subcutaneous route, optionally at several infusion sites (advisable for large > 20 mL 
doses) and preferentially into the upper outer arm, upper thigh, abdomen or lateral hip 
at an initial infusion rate of 10 mL/hour. The infusion rate may be gradually increased 
after the first completed infusion up to 20 mL/hour. The maximum rate administered 
during clinical trials was 40 mL/hour using two infusion pumps simultaneously. Evogam® 
must not be administered intravenously. 
Page 98 
Transfusion Medicine Handbook 3rd Edition

Contraindications 
Evogam® is contraindicated in individuals who have had a true anaphylactic reaction 
to the active substance or to the excipient glycine.
Precautions 
■  
Administration 
 
Evogam® must only be administered subcutaneously. Other routes of 
administration have not been evaluated. Evogam® administered intravenously 
could cause a clinical picture of anaphylaxis. 
■  
Aseptic meningitis 
 
Aseptic meningitis syndrome has been reported to occur infrequently in 
association with human immunoglobulin treatment.
■  
IgA antibodies  
 
Evogam® contains trace amounts of IgA which may provoke anaphylaxis in 
patients with IgA antibodies, such as those with IgA deficiency.
■  
Positive direct antiglobulin tests and red cell haemolysis 
 
Evogam® can contain blood group antibodies causing a positive direct 
antiglobulin tests and rarely red cell haemolysis. Evogam® recipients should be 
monitored for clinical signs and symptoms of haemolysis. 
■  
Renal dysfunction 
 
There have been occasional reports of renal dysfunction and acute renal failure 
in patients receiving IVIg. In cases of renal impairment with Evogam® use, 
discontinuation should be considered.
■  
Thromboemblism 
 
Thrombotic events have been reported in association with human immunoglobulin 
therapy. Caution should be exercised in prescribing and administering Evogam® 
in patients with pre-existing risk factors for thrombotic events.
Adverse Reactions 
Local tolerability reactions of a mild to moderate intensity including infusion site pain, 
injection site haematoma or pruritis, erythema, local heat and/or induration are very 
commonly (≥1/10) reported at 8 to 12 hours after infusion. At 72 hours after infusion, 
the frequency of reported symptoms markedly decreases and the incidence of local 
reactions reduces with continued use of Evogam®. Other very commonly (≥ 1/10) 
reported reactions include headache, fever, nausea, diarrhoea and vomiting. Less 
common reactions include chills, back pain, arthralgia and hypotension.
Rarely, human immunoglobulin may cause allergic reactions and, in isolated cases, 
anaphylactic shock. Should an anaphylactic reaction to Evogam® develop, the infusion 
should be stopped and immediate treatment instituted with adrenaline and oxygen. 
Interactions with Other Medicines
Passively acquired antibody can interfere with the response to live attenuated virus 
vaccines such that vaccine administration should be deferred for at least 3 months. In 
the case of measles and varicella vaccines following normal immunoglobulin products, 
the impairment may persist for up to 12 months. Where deferral is impractical, patients 
Transfusion Medicine Handbook 3rd Edition 
Page 99

receiving such vaccines should have their antibody response checked. By the same 
token, immunoglobulins should not be administered for at least two weeks after 
live attenuated vaccines are given. Consultation with a NZBS Transfusion Medicine 
Specialist/Medical Officer is recommended.
5.5 
Other Products
5.5.1 Berinert® P (C1-esterase inhibitor)
Berinert® P does not have full New Zealand registration and so consultation with a NZBS 
Transfusion Medicine Specialist/Medical Officer is required prior to release of this product.
Berinert® P is a C1-esterase inhibitor concentrate supplied as 500 IU per vial (50 IU/
mL). Berinert® P is intended for slow intravenous injection or infusion.
Indications for Use 
Berinert® P is indicated for: 
■  
The management of patients with C1-esterase inhibitor deficiency and/or 
hereditary angioedema (HAE) 
Treatment should be initiated under the supervision of a physician experienced in the 
management of C1-esterase inhibitor deficiency.
The treatment of capillary leak syndrome with Berinert® P is not advised. 
Dosage and Administration
The recommended dose is 20 IU per kilogram body weight, rounded to the nearest 
500 IU. An additional dose may be required in less than 5% of patients with persistent 
or worsening clinical condition within a few hours of administration of the initial dose. 
It is recommended that Berinert® P be administered by slow intravenous injection 
4 mL/minute. 
5.5.2  Products from Australian Red Cross Blood Service (ARCBS)
From time to time there may be occasions when fractionated products prepared 
specifically from New Zealand plasma are unavailable or in short supply.
To ensure continuity of supply, NZBS may purchase supplementary stock of similar 
products from ARCBS. These products, manufactured by CSL Behring (using plasma 
from Australian donors) may be supplied in place of the equivalent New Zealand 
product. As they are unapproved medicines in New Zealand, a supply application is 
required under Section 29 of the Medicines Act 1981. 
Page 100 
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6
SPECIAL CIRCUMSTANCES 
6.1 
Management of Acute Blood Loss
Complications of major blood loss and massive transfusion associated with, for 
example, trauma, burns, surgery, obstetric haemorrhage and major gastrointestinal 
bleeding may jeopardise patients and challenge laboratory and blood transfusion 
resources. A successful outcome requires prompt action and good communication 
between clinical specialties, diagnostic laboratories, blood banks and NZBS.
Massive blood loss is usually defined as the loss of one blood volume within a 24 hour 
period (equivalent to 7% of ideal body weight in adults; 8 - 9% in children). Alternative 
definitions include the loss of 50% of blood volume within 3 hours and a rate of blood 
loss of 150 mL/minute. It is important that major blood loss is recognised early and 
appropriate action taken to prevent shock and its consequences.
The aim of treatment is the rapid and effective restoration of an adequate blood volume 
and to maintain blood composition within safe limits with regard to haemostasis, 
oxygen carrying capacity and biochemistry.
The essential features of management are:
■  
Restoring blood volume to maintain tissue perfusion and oxygenation.
■  
Achieving haemostasis by:
   

surgical control of bleeding. 
   

 correcting coagulopathy by expedient use of blood component therapy, 
based on results from early laboratory haemostasis screening.
The following table indicates likely crystalloid and blood transfusion requirements in 
response to acute blood loss, based on estimation of lost circulating volume.
Table 6.1: Transfusion Requirements in Response to Loss of Blood Volume
% Loss of Blood Volume
Action
15%  
No need for transfusion unless blood loss is 
(750 mL in an adult)
superimposed on pre-existing anaemia or when the 
patient is unable to compensate for this quantity of 
blood loss because of severe cardiac or respiratory 
disease.
15-30%  
Transfuse crystalloids. A requirement for red cell 
(800-1500 mL in an adult)
transfusion is unlikely unless the patient has a pre-
existing anaemia, reduced cardiopulmonary reserve 
or if blood loss continues.
30-40%  
Rapid volume replacement required with crystalloids. 
(1500-2000 mL in an adult)
Red cell transfusion will probably be required.
>40%  
Rapid volume replacement is required including red 
(>2000 mL in an adult)
cell transfusion.
Transfusion Medicine Handbook 3rd Edition 
Page 101

If bleeding continues after attempted surgical haemostasis and when the coagulation 
tests are abnormal or the platelet count reduced, then platelets, fresh frozen plasma, 
cryoprecipitate or a combination of these products may also be required.
In the setting of trauma-induced bleeding, early initiation of blood transfusion 
support with optimal ratios of plasma and platelets to red cell units may help achieve 
haemostasis and reduce the risk of exsanguination.
In trauma patients, use of the antifibrinolytic tranexamic acid is considered standard 
of care as an adjunct in arresting bleeding and should be administered as early as 
possible and within three hours of the trauma. The CRASH-2 trial included over 20,000 
trauma patients, at least 16 years old, with significant haemorrhage (or at risk of) who 
were within 8 hours of initial injury. Compared to placebo, administration of tranexamic 
acid 1g loading dose over 10 minutes followed by 1g infusion over 8 hours reduced 
hospital mortality and death due to haemorrhage within 4 weeks of injury. No increase 
in the rate of vascular occlusion (myocardial infarction, stroke, pulmonary embolism) 
was seen with the use of tranexamic acid. For further information on the use of this 
antifibrinolytic agent see Section 8.7: Tranexamic Acid
Clinical trials in humans have not demonstrated albumin solutions or other colloids 
to be superior to crystalloid in resuscitation, but larger quantities of crystalloid may 
be required. Synthetic colloids such as dextrans and hydroxyethyl starch should be 
avoided in patients at risk for acute kidney injury and otherwise limited to 1.5 litres 
per 24 hours in adults.
Aggressive volume resuscitation may cause problems with interstitial oedema, 
compartment syndrome, acute lung injury and, subsequent to haemodilution, 
exacerbations of anaemia, thrombocytopaenia and coagulopathy. A strategy of 
permissive hypotension, with minimal volume resuscitation and tolerating systolic 
blood pressures of 80-100 mmHg, is generally preferable while active bleeding is 
being controlled. Permissive hypotension is contraindicated in patients with traumatic 
brain injury and should be used with caution in the elderly. 
Large quantities of saline may cause hyperchloraemic metabolic acidosis with 
subsequent complications and this has increasingly led to the use of physiologically 
buffered fluids such as Plasmalyte 148 and compound sodium lactate (Hartmann’s 
or Ringer-Lactate).
Avoid saline in patients with severe liver disease for whom sodium overload is a risk. 
Specialist advice is recommended. For the same reason care should be taken with 
Albumex® 4 in these patients.
Table 6.2: Transfusion Support for Major Bleeding should be referred to in conjunction 
with a local massive transfusion protocol (MTP).
Page 102 
Transfusion Medicine Handbook 3rd Edition

esults 
esponsibility 
eat risk for a 
esults available 
esuscitation of trauma 
ed cell transfusion 
estimated 
elated adverse outcome
ed as soon as possible and within 3 
fected by colloid infusion 
e FBC and coagulation r
, befor
rong blood in tube (WBIT) poses gr
  Blood loss, including concealed blood loss, is 
often under
  Refer to local guidelines on r
patients and use of r
  Monitor CVP if haemodynamically unstable 
  A named senior person should take r
for communication and documentation
  Following trauma, tranexamic acid should be 
administer
hours
  Take samples at earliest opportunity as r
may be af
  W
transfusion-r
  May need to give FFP and platelets, as per local 
MTP
Comments 
 
 
 
 
 
 
 
 



■ 




>30 
e-warmed 
d blood volume 
, fibrinogen at least 
es 
ofile, arterial blood gas
, fibrinogen, Blood Bank 
ocedur
e peripheral cannulae 
opriate surgical team 
ect identity for transfusion samples 
opriate, tranexamic acid, as a 1g loading 
e corr
  Insert wide bor
  Give adequate volumes of pr
crystalloid +/- colloid
  Aim to maintain normal BP and urine output 
mL/hr in adults (or 0.5 mL/kg/hour) 
Most appr
Duty anaesthetist
Blood Bank
  Early surgical or obstetric intervention 
  Upper GI tract pr
  Interventional radiology
  If appr
dose over 10 minutes, followed by infusion of 1g 
over 8 hours
  FBC, PT/INR, APTT
sample, biochemical pr
  Ensur
  Repeat FBC, PT/INR, APTT
every 4 hours, or after one thir
replacement, or after FFP 
Intervention
 
 
 
  
  
  
 
 
 
 
 
 
 













, it may 
estrict volume 
diac injury
ransfusion Support for Major Bleeding 
culating volume 
e cir
opriate to r
est bleeding
Table 6.2: T
Activity
Restor
Note: in patients with major 
vessel or car
be appr
replacement after discussion with 
surgical team
Contact key personnel
Arr
Request laboratory 
investigations
Transfusion Medicine Handbook 3rd Edition 
Page 103



e using 

esults 
e laboratory 
elates with 
een befor
/L for multiple/9
, fibrinogen befor
ol corr
e laboratory r
oup and scr
≥ 100 x 10
 > 1.13 mmol/L2+
ovascular bleeding 
ovascular bleeding
e available, however take FBC sample 
> 1.5 x mean contr
fuse micr
eased micr
  Contact Blood Bank or on-call scientist 
  Collect sample for gr
emergency stock 
  Emergency use of RhD positive blood is 
acceptable if patient is male or post menopausal 
female
  Blood warmer indicated if large volumes ar
transfused rapidly
  Consider use of cell salvage
  Target platelet count 
central nervous system trauma or with sever
dif
  May need to transfuse platelets befor
results ar
first
  PT/APTT 
incr
  Take sample for PT/INR, APTT
FFP transfused
  May need to use FFP befor
available 
  Maintain ionised Ca
Comments 
 
 
 
 
 
 
 
 
 
 
 











ol
/L after 2 x 
/L 
9
ovided following 
9
e or 4 units for 
oup specific will be 
< 50 x 10
< 1.5 x mean contr
> 70 g/L 
oup known (15 to 45 
etransfusion testing
> 50 x 10
oximately 1 litr
eceipt of sample in laboratory) 
outine pr
eplacement 
oup O RhD negative 
om r
ossmatched ABO gr
ovided when blood gr
ossmatch compatible units pr
  Maintain haemoglobin 
  Blood needed immediately - use ‘emergency 
stock’ gr
  Blood needed in 15 to 45 minutes - 
uncr
pr
minutes fr
  Blood needed in 45 minutes or longer – 
cr
completion of r
  Maintain platelet count 
  Anticipate platelet count 
blood volume r
  Dose: 10 mL/kg for a neonate or small child, 
otherwise one adult therapeutic dose 
  Anticipate coagulation factor deficiency after 
blood loss of 1.5 x blood volume 
  Aim for PT/INR and APTT 
  Allow for 30 minutes thawing time 
  Dose: 12-15 mL/kg 
  (equivalent to appr
an average 70 kg adult) 
Intervention
 
 
 
 
 
 
 
 
 
 
 











 
ed cells 
ransfusion Support for Major Bleeding continued
Activity
Request suitable r
Consider the use of platelets
Consider the use of FFP
Table 6.2: T
Page 104 
Transfusion Medicine Handbook 3rd Edition


illebrand factor
eby complementing 
onectin ther
ecting multiple coagulation factor 
elated mortality is high
  Contains fibrinogen, FVIII, von W 
FXIII, and fibr
FFP in corr
deficiencies
  DIC-r
Comments 
 
 


> 2.0 
> 1.0 g/L
  Maintain fibrinogen 
  Allow for 30 minutes thawing time 
  Dose: 1 unit per 30 kg body weight in adults (or 
5 mL/kg paediatrics)
  In obstetric bleeding maintain fibrinogen 
g/L 
  Treat underlying cause (shock, hypothermia, 
acidosis) if possible
Intervention
 
 
 
 
 





ransfusion Support for Major Bleeding continued
ecipitate
Activity
Consider the use of 
cryopr
Suspect DIC
Table 6.2: T
Transfusion Medicine Handbook 3rd Edition 
Page 105

6.2 
Massive Transfusion Protocol (MTP) 
The MTP is a multidisciplinary process by which blood components are obtained 
rapidly for an exsanguinating patient. It is designed to provide clear guidance on the 
management of massive blood loss and facilitate communication between the clinical 
team and Blood Bank while streamlining the supply and administration of blood 
components to a patient during what may be a stressful situation. The clinical team 
is responsible for both activating the MTP and, when the crisis is over, inactivating 
the MTP. Activation of the MTP is really only indicated where the patient is bleeding 
so fast that goal-directed therapy is not practical. 
The MTP instructs Blood Bank staff to prepare in advance a designated set or “box” 
of blood components, provides confidence that those components will be available for 
immediate release when required, and guides the clinical team in their administration. 
After release of each box, Blood Bank will then prepare the next box but will not release 
it until cal ed for. The MTP also recommends additional components if certain thresholds 
are reached and the clinical team is responsible for requesting these. 
Because hospitals serve unique patient populations and Blood Banks have differing 
blood component stocks and ability to re-supply, the MTP for each DHB and affiliated 
Blood Bank is specific, having been developed in consultation with local clinicians 
responsible for managing these events. The principle however remains the same 
and that is to provide the best possible transfusion support and ensure a common 
understanding. 
Protocol Activation Criteria
The massive transfusion protocol may be activated for a specific patient when the 
following conditions are met:
■  
There is massive bleeding with either shock or abnormal coagulation
■  
The patient has been assessed as requiring the protocol by an experienced 
clinician
In the setting of massive blood loss the following steps should be followed to activate 
the massive transfusion protocol:
■  
The patient is assessed by an experienced clinician
■  
The patient is transfused 3 units of RBC or whole blood (either type-specific or 
emergency O RhD negative)
■  
The patient is reassessed and, if criteria are met, the MTP is activated
■  
The clinician (or delegate) must notify Blood Bank of the activation, informing 
them of the patient’s name, NHI and clinical area
■  
The Blood Bank staff prepare and issue Box One and thereafter the MTP flow 
chart is followed
■  
Each MTP box will be made ready for issue upon release of the preceding box 
but will only be issued upon request
Page 106 
Transfusion Medicine Handbook 3rd Edition


■  
To avoid delay in receiving the blood components an orderly or “designated 
runner” should be assigned
■  
Alongside regular clinical assessment of the patient, a full blood count, 
coagulation screen, ABG and serum calcium should be taken every 30 minutes
■  
Based upon laboratory results consider the use of specific blood components 
additional to those provided in standard MTP boxes
■  
Blood Bank must be informed when the patient is moved to another clinical 
department and/or the MTP is ceased.
Massive Transfusion Protocol Flowchart 
Below is an example of a typical MTP flowchart. It is however important to be familiar 
with the MTP used at your local DHB as there may be variations.
Transfusion Medicine Handbook 3rd Edition 
Page 107

The Australian National Blood Authority (NBA) Patient Blood Management Guidelines 
recommend early activation of the MTP and that fibrinogen is maintained > 2.0 g/L in 
obstetric patients. The role of permissive hypotension in these patients is uncertain as 
this may compromise fetal well-being and, in the postpartum period, uterine contraction.
6.3 
 Complications of Acute Blood Loss Associated with Large Volume 
Transfusions

When there is no pre-existing haemostatic problem, replacement of up to one blood 
volume (8-10 units of blood in an adult) using red cells and non-plasma fluids is unlikely 
to cause haemostatic problems due to dilution. Transfusion of much larger volumes 
may however lead to:
■  
Microvascular bleeding   
When major blood loss and massive transfusion is complicated by microvascular 
bleeding, with or without laboratory evidence of disseminated intravascular 
coagulation (DIC), the platelet count should be maintained > 50 x 109/L. With 
severe diffuse microvascular bleeding, a target platelet count ≥ 100 x 109/L is 
recommended.
 
To avoid dilutional coagulopathy use of non-blood products should be restricted 
until laboratory evidence that any haemostatic failure is corrected. Fresh frozen 
plasma is indicated if the microvascular bleeding is accompanied by prolonged 
PT/APTT > 1.5 times the mean control or the fibrinogen is < 1.0 g/L (< 1.5 g/L with 
laboratory evidence of disseminated intravascular coagulation). With persisting 
severe hypofibrinogenemia despite FFP, administration of cryoprecipitate is 
recommended.
 
While there is no evidence that the prophylactic transfusion of fresh frozen plasma 
or platelets to patients receiving large volume transfusions reduces the risk of 
microvascular bleeding, these blood components are included emperically in 
massive transfusion protocols in an attempt to maintain the platelet count > 50 
x 109/L and PT/APTT < 1.5 times the mean control. 
■  
Hypocalcaemia 
 
The citrate anticoagulant in some blood components (i.e., fresh frozen plasma) 
binds ionised calcium. It should be noted that red cells in additive solution 
contain only traces of citrate.
 
Usually the rapid metabolism of citrate by the liver prevents lowering of plasma 
ionised calcium. In neonates and patients who are hypothermic, the combined 
effects of hypocalcaemia and hyperkalaemia may be cardiotoxic. If there is ECG 
or clinical evidence of hypocalcaemia, 5 mL of 10% calcium gluconate (for an 
adult) should be given intravenously. If necessary the dose should be repeated 
until the ECG is normal. 
■  
Hyperkalaemia 
 
The plasma or additive solution in a unit of red cells or whole blood stored for 
four to five weeks may contain 5-10 mmol of potassium. In the presence of 
acidaemia and hypothermia this additional potassium load can lead to cardiac 
arrest. Keeping the patient warm best prevents this problem.
■  
Hypothermia   
The rapid transfusion of blood at 4°C can lower the body’s core temperature by 
several degrees. Keeping the patient warm is the best safeguard to prevent this 
Page 108 
Transfusion Medicine Handbook 3rd Edition

problem. A blood warmer should be used in adults receiving large volumes of 
blood transfused at rates above 50 mL/kg/hour (in children above 15 mL/kg/hour). 
 
It should be noted that hypothermic patients with a core body temperature < 35°C 
may be functionally coagulopathic even though coagulation tests performed in 
the laboratory at 37°C may be normal.
■  
Acid-base disturbances   
Despite the lactic acid content in transfused blood (1-2 mmol/unit), fluid 
resuscitation usually improves acidosis in a shocked patient. In practice, 
transfused citrate can contribute to metabolic alkalosis when large volumes of 
plasma components are transfused. 
■  
Adult respiratory distress syndrome 
 
The risk is minimised if tissue oxygenation is optimised by good perfusion and 
over transfusion is avoided. The use of albumin solutions to maintain plasma 
oncotic pressure is often stated to be important but controlled studies have not 
proven any advantage of albumin solution over crystalloid fluids for resuscitation. 
It should be noted that trauma (which may be the cause of major blood loss) is also 
known to cause or contribute to hypothermia, acidosis and coagulopathy, and therefore 
may lead to the problems described in association with massive transfusion.
6.4 
 Avoidable Haemostatic Problems in Elective Surgery
Any patient for whom elective surgery is planned must be asked about previous 
episodes of abnormal bleeding. Underlying medical conditions, the taking of medication 
that may be associated with impaired haemostatic function, or abnormal laboratory 
haemostasis test results may require the postponement of elective surgery until the 
abnormality has been identified or confirmed. Appropriate procedures including 
consultation with specialists in haematology, anaesthesiology and cardiology should 
be undertaken prior to surgery to minimise the perioperative risks for bleeding and, in 
the case of anticoagulant or antiplatelet withdrawal, thromboembolism.
Congenital abnormalities of haemostasis such as haemophilia should be managed in 
consultation with a specialist haemophilia centre. 
6.4.1   Warfarin
Unless contraindicated, warfarin anticoagulation should be stopped early enough 
before elective surgery to allow the prothrombin time (or INR; International Normalised 
Ratio) to approach normal. This should be guided by a local protocol for preoperative 
anticoagulant management, taking into account patient-related risk factors for both 
thrombosis and bleeding. Bridging anticoagulation with either low molecular weight 
heparin or heparin infusion may be indicated for patients with at least a moderate risk 
of thrombosis. Prior to surgery where the INR is stable and therapeutic, withdrawal of 
warfarin for 3 - 5 days is generally adequate to achieve reversal sufficient for surgery. 
A longer period may be required in the presence of malnutrition or other factors 
predisposing to vitamin K deficiency. The Australasian Society of Thrombosis and 
Haemostasis (ASTH) has updated and published Consensus Guidelines for Warfarin 
Reversal in The Medical Journal of Australia 2013; 198 (4): 198-199. The Guidelines 
contain recommendations for the management of patients on long-term warfarin 
undergoing invasive procedures. Additionally, the NZBS Reversing Warfarin app 
developed by Health Obs Ltd, available for android and iPhone, provides guidance 
for managing patients undergoing elective and emergency surgery.
Transfusion Medicine Handbook 3rd Edition 
Page 109

6.4.2  Non-Vitamin K-Dependent Oral Anticoagulants (NOAC)
The non-vitamin K-dependent oral anticoagulants, direct inhibitors of thrombin such 
as dabigatran (Pradaxa) or factor Xa such as rivaroxaban (Xarelto) and apixiban 
(Eliquis), should be stopped early enough before elective surgery to allow reversal of 
the anticoagulant effect. This should be guided by a local protocol for preoperative 
anticoagulant management with, in the case of dabigatran, particular attention paid 
to the patient’s renal function and hence elimination of the drug. The Australasian 
Society of Thrombosis and Haemostasis has published New Oral Anticoagulants: 
A Practical Guide on Prescription, Laboratory Testing and Peri-procedural/Bleeding 
Management
 in The Internal Medicine Journal 2014; 44: 525-536. The Guide contains 
recommendations for the management of patients taking NOAC undergoing invasive 
procedures. Similarly, the Pharmaceutical Management Agency of the New Zealand 
Government (PHARMAC), has produced a concise document, Guidelines for Testing 
and Perioperative Management of Dabigatran
 (www.pharmac.govt.nz). Additionally, 
the Rivaroxaban app and the Dabigatran app developed by Health Obs Ltd, available 
for android and iPhone, provide guidance for managing patients undergoing elective 
and emergency surgery.
Table 6.3: Pharmacologic Properties of Non-Vitamin K-Dependent Oral Anticoagulants 
Dabigatran
Rivaroxaban
Apixaban
Peak level
2 hours
1.5 - 4 hours
3 - 4 hours
Renal clearance
80%
66%
27%
11 - 17 hours
5 - 9 hours
8 - 15 hours
Half-life 
(longer in elderly and, especially dabigatran, with impaired renal function)
Table 6.4:  Suggested Approach for the Withdrawal of Non-Vitamin K-Dependent Oral 
Anticoagulants Prior to Elective Surgery
Dabigatran
Rivaroxaban
Apixaban
Normal or mild renal 
impairment
1  
2 days
2 days
2 days
(eGFR > 50 mL/min)
Moderate renal 
impairment
1  
4 days
3 days
3 days
(eGFR 30 - 50 mL/min)
Severe renal impairment
5 days
4 days
3 days
(eGFR < 30 mL/min)
1 For surgery with minimal bleeding risk, NOAC withdrawal may be shortened by 1 day. For surgery with 
high bleeding risk, NOAC withdrawal should be prolonged by 1 day.
2 NOAC use is contraindicated or generally not recommended in the setting of severe renal impairment and 
should not be restarted post-operatively.
Page 110 
Transfusion Medicine Handbook 3rd Edition

6.4.3 Aspirin
The antiplatelet effect of aspirin is mediated via irreversible acetylation of platelet 
cyclo-oxygenase, specifically COX-1, and the resulting inhibition of thromboxane A2 
synthesis. Aspirin is indicated for the management of ischaemic atherosclerotic vascular 
disease including coronary artery and cerebrovascular disease and is used primarily 
in secondary prevention. Aspirin is used in combination with ADP-receptor inhibitors 
for the management of acute coronary syndromes (ACS) and for thromboprophylaxis 
following stent implantation. It may also be used for the management of some 
rheumatological disorders. While a single 75 mg dose of aspirin may impair platelet 
function for several days, the effect is less than with newer antiplatelet agents and 
most surgery can be performed after discontinuing aspirin at most the day prior to 
surgery. Prior to neurosurgery, transurethral prostatectomy or other invasive procedures 
with a major risk of bleeding or complications from bleeding, aspirin should (unless 
contraindicated) be stopped 3 days before planned surgery. If aspirin-induced platelet 
defect contributes to abnormal bleeding, desmopressin and tranexamic acid are likely 
to be effective in controlling haemostasis. Refer to Section 8.6: Desmopressin and 
Section 8.7: Tranexamic Acid for further information on these agents including dosing 
guidelines. Platelet transfusion is seldom necessary.
6.4.4  Non-steroidal Anti-inflammatory Drugs (NSAID)
Non-steroidal anti-inflammatory drugs cause reversible, but non-selective, inhibition 
of cyclo-oxygenase, both COX-1 and COX-2. The effects usually last for hours, 
as opposed to lasting days with aspirin. Normal platelet function is usually rapidly 
restored once the NSAID is stopped. The length of time that these medications 
should be stopped prior to an invasive procedure varies as the antiplatelet effect is 
dependent on the half-life of the NSAID being used. If NSAID-induced platelet defect 
contributes to abnormal bleeding, desmopressin and tranexamic acid may be effective 
in controlling haemostasis. Platelet transfusion is seldom necessary. The effect of both 
desmopression and platelet transfusion will be reduced in the presence of active drug.
6.4.5 P2Y  Adenosine Diphosphate (ADP) Receptor Inhibitors
12
Clopidogrel and the other thienopyridines, ticlopidine (not commonly in use) and 
prasugrel (Effient), irreversibly inhibit the P2Y  subtype of ADP receptor on platelet 
12
cell membranes. Ticagrelor (Brilinta), a cyclopentyltriazolopyrimidine reversibly inhibits 
the P2Y  ADP receptor. Clopidogrel is indicated for the management of ischaemic 
12
atherosclerotic vascular disease including coronary artery and cerebrovascular disease. 
The newer agents prasugrel and ticagrelor are indicated for the management of acute 
coronary syndromes (ACS) and as prophylaxis against stent thrombosis, usually in 
combination with aspirin. In some situations triple therapy in combination with an 
anticoagulant is indicated. P2Y  ADP receptor inhibitors should be used with caution 
12
in patients at increased risk of bleeding such as in the setting of trauma, surgery or 
other pathological conditions of haemostasis. Unless contraindicated, clopidogrel 
should be discontinued at least 5 days prior to surgery where an antiplatelet effect 
is undesirable. Prasugrel should be discontinued 7 days prior to surgery. Ticagrelor, 
although reversible, has a pronounced effect on platelet function and should be 
discontinued at least 3 days prior to semi-urgent surgery and 5 days prior to elective 
surgery. If P2Y  ADP receptor-induced platelet defect contributes to abnormal 
12
Transfusion Medicine Handbook 3rd Edition 
Page 111

bleeding, tranexamic acid together with a 1 - 2 unit platelet transfusion is likely to be 
effective in controlling haemostasis. Ticagrelor has a long half-life and inhibition of 
even transfused platelets may occur. An effect on transfused platelets may be seen 
for up to 6 hours following a loading dose of prasugrel. In patients with ACS who 
have recently received a coronary stent, platelet transfusion carries a risk of arterial 
and stent thrombosis and should therefore be restricted to situations involving serious 
bleeding or high bleeding risk.
6.4.6  Platelet Glycoprotein IIb (GPIIb) and IIIa (GPIIIa) Inhibitors  
The platelet glycoproteins GPIIb and GPIIIa have important roles in normal haemostasis 
and pathological thrombosis. The peptides tirofiban (Aggrastat) and eptifibatide 
(Integrilin) and the monoclonal antibody abciximab (ReoPro) inhibit GPIIb and GPIIIa 
receptors. Inhibition of platelet aggregation occurs through blocking the final common 
pathway, the cross-bridging of platelets, following binding of fibrinogen to the activated 
GPIIb/IIIa receptor. These agents are indicated, in combination with aspirin and heparin 
anticoagulation, for the management of acute coronary syndromes (ACS) managed 
medically with or without percutaneous coronary intervention (PCI). Current applicability 
is however limited following the introduction of routine dual antiplatelet therapy using 
P2Y12 ADP receptor blockers and percutaneous coronary stenting. Tirofiban and 
eptifibatide bind reversibly to GPIIb/IIIa receptors and the antiplatelet effect, in the 
absence of moderate renal impairment, recovers within 4 - 8 hours following cessation 
of treatment. In contrast, platelet binding by abciximab is irreversible and recovery of 
platelet function is delayed for 24 - 48 hours. By reducing thrombin burst generation, 
abciximab also inhibits normal coagulation and major bleeding may be observed 
within 12 hours of therapy, particularly following cardiac surgery. The antiplatelet 
effects of abciximab can be reversed by platelet transfusion. A small percentage of 
patients (≤ 1%) may experience acute severe thrombocytopenia following treatment 
with GPIIb/GPIIIa inhibitors.
Table 6.5: Pharmacologic Properties of Antiplatelet Agents
Aspirin
Clopidogrel
Prasugrel
Ticagrelor
Mode of action
Prodrug
Prodrug
Prodrug
Direct acting
Active drug t1/2
 2 - 4 hours
30 mins
7 hours1
7 - 9 hours
Prodrug t1/2
NA2
6-8 hours
NA2
NA
Inhibition type
Irreversible3
Irreversible3
Irreversible3
Reversible4
Grade of effect
Mild
Moderate
Strong
Strong
Specific antidote
No
No
No
No
1 Range 2 - 15 hours.
2 Aspirin and prasugrel are rapidly converted to an active metabolite.
3 The duration of inhibition is for the life span of the plalelet, i.e., 7-10 days. However, the effect on platelet-

mediated haemostatic function declines more rapidly as approximately 10-15% of the circulating platelet 
pool is replaced daily.

4 The duration of inhibition is dependent on the half-life (t ). In general, it can be expected that after two 
1/2
half-lives the effect of ticagrelor has reduced to 25%. After four to five half-lives the remaining effect of 
ticagrelor is 
<5%.
Page 112 
Transfusion Medicine Handbook 3rd Edition

Table 6.6: Managing Bleeding in Patients on Antiplatelet Agents
Aspirin
Clopidogrel
Prasugrel
Ticagrelor
Withdrawal  
pre-surgery

0 - 1 day1
5 days
7 days
5 days
Bleeding reversal2
Tranexamic acid
Yes
Yes
Yes
Yes
Desmopressin
Yes
Possible effect
No effect
No effect
Platelets3
Seldom required
1 unit
2 units
2 units
1 Prior to neurosurgery, transurethral prostatectomy or other invasive procedures with a major risk of 
bleeding or complications from bleeding, aspirin should (unless contraindicated) be stopped for 3 days. 
2 Where appropriate, local haemostatic measures should be used including mechanical compression, 
topical application of tranexamic acid and surgical/radiological intervention to identify sources of bleeding. 
3 Repeated doses may be required to achieve or maintain effect. 
6.5 
Oral Anticoagulant Induced Bleeding or Overdose
6.5.1 Warfarin
Withholding warfarin along with the judicious use of oral vitamin K1 are the management 
options of choice unless rapid reversal of anticoagulation is required. Although 
intravenous administration of vitamin K1 produces a more rapid response (onset 
within 6 - 8 hours), at 24 hours both routes achieve a similar correction of INR. The 
intravenous route may rarely be associated with anaphylaxis. The full effect of vitamin 
K1 in reducing the INR takes up to 24 hours even when given in large doses. For 
immediate reversal of clinically significant bleeding, treatment with Prothrombinex®-VF 
covers the period until vitamin K1 achieves full effect. Subsequent doses of vitamin 
K1 may be necessary for maintaining correction of the INR achieved by coagulation 
factor replacement. Prothrombinex®-VF is a human prothrombin complex concentrate 
(PCC) containing factors II, IX and X together with only low levels of factor VII. The 
use of fresh frozen plasma should therefore be considered as a source of factor VII in 
life-threatening or critical organ bleeding. If no PCC is available, fresh frozen plasma 
should be transfused however this is less effective. The FFP dose for an adult in this 
setting is 15 mL/kg.
The ASTH has updated and published Consensus Guidelines for Warfarin Reversal 
in The Medical Journal of Australia, Med J Aust 2013; 198 (4): 198-199, from which 
the following table is adapted.
Transfusion Medicine Handbook 3rd Edition 
Page 113

Table 6.7: Managing Overdose or Bleeding in Patients on Warfarin Therapy
Clinical setting
Action
INR greater than the 
■ 
 Reduce or omit next dose of warfarin and resume 
therapeutic range 
therapy at a lower dose when INR approaches 
but less than 4.5; no 
therapeutic range
bleeding
■ 
 If INR is only minimally above the therapeutic range (up 
to 10%) dose reduction may not be necessary
INR greater than 4.5 
■ 
 Stop warfarin and consider reasons for elevated INR 
but less than 10.0; no 
■ 
 If bleeding risk is high1, give vitamin K1 1.0-2.0 mg 
bleeding 
orally or 0.5-1.0 mg intravenously
■ 
 Measure the INR within 24 hours (vitamin K1 effect on 
INR expected within 6-12 hours) and monitor closely 
for 1 week
■ 
 Restart warfarin at a reduced dose once the INR 
approaches therapeutic range
INR greater than 10.0; 
■ 
 Stop warfarin
no bleeding2
■ 
 Give 3.0-5.0 mg vitamin K1 orally or intravenously
■ 
 If bleeding risk is high1, consider Prothrombinex®-VF 
15-30 IU/kg
■ 
 Measure the INR within 24 hours (vitamin K1 effect on 
INR expected within 6-12 hours) and monitor closely 
for 1 week
■ 
 Restart warfarin at a reduced dose once the INR 
approaches therapeutic range
Life-threatening3 or 
■ 
 Stop warfarin
critical organ bleeding  ■   Give 5.0-10.0 mg IV vitamin K1, and Prothrombinex®-
with an INR ≥ 1.5
VF 50 IU/kg4 and fresh frozen plasma 150-300 mL
■ 
 If Prothrombinex®-VF is unavailable, administer fresh 
frozen plasma 15 mL/kg
■ 
 Assess patient continuously until INR is reversed and 
bleeding stops
Clinically significant 
■ 
 Stop warfarin
(non-life-threatening) 
■ 
 Give 5.0-10.0 mg IV vitamin K1, and Prothrombinex®-
bleeding with an INR 
VF 35-50 IU/kg
≥ 2.0
■ 
 If Prothrombinex®-VF is unavailable, administer fresh 
frozen plasma 15 mL/kg
■ 
 Assess patient continuously until INR is reversed and 
bleeding stops
Minor bleeding with 
■ 
 Omit warfarin and repeat INR the following day
any INR < 10.0 
■ 
 Adjust warfarin dose to maintain INR in therapeutic 
range
■ 
 If bleeding risk is high1 or INR > 4.5, consider vitamin 
K1 1.0-2.0 mg orally or 0.5-1.0 mg intravenously
Page 114 
Transfusion Medicine Handbook 3rd Edition

1 Risk factors for major bleeding include recent major bleed within previous four weeks, major surgery within 
previous two weeks, platelet count < 50 x 109/L, known liver disease, concurrent antiplatelet therapy.
2 New Zealand laboratories generally report INR values up to 8.0. Above this, results are reported as INR > 8.0.
3 Includes intracranial bleeding.
4 Consider a Prothrombinex®-VF dose less than 50 IU/kg when INR is 1.5-1.9.

The NZBS Reversing Warfarin app developed by Health Obs Ltd, available for android 
and iPhone, also provides guidance for managing patients with bleeding.
6.5.2   Non-Vitamin K-Dependent Oral Anticoagulants (NOAC) 
There is limited clinical data on reversal of the direct thrombin inhibitor dabigatran 
and the factor Xa inhibitors rivaroxaban and apixaban. As there is no specific reversal 
agent available, the mainstay of current management for drug-related bleeding is 
withholding NOAC together with best supportive care for local control of bleeding and 
maintenance of haemodynamic stability. The anticoagulant effect will not be reversed 
by the administration of vitamin K or infusion of plasma. Idarucizumab, a specific 
intravenous reversal agent for dabigatran, is showing promising early results in clinical 
trials. The antibody fragment completely reverses within minutes the anticoagulant 
effect of dabigatran.
The ASTH has published New Oral Anticoagulants: A Practical Guide on Prescription, 
Laboratory Testing and Peri-procedural/Bleeding Management
 in The Internal Medicine 
Journal 2014; 44: 525-536. The Guide contains recommendations for the management 
of patients taking NOAC with bleeding complications. Similarly, PHARMAC, has 
produced a concise document, Guidelines for Management of Bleeding with 
Dabigatran
 (www.pharmac.govt.nz). The recommendations may change as new 
evidence becomes available. Additionally, the Rivaroxaban app and the Dabigatran 
app developed by Health Obs Ltd, available for android and iPhone, provide guidance 
for managing patients with bleeding.
Table 6.8:  Managing Bleeding in Patients on Non-Vitamin K-Dependent Oral Anticoagulant 
Therapy
Clinical setting
Action
General measures for 
■ 
 Initiate standard resuscitation procedures as required
any patient bleeding 
■ 
 Take samples for FBC, creatinine, group and screen, 
on NOAC therapy
routine coagulation studies
■ 
 Dabigatran - APTT, thrombin time; consider dabigitran 
level using a dilute thrombin clotting time (Hemoclot) 
assay
■ 
 Rivaroxaban - PT1, drug specific anti-Xa level
■ 
 Apixaban - drug specific anti-Xa level (if available)
Minor bleeding
■ 
 Local haemostatic measures
 
-  mechanical compression
 
-  topical tranexamic acid
■ 
 Delay next dose of NOAC
■ 
 Consider appropriateness of continuing therapy in 
consultation with prescribing physician
Transfusion Medicine Handbook 3rd Edition 
Page 115

Table 6.8:  Managing Bleeding in Patients on Non-Vitamin K-Dependent Oral Anticoagulant 
Therapy continued
Clinical setting
Action
Clinically significant2 
■ 
 Stop NOAC
(non-life-threatening) 
■ 
 Administer oral charcoal if NOAC ingestion < 2 h prior
bleeding 
■ 
 Local haemostatic measures
 
-  mechanical compression
 
-  surgical/radiological intervention to identify and  
 
-  treat source of bleeding
■ 
 Maintain hydration to aid drug clearance
■ 
 Transfusion support
 
-  RBC as indicated by haemoglobin 
 
-  PLT if < 50 x 109/L or antiplatelet therapy
 
-   FFP only if concerned about dilutional coagulopathy
■ 
 Consider use of tranexamic acid 15-30 mg/kg IV +/- 
infusion for mucosal bleeding
Life-threatening 
■ 
 Stop NOAC
or critical organ 
■ 
 Administer oral charcoal if NOAC ingestion < 2 h prior
bleeding3 
■ 
 Local haemostatic measures
 
-  mechanical compression
 
-   surgical/radiological intervention to identify and 
treat source of bleeding
■ 
 Maintain hydration to aid drug clearance
■ 
 Transfusion support
 
-  RBC as indicated by haemoglobin 
 
-  PLT if < 100 x 109/L or antiplatelet therapy
 
-   FFP only if concerned about dilutional 
coagulopathy
■ 
 Consider use of the following pro-haemostatic agents4
 
-   Tranexamic acid 15-30 mg/kg IV +/- infusion for 
mucosal bleeding
  - Prothrombinex®-VF 25-50 IU/kg
 
-  FEIBA 50 IU/kg
■ 
 Consider dialysis for dabigatran-related bleeding5
■ 
 Assess patient continuously until bleeding stops
1 Using a thromboplastin sensitive to rivaroxaban.
2 Clinically significant bleeding - reduction in Hb 
 20 g/L, transfusion of  2 units of RBC.
3 Life-threatening bleeding with hypotension not responding to resuscitation or bleeding in critical area or 
organ (intraocular, intracranial, intraspinal, compartment syndrome, retroperitoneal or pericardial).
4 This is an off-license use of Prothrombinex®-VF and FEIBA and the risk of thrombotic complications with 
these agents when used for this indication is unclear. Their use is supported by laboratory data and clinical 
evidence in animals but clinical evidence in humans supporting an improvement in clinical outcomes is lacking.

5 Dialysis is indicated if dabigatran level is high as indicated by excessively prolonged APTT > 80 sec or 
dabigatran level > 500 ng/mL and/or impaired renal function. Four hours of dialysis will reduce drug level 
by approximately 60%.
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6.6  
Thrombolytic Therapy
Although bleeding is not a common complication of fibrinolytic therapy at normal 
doses, the risk is not predicted by laboratory monitoring. If there is serious bleeding, 
fresh frozen plasma and cryoprecipitate will raise a low fibrinogen level. 
An anti-fibrinolytic agent such as tranexamic acid should only be used if life-threatening 
bleeding is encountered. As large clots may form at the site of bleeding, these agents 
are contraindicated in renal tract bleeding. It should however be noted that the use of 
anti-fibrinolytic agents is not contraindicated in the presence of intracranial bleeding 
following thrombolysis.
6.7  
Disseminated Intravascular Coagulation (DIC)
In this syndrome there is generation of thrombin leading to consumption of circulating 
coagulation factors and platelets with subsequent fibrin deposition. Ischaemic 
organ damage particularly in the renal circulation can occur due to microthrombi. 
The treatment of DIC involves supportive care while treating the underlying primary 
condition. In the presence of active bleeding, or where there is a high risk of major 
bleeding such as prior to some invasive procedures, transfusion support to replace 
coagulation factors and platelets is likely to be appropriate. If the patient is bleeding 
and there are no problems with volume replacement, fresh frozen plasma is optimal 
as it contains a full spectrum of coagulation factors. Where real concern exists 
for intravascular fluid overload, Prothrombinex®-VF may be considered, as the 
reconstituted volume for infusion is smaller. Correction of the coagulation defect is 
however only likely to be partial and Prothrombinex®-VF is generally contraindicated in 
the presence of DIC. For bleeding patients with severe hypofibrinogenaemia despite 
FFP replacement, cryoprecipitate should be infused keeping the fibrinogen level > 1.5 
g/L. Antithrombin concentrates may be considered where DIC is secondary to sepsis 
or in cases of thrombosis-predominant DIC treated with therapeutic dose heparin. A 
platelet count of 10 - 20 x 109/L can usually be tolerated in the absence of bleeding 
while transfusion is recommended with a platelet count < 50 x 109/L in the presence 
of active bleeding or prior to invasive procedures. Where the procedure is neuraxial a 
higher platelet is likely to be desirable.
The management of DIC requires careful coordination between the treating clinician 
and NZBS to ensure adequate supplies of blood components and plasma products 
are available and that these are used based upon relevant coagulation tests.
6.8  
Cardiopulmonary Bypass
Cardiopulmonary bypass usually impairs haemostatic mechanisms and, as a result, 
bleeding complications may be severe. The effect is especially pronounced for patients 
who have been on prolonged bypass for more than 2 hours, in ‘redo’ operations or 
with surgery for infective endocarditis. A number of mechanisms are involved including 
haemodilution, effects on platelet function, reduced levels of coagulation factors, 
intraoperative heparin anticoagulation, induced hypothermia, acidosis, hyperfibrinolysis 
and preoperative anticoagulation or antiplatelet therapy. 
Routine laboratory tests of coagulation do not accurately predict the full nature and 
clinical importance of the haemostatic defect. Intra-operative point-of-care testing with 
an activated clotting time (ACT) assay, together with viscoelastic global assessments 
Transfusion Medicine Handbook 3rd Edition 
Page 117

of coagulation using whole blood thromboelastography (TEG) or thromboelastometry 
(TEM), is increasingly being used alongside PT/APTT and fibrinogen results. 
Platelet transfusion is indicated if, despite heparin reversal with protamine sulphate, 
there is diffuse microvascular bleeding with platelets < 100 x 109/L or suspected 
platelet dysfunction. In the presence of non-surgical bleeding, fresh frozen plasma and 
cryoprecipitate may help to correct prolonged clotting times, improve haemostasis and 
reduce transfusion requirements. The routine use of fresh frozen plasma, cryoprecipitate 
or platelets at the end of bypass does however not reduce transfusion requirements. 
Aprotinin (Trasylol®) is no longer available due to concerns regarding effect on renal 
function. Tranexamic acid is commonly used as an antifibrinolytic and has been shown 
to reduce red cell transfusion requirement.
Red cell components for patients undergoing cardiac bypass surgery   
Literature review provides no evidence supporting the use of fresh blood for cardiac 
bypass surgery. Accordingly, NZBS policy on the provision of red cell components, 
including whole blood, for use in recipients undergoing cardiopulmonary bypass 
surgery is as follows:
■  
Adult Cardiac Bypass Surgery 
 
Resuspended red cells less than 14 days old will normally be made available for 
adult patients as a replacement for blood loss. Resuspended red cells less than 
10 days old will normally be made available for patients with renal impairment. 
It is the responsibility of the treating clinician to indicate this requirement to the 
Blood Bank.
■  
Paediatric Cardiac Bypass Surgery 
 
Resuspended red cells less than 5 days old will normally be made available for 
paediatric patients as a replacement for blood loss. Where possible, whole blood 
less than 2 days old will be provided for the purpose of bypass circuit priming. 
6.9  
Haemolytic Disease of the Fetus and Newborn (HDFN)
HDFN occurs when maternal IgG antibodies (most commonly anti-D) travel across the 
placenta and bind to fetal red cells having the corresponding antigen. The affected fetal 
red cells may be destroyed by the fetal reticuloendothelial system causing extravascular 
haemolysis and fetal anaemia. 
The antibodies that cause HDFN are produced either as a consequence of earlier 
pregnancies (when fetal red cells with paternally derived antigens that the mother lacks, 
enter the maternal circulation during pregnancy) or because of a previous transfusion. 
In the most severe cases of HDFN the fetus may die in utero or be born with severe 
anaemia that requires exchange transfusion. There may also be severe neurological 
damage (kernicterus) as a result of a high bilirubin level. 
Anti-D, an antibody to the RhD antigen, is the most important cause of HDFN. Clinically 
significant IgG antibodies against other blood group antigens can also be responsible 
for causing HDFN for example anti-c, -K, -E, -Fya. These antibodies occur in about 
0.5% of pregnancies and may occasionally cause severe haemolysis. Although ABO 
incompatibility between mother and fetus is common, severe HDFN due to IgG anti-A 
and anti-B antibodies is very rare in New Zealand.
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10
Screening in Pregnancy 
All pregnant women should have the following antenatal testing performed:
■  
ABO and RhD group following booking for antenatal care at 12 - 16 weeks. 
This identifies RhD negative mothers. 
■  
Red cell antibody screen to test for antibodies that may cause HDFN. If 
an antibody is detected at booking, it should be monitored throughout the 
pregnancy in case the level of antibody increases.
■  
If a significant maternal antibody is found it may be useful to test the father’s 
red cells to see if they carry the antigen against which the antibody is directed. 
If homozygous for the antigen concerned, the fetus will also be positive. If 
heterozygous, there is a 50% chance that the fetus will be positive. 
Further information can be found in the ANZSBT/RANZCOG Guidelines for Blood 
Grouping & Antibody Screening in the Antenatal and Perinatal Setting
 (2007) upon 
which the following table is based.
Table 6.9: Timetable for Routine Antenatal Blood Group and Antibody Screen 
Testing Requirements
Testing Interval / Comments 
Blood Group - ABO and RhD 
All pregnancies
■ 
 Initial visit and for pretransfusion testing
Antibody Screening
All pregnancies
■ 
 Initial visit and for pretransfusion testing
RhD negative females
■ 
 For those RhD negative females who will receive 
anti-D immunoglobulin (at 28 weeks or at the 
time of any sensitising event), the blood sample 
must be collected prior to its administration
Antibody Identification
All pregnancies
■ 
 At initial antibody detection
Antibody Titration / Quantitation
Rh antibodies and other 
■ 
 In the event that clinically significant antibodies 
potentially clinically significant 
are detected, further testing is indicated at 
antibodies capable of causing 
intervals no greater than 4 weeks
HDFN
■ 
 Seek specialist advice
Management of HDFN
It is important that women with potentially severe HDFN are referred without delay 
to a specialist obstetric unit. The referral should be made prior to 20 weeks in those 
patients who have had a previously affected baby. Management of an affected fetus 
may include intrauterine transfusion, early delivery, phototherapy and exchange 
transfusion. 
Transfusion Medicine Handbook 3rd Edition 
Page 119

Prevention of HDFN Due to Anti-D 
The minimum volume of RhD positive red cells that will immunise a RhD negative 
woman is of the order of 0.1 - 0.25 mL. Clinical studies indicate that the administration 
of anti-D immunoglobulin to a RhD negative mother within 72 hours of the birth of a 
RhD positive infant reduces the incidence of Rh isoimmunisation from 12 - 13% to 
1 - 2%. A small number (1.5 - 1.8%) of RhD negative mothers are immunised by their 
RhD positive fetus despite postpartum administration of anti-D immunoglobulin. Studies 
have also shown that this number can be reduced to < 1.0% by routine antenatal 
prophylaxis with anti-D immunoglobulin at 28 and 34 weeks of pregnancy. Although 
definitive studies have not been performed, guidelines promote the use of anti-D 
immunoglobulin for other potential y sensitising obstetric events in which fetomaternal 
haemorrhage is known to occur. 
Anti-D immunoglobulin should not be given to RhD negative women with detectable 
anti-D except where the antibody is passively acquired due to prior antenatal 
administration. If unsure whether the anti-D detected in the mother’s blood is passively 
acquired or preformed, the treating clinician and/or a NZBS Transfusion Medicine 
Specialist should be consulted. If there is continuing doubt, anti-D immunoglobulin 
should be administered. Although there is no benefit in administering anti-D 
immunoglobulin to a woman who is already sensitised to RhD antigen, there is no 
more risk than when it is given to a woman who is not sensitised.
The following table is based on the 2003 Australian NBA Guidelines on the Prophylactic 
Use of RhD Immunoglobulin (Anti-D) in Obstetrics
 and the 2013 BCSH Guideline for the 
Use of Anti-D Immunoglobulin for the Prevention of HDFN.
 In 2011 the Royal Australian 
and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) endorsed 
the 2003 NBA Guidelines, however it should be noted that the NZ Ministry of Health 
does not recommend routine antenatal anti-D prophylaxis (RAADP).
Table 6.10:  Indications for Use of Anti-D Immunoglobulin for the Prevention of HDFN 
(unless the fetus is confirmed to be RhD negative)
Timing
Clinical Indication 
Routine antenatal 
A RhD negative woman, not previously immunised 
prophylaxis1
to produce anti-D; one dose at each of 28 and 34 
weeks gestation.2 
Anti-D immunoglobulin dose: 625 IU (125 µg)
Potentially sensitising event 
A RhD negative woman, not previously immunised 
during first trimester up 
to produce anti-D, with an obstetric indication.
to and including 12 weeks 
■ 
 Uterine bleeding where this is repeated, heavy 
gestation
or associated with abdominal pain3
■ 
 Miscarriage3
■ 
 Termination of pregnancy
■ 
 Ectopic pregnancy
■ 
 Molar pregnancy
Anti-D immunoglobulin dose: 250 IU (50 µg)4
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Table 6.10:  Indications for Use of Anti-D Immunoglobulin for the Prevention of HDFN 
(unless the fetus is confirmed to be RhD negative) continued
Timing
Clinical Indication 
Potentially sensitising event 
A RhD negative woman, not previously immunised 
beyond first trimester5
to produce anti-D, with an obstetric indication.
■ 
 Amniocentesis, chorionic villus sampling, and 
intrauterine fetal blood sampling
■ 
 Antepartum haemorrhage (or unexplained 
uterine pain)
■ 
 External cephalic version (performed or 
attempted)
■ 
 Abdominal trauma sufficient to cause FMH
■ 
 Ectopic pregnancy
■ 
 Molar pregnancy
■ 
 Intrauterine death or stillbirth
■ 
 Miscarriage, threatened miscarriage
■ 
 Termination of pregnancy
Anti-D immunoglobulin dose: 625 IU (125 µg)
Postpartum prophylaxis6
A RhD negative woman, not previously immunised 
to produce anti-D, who gives birth to a RhD positive 
baby.
Anti-D immunoglobulin dose: 625 IU (125 µg) with 
additional dose(s) indicated where fetomaternal 
haemorrhage is > 6 mL fetal red cells

1 Routine antenatal anti-D prophylaxis (RAADP) should be administered regardless of, and in addition to, 
prophylaxis given for a potentially sensitising event.
2 A sample for antibody testing should be taken prior to administration of anti-D immunoglobulin at 28 weeks.
3 Before 12 weeks gestation, in cases of either spontaneous complete miscarriage where the uterus is 
not instrumented or mild painless vaginal bleeding, the risk of fetomaternal haemorrhage is negligible.
4  For multiple pregnancies the recommended anti-D immunoglobulin dose is 625 IU (125 µg).
5 Routine antenatal prophylaxis does not preclude prophylaxis for a potentially sensitising event. 
6 Routine antenatal prophylaxis or prophylaxis for a potentially sensitising event does not preclude postpartum 
prophylaxis.
Laboratory Assessment of Fetomaternal Haemorrhage (FMH)
■  
The Kleihauer acid elution test is widely used to test for FMH and can detect 
bleeds of 0.1 mL or less. False results can occur with the test and it is less 
reliable in the first two trimesters of pregnancy when there is an increase in the 
level of fetal haemoglobin in the maternal red blood cells. Clinicians using this 
test should be aware of these limitations. Anti-D immunoglobulin should still be 
administered if a negative Kleihauer test is obtained.
■  
There is no need to assess the size of FMH in pregnancies of 20 weeks gestation 
or less, as the standard 250 IU (up to and including 12 weeks) and 625 IU 
(beyond 12 weeks, up to and including 20 weeks) dose of anti-D immunoglobulin 
will sufficiently cover the maximum likely FMH for the gestation. 
■  
It is appropriate to assess the size of FMH after 20 weeks gestation. A blood 
sample should be taken from the mother as soon as possible after the potentially 
sensitising event and before the dose of anti-D immunoglobulin is given. 
Transfusion Medicine Handbook 3rd Edition 
Page 121

■  
Results reporting the fetal bleed in mL of red cells should be promptly available 
so that anti-D immunoglobulin can be given within 72 hours of the FMH.
■  
For large bleeds greater than 4 mL, repeat testing should be performed at 48 
hours following each intravenous dose of anti-D or 72 hours following each 
intramuscular dose of anti-D immunoglobulin to check for clearance of fetal 
red cells and, if still positive, additional dose(s) given.
■  
Flow cytometry, a more accurate and reproducible method for measuring FMH, 
is not yet widely available.
Timing, Dose and Route of Anti-D Immunoglobulin
■  
Anti-D immunoglobulin prophylaxis should be given as soon as possible and 
always within 72 hours of a potentially sensitising event.
■  
If anti-D immunoglobulin has not been offered within 72 hours, a dose given 
within 10 days may provide some protection.
■  
A 625 IU dose of anti-D immunoglobulin will protect against a FMH of up to 
6 mL of RhD positive red cells (equivalent to 12 mL of blood). Where testing 
shows that a FMH of greater than 6 mL has occurred, additional dose(s) of 
anti-D immunoglobulin must be administered. In this situation, the recommended 
minimum dose is 100 IU per mL RhD positive red cells. 
■  
Where more than 1250 IU of anti-D immunoglobulin (two 625 IU vials of Rh(D) 
Immunoglobulin-VF) is indicated, consultation with a NZBS Transfusion Medicine 
Specialist is recommended.
■  
For bleeds requiring a large anti-D immunoglobulin dose, the maximum 
recommended administration rate is 3000 IU every 8 hours to reduce the risk of 
an adverse reaction arising from rapid clearance of fetal RhD positive red cells. 
As it is recommended that no more than 4 mL is injected intramuscularly at each 
site, Rhophylac®, an anti-D immunoglobulin product suitable for intravenous 
administration, may be an appropriate alternative.
■  
Recipients who have a moderate or severe thrombocytopenia should not 
receive intramuscular injections. The standard anti-D immunoglobulin provided 
by NZBS, Rh(D) Immunoglobulin-VF, is suitable for intramuscular use only. It 
may be given by intramuscular or subcutaneous route; it must not be given 
intravenously. Rhophylac, an anti-D immunoglobulin product suitable for 
intravenous administration is held at NZBS sites and can be obtained following 
consultation with a NZBS Transfusion Medicine Specialist/Medical Officer. 
■  
There is some evidence to suggest that intramuscular administration of anti-D 
immunoglobulin may be associated with an increased risk of lack of effect in 
patients with a body mass index (BMI) > 30. An Expert Panel Consensus Position 
Statement (available online at www.transfusion.com.au/node/612) provides 
recommendations regarding the use of anti-D immunoglobulin in these patients.
The following is recommended where a woman has received an appropriate dose of 
anti-D immunoglobulin followed by a further risk event for immunisation.
■  
Where the previous dose was given 2 or more weeks before, a further dose(s) 
of anti-D immunoglobulin should be offered. 
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■  
Where the previous dose was given less than 2 weeks before, a further dose of 
anti-D immunoglobulin should be offered where the pregnancy is more than 20 
weeks gestation. Where testing indicates a FMH greater than 6 mL, additional 
dose(s) of anti-D immunoglobulin must be administered.
■  
Where there is continual uterine bleeding that is judged clinically to represent the 
same risk event, further dose(s) of anti-D immunoglobulin should be offered at a 
minimum of 6 weekly intervals. In pregnancies > 20 weeks gestation, estimation 
of FMH should be undertaken at 2 weekly intervals and the presence of fetal 
cells should prompt an additional anti-D immunoglobulin dose to cover the 
volume of FMH. 
Further observations and comment on the guidelines for the use of anti-D 
immunoglobulin are available in the NZBS Clinical Compendium.
Non-invasive Fetal Genotyping
A maternal blood sample may be used for non-invasive testing of cell-free fetal DNA 
to predict the fetal red cell phenotype. This has particular value in identifying a fetus 
that is unlikely to be at risk of HDFN. In the case of a sensitised RhD negative woman, 
the absence of the RhD gene predicts for a RhD negative fetus. As such, aggressive 
monitoring of the mother’s anti-D titre and the health of the fetus is unnecessary. Fetal 
RhD status is also useful in determining whether anti-D immunoglobulin prophylaxis 
is required. Rarely, such as when genetic changes lead to gene silencing rather than 
deletion, genotype determination does not correlate with the antigen expression on 
the fetal red cells.
Certain criteria need to be met before obtaining fetal DNA for genotyping; the mother’s 
serum contains an IgG antibody of potential clinical significance and the father is, or 
may be, heterozygous for the gene encoding the antigen of interest. Fetal genotyping 
for RhD, C, c, E and Kell is available for suitable patients. A NZBS Transfusion Medicine 
Specialist can be consulted on whether it is appropriate to refer samples for testing.
6.10   Intrauterine Transfusion (IUT)
Intrauterine red cell transfusion is used to correct fetal anaemia resulting from red cell 
alloimmunisation (most commonly due to anti-D followed in order of importance by 
anti-c and anti-K) and less commonly red cell aplasia due to fetal parvovirus infection. 
Similarly, intrauterine platelet transfusions are used to correct fetal thrombocytopenia 
due to platelet alloimmunisation. The goal of IUT is primarily to prevent (or treat) fetal 
hydrops, ensuring the fetus reaches a viable gestational age and can be delivered. 
Cellular components for IUT must be irradiated.
Consultation with a NZBS Transfusion Medicine Specialist is required to access these 
components. The specification for the component will be agreed in advance with the 
fetomaternal specialist and information on the actual composition of the component 
provided at the time of delivery of the product. 
The general specification for red cell and platelet components for use in IUT are as 
follows:
Transfusion Medicine Handbook 3rd Edition 
Page 123

Table 6.11: Component Requirements for IUT
Component
Requirements
Red cells
■ 
 Group O (low titre IgG anti-A, -B) or ABO identical with fetus (if 
group known)
■ 
 RhD negative (if HDFN due to anti-c or other antibodies, may be 
RhD positive)
■ 
 IAT crossmatch compatible with maternal plasma (antigen 
negative for relevant antigen)
■ 
 < 5 days old
■ 
 CMV negative
■ 
 Irradiated 
■ 
 Haematocrit 0.75 - 0.90
Platelets
■ 
 Group O (low titre IgG anti-A, -B) or group specific/compatible with 
maternal antibody
■ 
 HPA-compatible with maternal antibody
■ 
 Collected by apheresis where possible
■ 
 CMV negative
■ 
 Irradiated
■ 
 Volume required (mL) =  Desired plt increment  x Feto-placental BV2 
 
Plt count of concentrate
■ 
 Concentrated to platelet count 2000 - 4000 x 109/L
■ 
 Rate of transfusion 1 - 5 mL/min 
1See Table 4.5: Red Cell Components Available from NZBS. 
2Blood Volume (BV).

6.11   Transfusion of the Newborn
Red Cells
Normal blood volume at birth varies according to gestational age and timing of clamping 
of the cord. For term infants the average blood volume is 80 mL/kg whilst in pre-term 
infants it is higher at 106 mL/kg. The newborn bone marrow does not respond as 
rapidly as an adult and any uncorrected blood loss can rapidly lead to anaemia. 
A significant cause of anaemia in neonates is iatrogenic blood loss associated with 
laboratory testing. Neonates are also at increased risk of infection and these factors 
must influence transfusion medicine practice, especially in premature infants. 
The volume of red cells to be transfused in newborns depends on the weight of the baby 
and local policy. International guidelines recommend a volume for top-up transfusion 
of 10 - 20 mL/kg (although some neonatal units use the range 8 - 12 mL/kg) at an 
infusion rate of 5 mL/kg/hr. Frusemide given at a dose of 1 mg/kg halfway through 
the transfusion may sometimes be required to minimise volume load. 
In some centres it is practice to minimise the number of donors to which a newborn is 
exposed. NZBS provides small volume ‘neonatal’ red cell units (each typically containing 
70 mL) which are produced by separating an adult ‘plasma-reduced’ red cell donation 
into a number of equal-sized aliquots. All (or some) of the individual aliquots from one 
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adult unit can be reserved for sequential transfusions to the same baby over the full 
35-day shelf life of the red cells. Fresh frozen plasma and platelet concentrates are 
also available in neonatal volumes. 
Compatibility Testing
The normal rules for ABO and RhD compatibility apply. However, for infants up to the 
age of 4 months, maternal blood may be used for pretransfusion testing provided the 
ABO groups of mother and infant are compatible since any clinically significant red 
cell antibody present in the infant’s circulation will have come from the mother. Blood 
components selected for transfusion should be compatible with any ABO or other red 
cell antibody present in the maternal or infant plasma. Repeated transfusions during 
the infant’s first 4 months of life do not require further compatibility testing if there are 
no atypical maternal red cell antibodies in the maternal or infant plasma. However, 
if the antibody screen is positive, full pretransfusion testing and crossmatching will 
be necessary.
Pretransfusion testing of infants 4 months or older should be performed on a sample 
from the infant.
Exchange Transfusion  
For severe cases of HDFN, neonatal exchange transfusion may be required. 
Table 6.12: Red Cell Component Requirements for Neonatal Exchange Transfusion
Red Cell Requirements For Exchange Transfusion1
■ 
 Group O or ABO compatible with maternal and infant plasma
■ 
 RhD negative (or RhD identical with the infant)
■ 
 Negative for red cell antigens against which maternal antibody is directed
■ 
 IAT crossmatch compatible with maternal plasma
■ 
 < 5 days old 
■ 
 CMV negative
■ 
 Irradiated, especially if infant has previously received IUT
■ 
 Haematocrit 0.5 - 0.60
■ 
 Transfusion volume: 80 - 160 mL/kg for term infants and 100 - 200 mL/kg for 
preterm infants, guided by clinical indication
1See Table 4.5: Red Cell Components Available from NZBS. 
Special Requirements 
Neonates less than 1500 g in weight or immunosuppressed for other reasons should 
be given ‘CMV safer’ blood components as an added precaution. The use of either 
prestorage leucodepletion or selection of CMV-antibody negative blood components 
significantly reduces the risk of CMV transmission and CMV disease in susceptible 
recipients. However, neither method alone or in combination can completely avoid 
transmission from the occasional donor with CMV viraemia in the “window” period 
prior to the development of antibodies following acute infection or when reactivation 
of latent infection occurs.
Transfusion Medicine Handbook 3rd Edition 
Page 125

In some situations irradiated blood components may be indicated for neonatal 
transfusions. Irradiation removes the small risk of transfusion-associated graft-vs-host 
disease (TA-GVHD) in at-risk patients by inactivating donor lymphocytes. 
When there is clinical suspicion of a congenital cellular immunodeficiency state such as 
severe combined immunodeficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome, 
ataxia telangiectasia or partial deletion of chromosome 22 (del 22q11.2), use of 
irradiated components is mandatory. Features associated with immunodeficiency 
states include cardiac defects, dysmorphic features, craniofacial abnormalities, 
hypocalcaemia and lymphopenia. 
Irradiated components are not indicated for ‘top-up’ transfusions of premature or term 
infants unless there has been a previous IUT, in which case irradiated components 
should be administered until 6 months after the 40 week gestation date. 
Irradiated components may also be appropriate for extreme low body weight neonates 
less than 28 weeks who are at increased risk of TA-GVHD due to physiological 
immune incompetence. Evidence suggests that the risk is greatest in those < 900 g 
in body weight.
As a result of gamma irradiation, red cells lose potassium during storage. While this 
is not normally a problem with small volume neonatal top-up transfusions, for larger 
volume and exchange transfusions irradiated red cells must be transfused within 24 
hours of irradiation.
Use of Erythropoeitin 
In some infants erythropoietin (EPO) may be used to reduce transfusion requirements. 
Specialist advice on dose and frequency should be obtained.
Platelets
There is an increased risk of haemorrhage in preterm infants with moderate 
thrombocytopenia  < 50 x 109/L and in full-term infants with platelet counts less 
than 20 - 30 x 109/L. The risk is increased if sepsis or coagulopathy are present. 
The recommended volume for top-up transfusion is 10 mL/kg to a maximum of 
one neonatal unit. A single neonatal platelet unit will normally provide an acceptable 
platelet increment in children under 10 kg in body weight. At higher body weights, one 
single neonatal platelet unit per 10 kg of body weight followed by a post-transfusion 
platelet count and reassessment of the patient is recommended. If the plasma volume 
of the platelet concentrate is excessive, the blood bank may be asked in advance 
for advice regarding the need to remove plasma to a minimum volume of 10 - 15 mL 
per platelet concentrate.
6.12   Neonatal Autoimmune Thrombocytopenia
Neonates with thrombocytopenia associated with maternal autoimmune disease (e.g., 
immune thrombocytopenia or systemic lupus erythematosis) generally have a benign 
postnatal course without bleeding complications and one in which often a nadir is 
reached by day 2 - 3, followed by a spontaneous rise in platelet count by the seventh 
day. In a small number of cases treatment is warranted due to persistent severe 
thrombocytopenia. Most neonates respond well to intravenous immunoglobulin in a 
dose of 2 g/kg body weight. Platelet transfusions have no value in prophylaxis of this 
condition but may be useful if there is bleeding.
Page 126 
Transfusion Medicine Handbook 3rd Edition

6.13  Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)
FNAIT is a rare but serious condition which arises from maternal alloimmunisation 
to fetal platelet antigens of paternal origin and which affects approximately 1:1,100 
pregnancies. FNAIT is the platelet equivalent of HDFN, where maternal IgG antibodies 
cross the placenta and may destroy fetal platelets, leading to thrombocytopenia and 
an increased risk of bleeding. The most serious consequence, estimated to occur 
in 10 - 20% of untreated pregnancies and presenting at any time from 20 weeks 
gestation until a few days after birth, is intracranial haemorrhage (ICH) which may be 
fatal or lead to long-term neurological problems. 
The most common alloantibody responsible for FNAIT in Caucasians is anti-HPA-1a 
(80 - 90% of cases) followed by anti-HPA-5b (5 - 15%), with other HPA antibody 
specificities are infrequently seen. In Maori and Asian mothers, consideration should 
be given to other antibodies including those within the HPA-4 system.
There may or may not be a history of thrombocytopenia in a previous infant. Unlike 
HDFN, FNAIT can occur during a first pregnancy and in fact almost half of the clinical y 
evident cases are discovered in the first live-born infant. 
Treatment 
The management of FNAIT is overseen by a fetal medicine specialist along with input 
from a specialist haematologist and/or NZBS Transfusion Medicine Specialist.
In the neonatal period the condition is self-limiting often resolving within two weeks after 
birth although occasionally persisting for up to eight weeks. The treatment of choice 
is platelet transfusion for which platelets lacking the specific HPA antigen should be 
selected. In the absence of suitable donor platelets, the mother’s platelets may be 
used. These must be washed to remove the plasma that contains the platelet antibody 
and must be irradiated. Such a selected donation must follow the usual procedures 
for collecting, testing, storing, handling and transfusing of the unit that apply to non-
selected blood donations.
For well neonates with suspected FNAIT, no evidence of haemorrhage, and where 
the platelet count is < 30 x 109/L, prompt transfusion of platelets negative for both 
HPA-1a and HPA-5b antigens is recommended. Following the results of serological 
testing, directed donations negative for the implicated antigen are recommended. 
Where there is evidence of ICH or other major haemorrhage, a higher platelet threshold 
50 - 100 x 109/L should be used. The platelet count should be maintained > 50 x 
109/L at least until the end of the first week of life. In view of the poor outcome of 
FNAIT-associated ICH, if HPA antigen-negative or washed maternal platelets cannot be 
provided, current BCSH guidelines recommend the transfusion of randomly selected 
platelets (irrespective of their HPA status). Intravenous immunoglobulin (IVIg) is an 
alternative therapy, although there is often a 24 to 48 hour delay in response, and may 
be used in combination with platelet transfusion. Treatment of the neonate with high 
dose intravenous immunoglobulin (2 g/kg body weight) is effective in about 65% of 
cases and can reduce the period of dependence on compatible platelets. 
For women with a history of FNAIT, management of the fetus during a subsequent 
pregnancy includes assessment of ICH risk (including paternal HPA zygosity +/- fetal 
HPA genotyping), antenatal administration of IVIg 1 - 2 g/kg/week from as early as 
12 weeks, and/or corticosteroids. Despite immune modulating therapy, there remains 
Transfusion Medicine Handbook 3rd Edition 
Page 127

an increased risk of fetal ICH. For cases considered to be at high risk of ICH (such 
as a previous child with FNAIT-associated ICH), prophylactic intrauterine fetal platelet 
transfusions may be included in the management. 
 
6.14  Individuals Refusing Blood Transfusion
Some patients may refuse to receive transfusion for personal, religious or cultural 
reasons. For example, Jehovah’s Witnesses may hold beliefs that preclude transfusion 
of blood components or fractionated products. These wishes and beliefs must be 
respected and patients treated in a non-emotional and logical way. 
Some patients will refuse all blood transfusions while others will accept fractionated 
products. Others will accept autologous blood collection and transfusion, cell salvage 
and auto-transfusion of blood collected during surgery. Some patients do not wish 
their relatives or peers to know that they have been transfused. 
When a patient indicates that they do not wish to receive a transfusion there should be 
close and confidential discussion with the patient as to their exact requirements and 
what they will and will not accept. This information should be recorded in their notes. 
It is advisable that the matter is discussed with the clinical leader of the unit concerned. 
Where there are areas of difficulty or dissension, the Chief Medical Officer (CMO) of 
the hospital should be contacted for further advice and guidance as to management 
of the patient. The CMO will have access to the DHB solicitor and appropriate patient 
advocate groups. Additional consultation may be necessary with anaesthetists and 
surgeons to ensure the best possible care is given to the patient when blood transfusion 
cannot be provided despite clear clinical indication.
For children, the same procedure should be followed with careful consultation of the 
parents and noting any comments or opinions from the child. For babies and infants, 
the clinical leader should be closely involved in the decision-making. In cases where 
the parents, whanau or guardians refuse consent for transfusion deemed necessary to 
save life, prevent permanent injury or prolonged and avoidable pain and suffering, the 
consultant responsible needs to consult with the CMO to discuss appropriate further 
action. Such action may involve meeting with a solicitor to discuss the need for legal 
action. If court action is deemed necessary, an inter partes hearing may be appropriate. 
It is mandatory that a very careful procedure be followed, with full documentation and 
consultation with the relevant people, prior to any transfusion.
Page 128 
Transfusion Medicine Handbook 3rd Edition

7
ADVERSE EFFECTS OF TRANSFUSION 
7.1 Overview
Transfusion, like other treatments, can both benefit and harm the patient. Good clinical 
practice depends on understanding both the benefits and risks that transfusion may 
carry. Also, it is essential to consider the potential benefits and risks of not using a 
blood component or fractionated product, or of using an alternative. 
Blood transfusion has become safer as infectious hazards have been identified and 
donor selection procedures, viral screening tests and platelet pre-release bacterial 
culture systems have been introduced. There has also been continuous improvement 
in manufacturing processes for fractionated products. 
Although much effort is placed into ensuring the safety of transfusion, preventable 
clerical error and inappropriate transfusion still account for a significant proportion of 
reported transfusion-related adverse events.
Data on the occurrence of adverse reactions and other adverse events associated 
with the transfusion process are collected through NZBS Haemovigilance.
7.2 
Reporting Adverse Reactions and Events 
Serious or life-threatening acute reactions are rare but new or unexpected symptoms 
that appear while the patient is being transfused must not be overlooked, as they may 
be early warning signs of a serious reaction. 
Severe reactions are most likely to occur within 15 minutes of starting a transfusion. 
It is important to monitor the patient closely during this initial period and thereafter at 
regular intervals according to local hospital policy. Serious events should be discussed 
with a NZBS Transfusion Medicine Specialist/Medical Officer or specialist haematologist 
for advice on further management of the patient, laboratory investigations and future 
transfusion requirements. 
Adverse reactions to blood components  
If the patient experiences an adverse reaction during or following transfusion of a blood 
component, clinical staff must report this to the blood bank as soon as possible. NZBS 
supplies a Transfusion-related Adverse Reaction Notification form that has guidelines 
for the management of adverse transfusion reactions to assist clinical staff in the 
immediate care of the patient. 
The completed form should be sent to the blood bank along with remnants of the 
transfused components and laboratory samples required for full investigation of the 
reaction. Refer to Table 10.1: Samples Required  for Pretransfusion Testing for further 
information.
Adverse reactions to fractionated products 
If the patient experiences an adverse reaction to a fractionated plasma product this 
must be reported to the blood bank as soon as possible, for example by sending a 
NZBS Transfusion-related Adverse Reaction Notification form. The blood bank will 
then initiate completion of a NZBS Notification of Adverse Reaction to a Fractionated 
Product
 form together with information obtained from the patient’s clinician.
Transfusion Medicine Handbook 3rd Edition 
Page 129

In accordance with pharmacovigilance requirements, NZBS reports the occurrence of 
adverse reactions to fractionated products to the relevant manufacturer, for example 
CSL Behring. Where clusters of similar adverse reactions occur, these are reported 
to the New Zealand regulator, Medsafe. Both Medsafe and the Centre for Adverse 
Reactions Monitoring (CARM) are provided with an annual NZBS Haemovigilance 
Report.
Adverse events associated with transfusion 
The blood bank should be notified as soon as possible if it is believed that the patient 
has received a wrong blood component or fractionated product, received one 
intended for another patient, that the transfusion did not meet requirements or that 
the transfusion was inappropriate. It should be noted that the patient may not always 
experience or show a ‘reaction’ in these situations.
Page 130 
Transfusion Medicine Handbook 3rd Edition

eatment for 
eaction is mild and 
opriate tr
ecipient identity
e not appr
etic Paracetamol 1g po and monitor 
oids ar
  Check label and r
  Slow the transfusion if r
MO elects to continue transfusion
  Send Haemovigilance notification to Blood 
Bank 
  Antipyr
closely
  Ster
FNHTR
Management
 
 
 
 
 





etic 

ent 
ecurr

oduction and 
epeated minor 
e r
ed 
ed
evious transfusion 
etransfusion antipyr
evention
  Check for history of 
pr reactions. Consider  pr Paracetamol 1g po  wher reactions occur and  further transfusions ar requir
  Consult TMS if r
reactions occur 
  Note: All blood 
components ar depleted of leucocytes  during pr further leucodepletion  at the bedside is not  requir
Pr
 
 
 



 
 
 
 
ransfusion Reactions
 
 
 
 
ransfusion Reactions

  e rise
 

e rise
esent: 
<1.5°C
espiratory
etransfusion
 unexplained 
e rise of at least 
om pr
dia, headache, 
etransfusion baseline,
 unexplained fever
 unexplained fever
e:
ess and haemodynamic
≥38°C and a 
ehension, loin pain, 
  Mild: ≥38°C and a temperatur of at least 1°C but  from pr occurring in the absence of chills, rigors, r distr instability   Moderate: fever  temperatur 1°C but not meeting criteria  for either mild or sever FNHTR   Sever >39°C and a temperatur ≥2.0°C fr baseline and chills/rigors   Associated or secondary  symptoms may be pr tachycar nausea, flushing, anxiety hypertension or occasionally  hypotension    In some cases: marked  appr and/or angina
Signs & Symptoms
 
 
 
 
 





reaction 
 1-3:100 
Guidelines for the Management of Adverse T
 Reaction induced by  cytokines
 Alloimmune  to leucocyte  antigens
 Other causes may  exist
 
 
 
  Common
  Onset during or within 
4 hours following  transfusion
 
equency:
 
 
7.3
Table 7.1: Guidelines for the Management of Adverse T
Reaction/Cause
Febrile Non-Haemolytic  Transfusion Reaction  (FNHTR)
Fr
(higher in multi-transfused 
recipients)


 
 
 
Transfusion Medicine Handbook 3rd Edition 
Page 131


eat as a moderate or 
ecipient identity
ease tr
eaction
esume
e r
eased monitoring, e.g., BP/TPR every 15-
oublesome
  Slow transfusion
  Check label and r
  Antihistamine, e.g., Loratadine 10mg 
or Cetirizine 10mg po if symptoms ar
tr
  If symptoms mild and transient, transfusion 
may r
  Continue transfusion at a slower rate with 
incr
30 min
  Send Haemovigilance notification to Blood 
Bank
  If symptoms incr
sever
Management
 
 
 
 
 
 
 








ophylaxis 
ent mild 
ophylaxis 
ecipients befor
ecurr
evention
  For r
reactions pr
with antihistamine to 
alleviate symptoms, e.g., 
Loratadine 10mg or 
Cetirizine 10mg po
  Routine pr
for all r
transfusion is not 
indicated
Pr
 
 


ransfusion Reactions continued
eaction:
  Flushed skin 
  Morbilliform rash with itching
  Urticaria (hives)
  Localised angioedema
  Periorbital itch, erythema 
and oedema
  Conjunctival oedema
  Minor oedema of lips, 
tongue and uvula
Signs & Symptoms
Minor or localised r
 
 
 
 
 
 
 







otein 
oduct 
eacting 
 1:100 – 1:500
e common with 
 Recipient may have 
an antibody r
with plasma pr
or leucocyte antigen 
(HLA or other) in 
the transfused 
component or 
fractionated pr
 
  Mor
plasma and platelet 
components
  Onset during or within 
4 hours following 
transfusion
equency:
Reaction/Cause
Allergic Reaction (minor)
Fr
 
 


 
Table 7.1: Guidelines for the Management of Adverse T
Page 132 
Transfusion Medicine Handbook 3rd Edition

ocortisone may be 
eat symptomatically 
omethazine 25-50mg IV 
eactions with TMS 
ecipient identity
ed with IV fluids, oxygen and 
ed
equir
  Stop transfusion
  Check label and r
  Replace IV set and give saline to keep vein 
open and/or maintain BP
  Monitor closely and tr
as r
antihistamine, e.g., Pr
(max rate 25mg/min) or Loratadine 10mg or 
Cetirizine 10mg po. Hydr
consider
  Send Haemovigilance notification to Blood 
Bank
  Discuss moderate r
Management
 
 
 
 
 
 







event 
ophylactic 
eactions but 
esent
ent
ocortisone will 
eliably pr
eatment with an 
evention
  Discuss with TMS if 
recurr
  Note: Pr
tr
antihistamine or 
hydr
not r
moderate and sever
allergic r
may alleviate symptoms 
when pr
Pr
 
 


ransfusion Reactions continued
ead 
e common
dia
e anxiety
  Symptoms as for minor 
reactions, plus:
  Cough
  Mild hypotension or 
tachycar
  Dyspnoea and oxygen 
desaturation ar
  Chills and rigors
  Loin pain and angina
  Sever
Signs & Symptoms
Moderate or widespr
reaction:
 
 
 
 
 
 
 







oduct
may 
otein or 
  1:500 – 
1:5,000
 Recipient 
have an antibody 
reacting with a 
plasma pr
leucocyte antigen 
(HLA or other) in 
the transfused 
component or 
fractionated pr
 
  Onset usually within 
first 50-100mL infused 
and within 4 hours of 
transfusion
equency:
Reaction/Cause
Allergic Reaction 
(moderate)
Fr
 ■
 
Table 7.1: Guidelines for the Management of Adverse T
Transfusion Medicine Handbook 3rd Edition 
Page 133

 
 
 
 
   
 
 
 
 
 
 
esent and eatment
ns to normal
en 20mL/kg, until  
etur
epeat at 5-10 min
esent (r
eactions
e r
e contraindicated
 
ecipient identity
ed:
ocortisone 4mg/kg (200-400mg
eactions with TMS
equir
e r
0.5mg/0.5mL
en 0.01mg/kg IM; min dose 0.1mL,
 hours)
>90mmHg, then titrate
enalin 1:1000 IM and r
 Adult: 
 Childr max dose 0.5mL
 
omethazine ar
 Adr intervals if r
saline, e.g., adults 2L, childr SBP 
IV)
Cetirizine 10mg po for itch or angioedema
added for sever
Pr
AP ventilation, chest x-ray
  Stop transfusion
  Check label and r
  Follow Anaphylaxis Guidelines:
• 
•  Replace IV set and give rapid IV colloid or
•  Consider Hydr
•  Consider H1-antihistamine, e.g., Loratadine or
•  H2-antihistamine, e.g., Ranitidine may be
•  Note: Sedating antihistamines, e.g.,
  CP
  ICU liaison
  Follow NZRC Guidelines if no pulse pr
for symptoms that persist after initial tr
  Collect serum tryptase sample within 1-2 hours
if anaphylaxis may be pr within 6-8
  Send Haemovigilance notification to Blood Bank
  Discuss sever
Management
 
 
 
 
 
 
 
 
 



 
 
 
 
 
 
 
 






     
 

 
   
ecipient is
 
e the
 
eaction is
oducts may be
opriate if r
ashed cellular
evention
  IgA deficient blood/
blood pr appr known to have absolute IgA deficiency and to have anti-IgA
  W
components may be indicated wher cause of the r not identified
Pr
Discuss with TMS befor requesting:
 
 


 
 
 
 
 
ransfusion Reactions continued
, change in
 
eaction:
ecipients
dia
ead urticaria with
e hypotension, shock
e anxiety
eatening r
 
idespr
  Symptoms as for moderate
reactions, plus:
  Sever
and tachycar
  W
skin flushing and itching
  Wheezing, stridor
voice
  Sever
  Note: Respiratory
symptoms may dominate in anaesthetised r
Signs & Symptoms
Life-thr
 
 
 
 
 
 






 
 
 
 
 
 
 
   
   
e)
may
otein
otein
  1:20,000 – 1:50,000
oduct, e.g., IgA,
 Recipient  have an antibody reacting with a plasma pr in the transfused component or fractionated pr haptoglobin or other plasma pr
 
  Rapid onset
equency:
Reaction/Cause
Anaphylactic /  Anaphylactoid Allergic  Reaction (sever
Fr
 ■
 
Table 7.1: Guidelines for the Management of Adverse T
Page 134 
Transfusion Medicine Handbook 3rd Edition

esolved
  Stop transfusion
  Replace the IV infusion set and infuse saline 
to manage BP
  Symptomatic management until r
  Send Haemovigilance notification to Blood 
Bank
Management
 
 
 
 




evention
Pr

ransfusion Reactions continued
 systolic BP 
and
 hour of completing 
>30mmHg during or 
  Hypotension – fall in systolic 
BP 
within 1
transfusion 
<80mmHg
Signs & Symptoms
 ■
eased 
incr
 1-2:1,000
idiosyncratic 
  Often 
reaction
  Possible 
risk with ACE-
inhibitor therapy
  Onset during or within 1 
hour of transfusion
equency:
Reaction/Cause
Hypotensive Reaction
Fr
 ■
 
 
Table 7.1: Guidelines for the Management of Adverse T
Transfusion Medicine Handbook 3rd Edition 
Page 135

e with 
essur
ed
eat if clinically 
enal and liver function, 
ecipient identify
etic, e.g., Frusemide 1-2mg/kg IV and/or 
ocortisone may be consider
  Stop transfusion
  Check label and r
  Replace IV set and start normal saline
  Treat shock and maintain blood pr
IV saline infusion
  Investigate possible DIC and tr
significant bleeding
  Diur
Mannitol, may help maintain urine flow
  Hydr
  Samples to assess r
DIC and haemolysis, e.g., full blood count, 
unconjugated bilirubin, LDH and haptoglobin
  Send Haemovigilance notification to Blood 
Bank
Management
 
 
 
 
 
 
 
 
 










s ID 
ecipient’
ecipient of 
ecipient’
eful monitoring of 
e and handle blood 
etransfusion blood 
oper administration of 
evention
  Meticulous checking 
of r
and labelling of 
pr
sample at r
side
  Meticulous two-person 
checking of ID of 
intended r
blood component and 
component label
  Car
recipient for first 15 min 
of each unit transfused
  Stor
components within 
specifications 
  Pr
blood components 
Pr
 
 
 
 
 





ransfusion Reactions continued
Co
>1
dia
, jaundice
 haemoglobinuria
  Unexplained fever 
  Chills, rigors
  Pain up arm
  Chest, abdominal or low 
back pain
  Dyspnoea
  Tachycar
  Hypotension, shock
  Haemoglobinaemia 
and
  Oliguria with dark urine or 
anuria
  Nausea, vomiting
  Diarrhoea
  Pallor
  Bleeding (due to DIC)
Signs & Symptoms
Some or all of –
 
 
 
 
 
 
 
 
 
 
 
 
 













ed 
ed 
handling, 
  1:12,000 – 
1:100,000
, ABO 
ely
oper 
  ABO or other 
incompatible r
cell transfusion 
reaction caused by 
complement-fixing 
antibodies
  Rar
antibodies in a 
platelet or plasma 
component
  Impr
storage or 
administration of r
cell component
  Onset within 24 hours, 
usually immediate
equency:
Reaction/Cause
Acute Haemolytic 
Transfusion Reaction
Fr
 ■
 
 
 
Table 7.1: Guidelines for the Management of Adverse T
Page 136 
Transfusion Medicine Handbook 3rd Edition

ed)
een (may be 
ed)
ed cells clear
oup antibody scr
eaction is suspected
ed cells clear
ect antiglobulin test (may be negative when 
  Investigate haemolysis: 
  Full blood count with film comment
  Dir
most r
  Blood gr
negative until r
  Liver function tests
  Haptoglobin concentration falls while 
haemolysis is occurring
  LDH 
  Send Haemovigilance notification to Blood 
Bank if r
Management
 
 
 
 
 
 
 
 









ed 
oup antibodies 
ded on the 
ecor
ovided for futur
oviding compatible 
e r
evention
  Blood gr
ar
NZ Blood Service 
national database so 
that compatible r
cell components can 
be pr
transfusions
  Note: Delay may occur 
in pr
red cells for transfusion
Pr
 
 



ransfusion Reactions continued
esent 
om destruction of 
een shows 
ely splenomegaly
e cases
ocytes may be pr
orsening anaemia and  W jaundice fr red cells  Often asymptomatic  but rar haemoglobinaemia and  haemoglobinuria  Renal impairment may occur  in sever  Blood scr unexpected anaemia and  spher on film
Signs & Symptoms
 
 
 
 




esults 
 days

essing 
eported 
has 
oup 
oduces a 
ed cells
 
egnancy
elevant 
eviously been 
  Recipient 
pr
sensitised to 
a blood gr
antigen, usually 
by transfusion 
or pr
Transfusion with 
red cells expr
the r
antigen pr
secondary immune 
response and r
in haemolysis of 
transfused antigen-
positive r
  Onset usually 1-7 days 
post-transfusion but 
may be up to 28
equency:
Reaction/Cause
Delayed Haemolytic 
Transfusion Reaction
Fr
Estimated 1:5,000 but 
recognized and r
events 1:35,000
 ■
 
Table 7.1: Guidelines for the Management of Adverse T
Transfusion Medicine Handbook 3rd Edition 
Page 137

or 
penicillin 
ecipient if sepsis 
om r
es fr
oad-spectrum 
br

es on blood component and 
antibiotics: 
  Stop transfusion
  Replace IV set; give saline to maintain BP 
and/or keep vein open 
  Send Haemovigilance notification to Blood 
Bank 
  Notify Blood Bank by phone and contact TMS 
urgently 
  Obtain blood cultur
suspected
  Give 
cephalosporin and gentamicin 5mg/kg 
  Note: Blood Bank will arrange urgent Gram 
stain and cultur
report any positive findings
Management
 
 
 
 
 
 
 







ed 
e and handle 
oducts for any 
ed or leaking 
e transfusing:
 a visibly clumped 
platelet component
 an unusually dark r
cell component
 punctur
bag
evention
  Collect, stor
blood components 
within specifications 
  Inspect pr
visual abnormality or 
defect in unit container 
befor
• 
• 
• 
Pr
 
 


 
 
 
ransfusion Reactions continued
ed cell 
ess, 
Yersinia 
 sepsis
, chills, fever
  Rigor
  Shock, usually within 
minutes of starting 
transfusion
  Respiratory distr
wheezing and oxygen 
desaturation
  Pain up arm 
  Chest and back / loin pain 
  Nausea, vomiting
  Explosive diarrhoea 
may occur with 
enterocolitica
  Most common infecting 
agents: staphylococcal 
species (platelet 
components), gram 
negative species (r
components) 
Signs & Symptoms
 
 
 
 
 
 
 
 








ely 
esent, 
own to a 
e pr
ed cells 
  
component 
commonly 
fects platelet 
fects r
  Blood 
contains bacteria 
that have gr
high concentration
  Most 
af
components; rar
af
  If gram negative 
bacteria ar
endotoxin levels may 
be very high
  Rapid onset
equency:
Reaction/Cause
Bacterial Sepsis
Fr
Platelet components: 
<1:10,000 
Red cell components: 
<1:250,000
 ■
 
 
 
Table 7.1: Guidelines for the Management of Adverse T
Page 138 
Transfusion Medicine Handbook 3rd Edition

etic (Frusemide 
AP ventilation
ecipient upright with legs over side of 
  Stop transfusion 
  Seek urgent medical assessment
  Sit r
bed, administer oxygen, diur
1-2mg/kg IV), CP
  Phlebotomy may be necessary
  Send Haemovigilance notification to Blood 
Bank
Management
 
 
 
 
 





ed
ecipient
eserve 
 in Units
ecipients 
equir
not
etic 
escribe 
diovascular or 
ed or a large 
en, and r
opriate for r
diovascular r
void elective 
evention
  Restrictive transfusion 
practice
  Monitor fluid balance 
esp. in elderly and 
childr
with car
renal disease
  Transfuse at a rate 
appr
  Give a diur
immediately prior 
to a transfusion if 
car
is impair
transfusion is r
  A
transfusions at night
  Always pr
paediatric transfusion 
dose in mL, 
Pr
 
 
 
 
 
 







ransfusion Reactions continued
ess 
essur
diac silhouette 
dia
espiratory distr
eased blood pr
oductive cough with pink 
diac collapse
  Acute r
along with some or all of 
the following: dyspnoea, 
oxygen desaturation, 
pr
frothy sputum, nausea, 
restlessness and anxiety
  Tachycar
  Incr
  Acute or worsening 
pulmonary oedema on chest 
xray
  Enlarged car
on chest xray
  Evidence of fluid overload 
such as positive fluid 
balance, raised JVP and/or 
CVP
  Note: Hypotension may 
occur in cases of acute 
car
Signs & Symptoms
 
 
 
 
 
 
 







ed 
culatory 
ed cell 
recipient 
transfused 
:  
eat for 
ecipient
ransfusion-
diovascular or 
 Elderly 
with impair
car
renal function
 Transfusion too rapid 
for r
 Volume 
too gr
recipient, especially 
if normovolaemic 
  Onset during or within 
6 hours following 
transfusion
Main risk factors:
• 
• 
• 
equency
  
Reaction/Cause
TACO: T
Associated Cir
Overload
Fr
1:100 – 1:1,000 r
transfusion episodes
 ■
 
 
 
Table 7.1: Guidelines for the Management of Adverse T
Transfusion Medicine Handbook 3rd Edition 
Page 139


ecipient 
A antigen 
elevant HP
ombocytopenia in the 
eatments 
ecommended
e thr
A antibodies
ombocytopenia or clinically 
oids and plasma exchange ar
e thr
eatening bleeding – platelet 
e desirable
void random-donor platelet transfusion
  Consult TMS or haematologist if a r
of cellular blood components develops an 
unexpected sever
following 1-2 weeks 
  Test for HP
  If not bleeding – monitor 
  If sever
significant bleeding – intravenous 
immunoglobulin is r
  Corticoster
recognised additional tr
  If life-thr
components lacking the r
ar
  A
Management
 
 
 
 
 
 
 







e selected 
oviding 
omptly so that 
equir
evention
  Restrictive transfusion 
practice
  Notify Blood Bank and 
TMS pr
relevant investigations 
can be initiated 
  Further transfusions 
may r
components 
  Note: Delay may 
occur in pr
further cellular blood 
components
Pr
 
 
 
 




ransfusion Reactions continued
ombocytopenia 
e thr
ombocytopenia will 
  Sever
often with purpura and 
possibly other bleeding 
  Thr
persist for 1-2 weeks
Signs & Symptoms
 
 


A). The 
has 
culating 
  
oduced an 
  Recipient 
pr
antibody to a human 
platelet-specific 
antigen (HP
antibody forms 
immune complexes 
with transfused 
platelet antigens 
resulting in clearance 
of most cir
platelets 
  Onset about 5-12 
days after transfusion 
of cellular blood 
components
equency:
egnant)
Reaction/Cause
Post-transfusion Purpura
Fr
<1:100,000 (mostly occurs  in women who have been  pr
 ■
 
Table 7.1: Guidelines for the Management of Adverse T
Page 140 
Transfusion Medicine Handbook 3rd Edition


ecipient 
A antigen 
ed
espiratory 
equir
elevant HP
ombocytopenia in the 
eatments 
ecommended
e thr
e management for r
A antibodies
ombocytopenia or clinically 
oids and plasma exchange ar
e not usually helpful
e thr
eatening bleeding – platelet 
e
etics ar
e desirable
void random-donor platelet transfusion
  Consult TMS or haematologist if a r
of cellular blood components develops an 
unexpected sever
following 1-2 weeks 
  Test for HP
  If not bleeding – monitor 
  If sever
significant bleeding – intravenous 
immunoglobulin is r
  Corticoster
recognised additional tr
  If life-thr
components lacking the r
ar
  A
  Intensive car
failur
  Diur
  Send Haemovigilance notification to Blood 
Bank 
  Notify Blood Bank by phone and contact TMS 
urgently 
  Tissue typing samples will be r
Management
 
 
 
 
 
 
 







Management
 
 
 
 
 






AS) 
testing 
om FFP 
om the 
e selected 
oviding 
educed by 
esis platelet 
omptly so that 
equir
Male-only FFP 
 HLA-antibody 
of apher
donors
 Pooled platelets ar
suspended in platelet 
additive solution (P
and have minimal 
residual plasma
evention
  Restrictive transfusion 
practice
  Notify Blood Bank and 
TMS pr
relevant investigations 
can be initiated 
  Further transfusions 
may r
components 
  Note: Delay may 
occur in pr
further cellular blood 
components
evention
  Restrictive transfusion 
practice
  NZ case-rate fr
and platelet components 
has been r
supply of: 
• 
• 
• 
  Notify Blood Bank 
so that donor(s) can 
be assessed for 
relevant antibodies and 
implicated donor(s) 
withdrawn fr
active donor panel
Pr
 
 
 
 




Pr
 
 
 


 
 
 

ransfusion Reactions continued
ess 

oductive 
e) along 
om:
ombocytopenia 
espiratory distr
oceeding to 
eaction occurs 
e thr
ombocytopenia will 
culatory overload)
 TACO
 other causes of acute 
lung injury (ALI)
  Sever
often with purpura and 
possibly other bleeding 
  Thr
persist for 1-2 weeks
  Acute r
(often pr
respiratory failur
with some or all of the 
following: dyspnoea, oxygen 
desaturation, non-pr
cough, chills, fever and 
hypo- or hypertension.
  Bilateral infiltrates on chest 
xray 
  Absence of left atrial 
hypertension (as in 
cir
  If the r
during anaesthesia the 
lungs become very stif
from rapidly developing 
pulmonary exudate
  Distinguish fr
• 
• 
Signs & Symptoms
 
 


Signs & Symptoms
 
 
 
 
 





 
 
 
 
 
 
 
 
 
 
 
esults
oup 
ecipient

A). The 
has 
culating 
om ARDS
ders 
  
 <1:5,000
contributing 
recognised
ophil (HNA)
ovascular lung
 
oduced an 
ransfusion-
  Recipient 
pr
antibody to a human 
platelet-specific 
antigen (HP
antibody forms 
immune complexes 
with transfused 
platelet antigens 
resulting in clearance 
of most cir
platelets 
  A complex gr
of disor
indistinguishable 
clinically fr
  One 
mechanism involves
a donor antibody
reacting with r
leucocyte (HLA) or
neutr
antigens causing cell
activation that r
in acute sever
micr
injury
  Other 
factors likely exist
  Onset about 5-12 
days after transfusion 
of cellular blood 
components
  Onset within 6 hours 
following transfusion 
of plasma or plasma-
containing cellular 
components 
equency:
egnant)
equency:
Reaction/Cause
Post-transfusion Purpura
Fr
<1:100,000 (mostly occurs  in women who have been  pr
 ■
 
Reaction/Cause
TRALI: T
Related Acute Lung 
Injury
Fr
 ■
 
 
 
Table 7.1: Guidelines for the Management of Adverse T
Transfusion Medicine Handbook 3rd Edition 
Page 141

  Consult TMS or haematologist to investigate 
and establish diagnosis
  Send Haemovigilance notification to Blood 
Bank 
Management
 
 


esidual 
otocol to 
equiring 
s transfusion 
d
evention
  Irradiate cellular 
blood components 
to inactivate r
lymphocytes
  When notified of 
a patient r
irradiation of cellular 
components, NZBS 
attaches a pr
the patient’
recor
Pr
 
 


ransfusion Reactions continued
ome with 
, rash, liver dysfunction, 
  Clinical syndr
fever
diarrhoea and pancytopenia 
Signs & Symptoms
 ■
cellular 
and 
elative
lymphoma
donation 
nucleoside 
A-GVHD)
  
esis platelets
ected 
ersus-Host 
ell-defined risk factors 
 Congenital  immune deficiency
 Intrauterine  transfusion and  neonatal exchange  transfusion
 Hodgkin 
 Autologous  allogeneic HSCT
 Dir from blood r
 HLA-matched  apher
 Granulocyte  transfusion 
 Purine  analogue therapy
 Alemtuzumab  therapy
  Onset 1-6 weeks 
following transfusion
 W include:
• 
• 
• 
• 
• 
• 
• 
• 
• 
equency: e but fatal
 
Reaction/Cause
Transfusion-Associated  Graft-V Disease (T
Fr Rar
 ■
 
 
 
 
 
 
 
 
 
Table 7.1: Guidelines for the Management of Adverse T
Page 142 
Transfusion Medicine Handbook 3rd Edition


ed, infuse 
ement
equir
ecipient and monitor 
e measur
om the r
e temperatur
es cor
ough a warmer
  Limit heat loss fr
BP/TPR
  If further blood components r
thr
  Note: Reliable determination of temperatur
requir
Management
 
 
 




e the 
e is 
oduce 
er’
ough a 
e will pr
ect temperatur
operly maintained and 
evention
  Give large fluid 
infusions thr
warmer designed for 
rapid infusion of blood 
components and follow 
the manufactur
instructions
  Equipment must be 
pr
validated to ensur
corr
achieved as excessive 
temperatur
haemolysis
Pr
 
 


ransfusion Reactions continued

opic 
egularity 
ed platelet function 
diac rhythm irr
fect
  Reduced temperatur
  May be associated with 
car
and a negative inotr
ef
  Impair
and coagulation
Signs & Symptoms
 
 
 



en)
e than 
essive onset 
ogr
oducts (mor
  Pr
during rapid infusion of 
large volumes of cold 
fluids, including blood 
pr
50mL/kg/h in adults or 
15mL/kg/h in childr
equency: no data
Reaction/Cause
Cooling
Fr
 ■
Table 7.1: Guidelines for the Management of Adverse T
Transfusion Medicine Handbook 3rd Edition 
Page 143

7.4 
Febrile Non-Haemolytic Transfusion Reaction
Fever or rigors during red cell transfusion affect 1 - 3% of recipients and in the past 
were usually attributed to the transfusion of white cells present in blood components. 
Febrile non-haemolytic transfusion reactions (FNHTR) generally occur more frequently in 
patients who have been alloimmunised to leucocyte antigens as a result of pregnancy 
or recurrent transfusion. The use of leucocyte-depleted blood components has 
undoubtedly reduced the occurrence of FNHTR, however the relatively large number 
of reactions still seen suggests the involvement of other mechanisms and risk factors. 
Febrile reactions during platelet transfusion have been attributed to leucocyte- and 
platelet-derived cytokines that accumulate in the product during storage.
Classical symptoms of FNHTR are shivering, usually 30 - 60 minutes after the start 
of the transfusion, followed by fever. Most reactions can be managed by slowing 
or stopping the transfusion and giving an antipyretic such as paracetamol. FNHTR, 
although unpleasant, are not life-threatening, however it is important to remember fever 
or rigors can also be the early symptoms of a severe acute haemolytic transfusion 
reaction or transfusion of bacterially contaminated blood.
Recurrent severe FNHTR in patients who require repeated transfusion of red cells or 
platelets may be prevented by the use of washed cellular components. 
Premedication
While treatment of FNHTR with antipyretics such as paracetamol for a symptomatic 
rise in temperature may be justified, routine premedication with antipyretics and/or 
antihistamines prior to transfusion is not advised as it is both unnecessary and may 
modify important signs of a transfusion reaction. Steroids are not appropriate for the 
treatment or prevention of FNHTR.
7.5 
Allergic & Anaphylactic Reaction
Allergic reactions represent a spectrum of severity from mild, where the patient simply 
experiences isolated urticaria or a rash, though to fatal anaphylactic shock.
Allergic reaction 
These are typified by one or more of the following: urticaria, rash, allergic dyspnoea 
(stridor, cyanosis, wheezing), localised angioedema or generalised pruritis without 
hypotension during or within 4 hours of transfusion. These reactions are commonly 
associated with transfusion of components with large volumes of plasma, for example 
platelets and FFP. Since the introduction of platelets suspended in platelet additive 
solution (PAS), the frequency of allergic reactions has reduced. 
Symptoms usually subside if the transfusion is slowed and parenteral antihistamine 
is given. The transfusion may be continued if there is no progression of symptoms 
after 30 minutes. 
A rise of mast cell tryptase can support the diagnosis of an allergic reaction.
Anaphylactic reaction  
These are rare but life-threatening complications usually occurring during or very 
shortly after transfusion and are differentiated from mild/moderate allergic reactions 
by severity where, in addition to mucocutaneous features, there is airway compromise 
Page 144 
Transfusion Medicine Handbook 3rd Edition

or severe hypotension requiring vasopressor treatment (or associated symptoms like 
hypotonia or syncope).
Anaphylaxis may occasionally be associated with antibodies against IgA in patients 
who have extremely low levels of IgA in their plasma or other genetic variants of 
plasma proteins. If this is the suspected cause the patient should, if possible, not 
be transfused. Special components will be needed in consultation with an NZBS 
Transfusion Medicine Specialist.
Premedication 
Treatment with an antihistamine or hydrocortisone for generalised allergic reactions 
is justified. Premedication may be appropriate before transfusing a patient who has 
previously experienced repeated allergic reactions. Routine premedication with 
antihistamines prior to transfusion is however not advised, as it is both unnecessary 
and may modify important signs of a transfusion reaction.
7.6 
Hypotensive Transfusion Reaction
Hypotensive transfusion reactions are defined as a drop in systolic blood pressure 
≥ 30 mmHg during or within one hour of transfusion together with a systolic blood 
pressure ≤ 80 mm Hg. Most reactions occur very rapidly within minutes of starting 
the transfusion and respond to ceasing the transfusion together with supportive care. 
The underlying condition of the patient must have been excluded as an explanation 
for the reaction. These may occur more frequently in patients receiving angiotensin-
converting enzyme (ACE) inhibitor therapy. 
7.7 
Acute Haemolytic Transfusion Reaction 
Incompatible transfused red cells react with the patient’s anti-A or anti-B antibodies and 
cause an acute haemolytic transfusion reaction (AHTR). Such a reaction can activate 
complement and cause disseminated intravascular coagulation (DIC) and acute renal 
failure. The reaction is usually most severe if group A red cells are transfused to a 
group O patient. Transfusion of ABO-incompatible blood almost always arises from 
pretransfusion sample labelling errors or from failure to perform required checks prior 
to giving the transfusion. If red cells are administered to the wrong patient (i.e., any 
patient other than the one for whom the red cells were supplied) the chances of ABO-
incompatibility are about 1 in 3. Rarely, AHTR is due to a non-A, non-B, complement-
fixing antibody. Such reactions reported most commonly involve the Kell, Duffy and 
Kidd antigen group systems.
Acute haemolysis may also occur following transfusion of plasma-rich blood 
components such as platelets or FFP from donors with high titres of anti-A or anti-B 
that react with patient red cells. 
In a conscious patient even a few mil ilitres of incompatible blood may cause symptoms 
within a few minutes of starting the transfusion. The patient may become restless or 
distressed and experience pain at the infusion site, fever, flushing, breathlessness, or 
abdominal, flank or substernal chest pain. The severity varies widely as it is dependent 
on the titre of blood group antibody in the recipient, the quantity of blood transfused 
and other factors such as age. In an unconscious or anaesthetised patient, hypotension 
and uncontrollable bleeding due to DIC may be the only signs of an incompatible 
transfusion. Oliguria is common and is often followed by acute renal failure. 
Transfusion Medicine Handbook 3rd Edition 
Page 145

If AHTR is suspected, the transfusion must be stopped, the line maintained with 
intravenous saline and urgent steps taken to confirm or exclude this possibility. 
Signs and symptoms of AHTR may be similar to a severe allergic reaction or bacterial 
contamination. In addition, autoimmune haemolytic anaemia due to erythrocyte 
autoantibodies in the recipient and non-immune (mechanical) causes must be part 
of the differential diagnosis.
7.8 
Delayed Haemolytic Transfusion Reaction
A delayed haemolytic transfusion reaction (DHTR) is one in which evidence of increased 
red cell destruction develops, usually between 24 hours and 28 days, following a 
transfusion. The symptoms and clinical or laboratory signs are similar to AHTR but are 
usually less severe, often manifesting as an inadequate rise or unexplained fall in the 
post-transfusion haemoglobin. Whilst clinically significant DHTR are rare and seldom 
fatal, they can cause additional problems for a patient who is already seriously ill. 
DHTR occur in a patient immunised to a red cell antigen by an earlier transfusion 
or pregnancy. The level of antibody may be so low that it cannot be detected in the 
pretransfusion sample. After transfusion of red cells bearing the target antigen, a 
rapid secondary immune response boosts the antibody level so that, after a few days, 
transfused red cel s bearing the relevant antigen may be rapidly destroyed. Antibodies 
of the Kidd and Rh systems are the most frequent cause of DHTR.
7.9 
Bacterial Sepsis
Bacterial sepsis, whilst rare, is the leading microbial cause of transfusion mortality. 
Sources of bacteria in blood components may include contamination from skin 
organisms at the phlebotomy site due to ineffective skin disinfection, skin plugs 
introduced to units during phlebotomy, transient bacteremia in donors and, rarely, 
contamination during handling and processing of components. 
Bacterial contamination is more likely in components stored at room temperature (20 
- 24°C) such as platelets, than with red cells (stored at 2 - 6°C). Common organisms 
associated with contamination include Staphylococcus epidermidis, Staphylococcus 
aureus, Bacillus cereus
, Group B streptococci, Escherichia coli, Pseudomonas species 
and other gram-negative organisms. Sepsis due to contaminated platelets is thought 
to be both under recognised and under reported. Platelet-associated sepsis is not 
normally catastrophic and can occur several hours or longer post-transfusion making 
it difficult to associate with transfusion and thereby diagnose. This is in contrast to the 
sepsis and toxaemia from bacterially contaminated red cells which is often rapid and 
catastrophic, with reported mortality rates of up to 60%. 
Septic and toxic reactions may be life threatening. If bacterial contamination is 
suspected, the transfusion must be stopped immediately and institutional guidelines 
for investigating a reaction strictly followed. Usual investigation will include urgent 
patient and blood unit culture and Gram stain. Initial treatment involves managing the 
haemodynamic complications of sepsis and administration of intravenous antibiotics 
covering the usual pathogens associated with transfusion-related sepsis. 
A number of measures are used by NZBS to minimise the risk of bacterial contamination 
in blood components. These include:
Page 146 
Transfusion Medicine Handbook 3rd Edition

■  
Predonation identification and deferral of potentially bacteraemic donors
■  
Enhanced disinfection of the skin at the phlebotomy site
■  
Diversion of the initial 10 - 40 mL blood collected into a separate container
■  
Bacterial monitoring of platelet components using an automated bacterial 
detection system
Visual inspection of the blood component for abnormal appearance (such as 
discoloration or haemolysis) should be carried out both prior to release from the 
Blood Bank and before administration. Blood components must not be transfused 
beyond their expiry date.
7.10  Post-transfusion Purpura
Post-transfusion purpura (PTP) is a rare but potentially lethal complication of 
transfusion of red cells and platelets. It is characterised by the sudden onset of severe 
thrombocytopenia, typically 5 - 12 days following transfusion, often associated with 
haemorrhage. PTP is most often seen in females (90% of cases) and in particular 
those with a history of pregnancy. 
Transfusion causes an anamnestic response boosting human platelet-specific antigen 
(HPA) antibodies previously stimulated by pregnancy or earlier transfusion. The resulting 
thrombocytopenia is due to alloantibody-mediated destruction of the transfused 
platelets as well as “bystander” destruction of the patient’s own platelets. 
Treatment of choice is high dose intravenous immunoglobulin, 2 g/kg body weight, 
administered in divided doses over 2 - 5 consecutive days. 
Plasma exchange and corticosteroids have been used in the past but an increase in 
platelet count is significantly delayed when compared to intravenous immunoglobulin. 
If platelet transfusion is unavoidable, platelets that are compatible with the patient’s 
antibody should be used although survival of the platelets may be impaired during the 
acute phase of the syndrome. If future transfusions are planned, red cell or platelet 
components from donors negative for the implicated HPA antigen(s) should be selected 
wherever possible. 
Expert advice from a NZBS Transfusion Medicine Specialist or specialist haematologist 
is needed when managing PTP.
7.11  Transfusion-Associated Circulatory Overload
When too much fluid is transfused or the transfusion is too rapid for a patient, fluid 
overload can lead to systemic and pulmonary venous engorgement. Cardiogenic 
pulmonary oedema and acute respiratory failure may follow. 
The features of transfusion-associated circulatory overload (TACO) include acute 
respiratory distress, tachycardia, increased blood pressure, evidence of fluid overload, 
an enlarged cardiac silhouette and new or worsening pulmonary oedema in the chest 
xray. TACO usually occurs within 6 hours of completion of the transfusion. Evidence 
of fluid overload may include a documented positive fluid balance and/or a clinical 
response to diuretic therapy. Diagnosis is supported by an elevated serum B-type 
natriuretic peptide (BNP) or the accompanying N-terminal fragment (NT-pro BNP) to 
Transfusion Medicine Handbook 3rd Edition 
Page 147

more than 1.5 times the pretransfusion value (if available) and/or an increase in mean 
arterial pressure or increase pulmonary wedge pressure. 
Standard medical treatment includes stopping the transfusion, sitting the patient 
upright, administering oxygen and diuretic therapy. Where necessary, vasodilator 
therapy and/or non-invasive ventilatory support with continuous positive airways 
pressure (CPAP) may be helpful. Venesection can also be considered.
TACO is most commonly seen in patients with low body weight, the elderly, infants 
or children, those with a history of cardiac, respiratory or renal insufficiency, and in 
the setting of red cell transfusion for chronic anaemia. Volume overload is a special 
risk with albumin solutions. 
Patients with chronic anaemia are normovolaemic or hypervolaemic and may have 
signs of cardiac failure before any fluid is infused. Each unit should be given slowly and 
the patient closely observed. Preemptive diuretic therapy may be helpful. 
7.12  Transfusion-Related Acute Lung Injury
Transfusion-related acute lung injury (TRALI) is a significant transfusion-related 
event. Although poorly recognised and undoubtedly underreported, international 
haemovigilance data indicates that it is one of the most common causes of fatal 
transfusion reactions.
TRALI is characterised by acute respiratory distress due to non-cardiogenic 
pulmonary oedema, developing during or within 6 hours of transfusion. Typically, 
plasma components containing antibodies against the patient’s white blood cells are 
implicated. Transfusion is followed by a (usually) severe reaction with acute respiratory 
distress, accompanied by chills and/or fever. The chest xray shows numerous, mainly 
perihilar, nodules with infiltration of the lower lung fields without cardiac enlargement 
or engorgement of the vessels. A transient leucopenia or neutropenia may be seen. 
The implicated donors are almost always al oimmunised multiparous women. However 
the number of reactions seen where antibodies are either not identified or serologically 
cannot be implicated suggests the involvement of other mechanisms and risk factors.
The diagnosis of TRALI is therefore a clinical and radiographic diagnosis and is not 
dependent on the results of laboratory tests or any proposed pathophysiologic 
mechanisms. TRALI should be considered a clinical syndrome rather than a disease 
with single cause. Treatment usually involves intensive care respiratory support.
Reporting to the NZBS Transfusion Medicine Specialist is essential so that an implicated 
donor can be removed from the panel. 
Testing of donors implicated in TRALI events 
One proposed mechanism for TRALI is the interaction between human leucocyte 
antigen (HLA) or neutrophil-specific (HNA) antibodies of donor origin and the recipient’s 
white cells. NZBS has developed a standard procedure for investigating TRALI events, 
including relevant serological testing. The investigation includes testing of the donor(s) 
and recipient for HLA class I and II antibodies (identifying specificity if detected) and 
for HNA antibodies. Antibody detection and identification is complemented by HLA 
typing to confirm presence of the corresponding antigen(s). A crossmatch between 
donor serum and recipient white cells is also useful, with a positive result strongly 
implicating the particular donor(s). 
Page 148 
Transfusion Medicine Handbook 3rd Edition

TRALI risk reduction 
A number of countries, including New Zealand, have introduced a strategy for reducing 
the frequency of TRALI involving the use of FFP manufactured from plasma collected 
only from male donors. The use of male-only donors for FFP appears to reduce 
the incidence of TRALI. In addition, female plateletpheresis donors with a history of 
pregnancy to > 20 weeks gestation are tested for the presence of HLA antibodies. 
Where positive, donors are deferred from donating apheresis platelets and whole 
blood donations are excluded from processing to platelet pools.
The differential diagnosis of TACO and TRALI 
Acute respiratory distress during or shortly following transfusion may be due to TACO, 
TRALI, a severe allergic reaction or the patient’s underlying condition. Unfortunately, 
many of the early signs and symptoms are not discriminatory and can occur in other 
types of transfusion reactions. Most FNHTR and allergic reactions can however be 
readily identified as such.
It is important to distinguish between TACO and TRALI because of the relatively high 
mortality for TRALI. Invasive measurements such as central venous and pulmonary 
wedge pressures may be useful (elevated in TACO) but are not consistently diagnostic 
or readily available, particularly in less severe cases. It has been suggested that 
measurement of serum B-type natriuretic peptide (BNP) or the accompanying 
N-terminal fragment (NT-pro BNP) might be useful in the differential diagnosis of TACO. 
BNP is secreted from the cardiac ventricles as a result of ventricular pressure overload 
and volume expansion, such as occurs with TACO. Low levels of BNP can help exclude 
TACO however, whilst high levels may favour TACO they do not necessarily exclude 
TRALI or allergic reactions, as these can co-exist. 
7.13  Transfusion-Associated Dyspnoea
Only a minority of transfusion reactions are associated with predominantly respiratory 
features however these are some of the most serious transfusion-related adverse 
events. Included in this group are TACO, TRALI and allergic reactions, particularly of 
the more severe type. 
The term transfusion-associated dyspnoea (TAD) is used by haemovigilance 
programmes to record events with significant respiratory distress, occurring within 24 
hours of transfusion, that do not meet the criteria of TRALI, TACO or allergic reaction 
nor are explained by the patient’s underlying condition.
7.14  Transfusion-Associated Graft-Versus-Host Disease
Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare complication of 
transfusion caused by engraftment and proliferation of transfused donor T-lymphocytes 
which destroy recipient cells carrying “foreign” human leucocyte antigens (HLA). 
Immunodeficient patients such as allogeneic bone marrow transplant recipients 
receiving cellular components and fetuses receiving intrauterine transfusions are at 
special risk for this disease. TA-GVHD has also occurred in immunologically normal 
patients after transfusion of blood from a relative. 
TA-GVHD is fatal in almost all cases. Acute TA-GVHD begins from 4 - 40 days after 
transfusion with high fever followed by a diffuse erythematous skin rash progressing 
to erythroderma and desquamation. Gastrointestinal and liver dysfunction occur and, 
unlike GVHD following stem cell transplants, pancytopenia is common. 
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TA-GVHD is prevented by gamma irradiation of cellular blood components (red cells 
and platelets) to a minimum dose of 25 Gray (Gy) targeted to the central position of 
the container and 15 Gy to all other parts of the container. The irradiation dose must 
not exceed 50 Gy.
For further information regarding irradiation of blood components see Section 4.6: 
Irradiation.
7.15  Iron Overload / Haemosiderosis
Transfusion-dependent patients receiving red cells over a long period become 
overloaded with iron. Chelation therapy may be used to minimise or reverse 
accumulation of iron for these patients.
7.16  Transfusion-Related Immunosuppression 
Allogeneic blood transfusion has been shown to cause suppression of the recipient’s 
immune system. However, the mechanism behind the effect and the consequences 
resulting from such transfusion-related immunomodulation (TRIM) remain unclear, 
with contradictory evidence provided by both individual studies and metanalyses 
performed to date. 
Evidence from a number of studies suggests that allogeneic blood transfusion 
enhances the survival of renal allografts, increases the recurrence rate of resected 
malignancies, increases the incidence of postoperative bacterial infections and 
increases the postoperative mortality rate from causes other than postoperative 
infection. 
7.17  Transfusion-Transmitted Infection
The perception of the risks of transfusion have been greatly influenced by HIV 
transmissions that occurred before today’s safer testing procedures were available.
Blood donors, like anyone else, can occasionally carry an infectious agent, sometimes 
for a long period, without having any clinical signs or symptoms. For this reason 
donors are interviewed at each and every visit and laboratory tests are performed on 
every blood donation. No part of the donation can be released until all these tests are 
known to be clear. Computer blood management systems (BMS) are used to ensure 
that this process is strictly adhered to.
There is very good evidence that with the donor selection and testing procedures used 
by NZBS, the risk in New Zealand of infection through the contamination of blood 
components and fractionated products is extremely small. 
Table 7.2: Estimated Residual Risk of Transfusion-Transmitted Infection in New Zealand 
Agent
Mean Window 
Residual Risk (with 95% prediction 
Period (days)
intervals)
HIV
5.6
1 in 9.2 million donations (2.5 - 33 million)
HCV
3.1
1 in 6.9 million donations (3.6 - 12 million)
HBV1
23.9
1 in 0.8 million donations (0.4 - 1.4 million)
1 HBV residual risk does not take into account the risk from occult HBV nor the proportion of recipients who 
are HBV-immune from vaccination or past infection.
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7.18  Other Infectious Agents
There are a number of other viral and parasitic infections that can be transmitted by 
transfusion, for example malaria (Plasmodium species), Chagas disease (Trypanosoma 
cruzi
), Dengue, Zika and West Nile viruses. These are not endemic in New Zealand 
but a blood donor may be exposed or become infected during travel or residence 
abroad. The risk of acquiring Creutzfeldt-Jakob disease (CJD) and variant CJD from 
blood transfusion remains very low and neither has ever been reported in New Zealand. 
Rare cases have been reported in the UK.
It is important for NZBS to identify at-risk donors who will then either be selectively 
deferred from donating or tested for evidence of infection. 
7.19  Adverse Event Data 
The NZBS National Haemovigilance Programme has been collecting data regarding 
transfusion-related adverse events (TRAE) since 2005. The imputability scores of 
adverse events have been recorded since 2008. From January 2008 to December 
2013, a total of 2756 events having an imputability score ≥3 were reported for 
transfusions involving 207,361 recipients who between them received 918,918 red 
cell, platelet or frozen plasma components. The following table outlines the type and 
frequency of TRAE during the period 2008 - 2013.
Table 7.3:  Frequency of Transfusion-Related Adverse Events (Imputability1 3) Reported 
to New Zealand Haemovigilance 2008 - 2013
Per 100,000 
Per 10,000 
Event
Number
Components 
Recipients 
Transfused
Transfused
FNHTR
1152
125.4
55.6
Allergic
920
100.1
44.4
UCT
179
19.5
8.6
TACO
119
13.0
5.7
IBCT
84
9.1
4.1
TAD
76
8.3
3.7
DSTR
60
6.5
2.9
Hypotension
60
6.5
2.9
DHTR
36
3.9
1.7
Inappropriate 
transfusion

26
2.8
1.3
TRALI
13
1.4
0.6
Acute reaction2
12
1.3
0.6
Pain
10
1.1
0.5
TTI
9
1.0
0.4
All Events
2,756
299.9
133.0
1 Imputability  3: the event is possibly, probably or certainly attributable to transfusion.
2Includes acute haemolytic and other severe acute transfusion reactions.
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Key
FNHTR  
Febrile non-haemolytic transfusion reaction
Allergic  
Allergic transfusion reaction
TACO  
Transfusion-associated circulatory overload
IBCT  
Incorrect blood component transfused
UCT  
Unclassifiable complication of transfusion
TAD  
Transfusion-associated dyspnoea
DSTR  
Delayed serologic transfusion reaction
DHTR  
Delayed haemolytic transfusion reaction
TRALI  
Transfusion-related acute lung injury
TTI 
Transfusion-transmitted infection
7.20  Other Complications
Complications associated with large volume transfusions including hypocalcaemia, 
hyperkalaemia, hypothermia, disturbances of acid base balance and adult respiratory 
distress syndrome are considered in Section 6.3: Complications of Acute Blood Loss 
Associated with Large Volume Transfusions
.
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8
CLINICAL ALTERNATIVES AND APPLICATIONS
There are no effective alternatives to red cells, platelets, white cells, haemopoietic 
progenitor cells, plasma and most fractionated products. 
In this section, the emphasis, with some exceptions, is directed towards minimising 
exposure to allogeneic blood components. One such option is the collection and 
transfusion of autologous blood components, namely red cells, platelets, fresh or frozen 
plasma and some blood constituents such as serum eye drops. Practices which include 
preoperative collection, acute normovolaemic haemodilution (ANH) and perioperative 
salvage are all essentially modifications of routine blood transfusion practice. However, 
the circumstances where these procedures are indicated or applicable are limited.
8.1 
Autologous Blood Collection and Transfusion
Using autologous blood will avoid the risks of alloimmune complications of transfusion and 
may reduce the risk of many transfusion-transmitted infections. Autologous transfusion 
does not however reduce the risk of bacterial infection associated with transfusion.
Autologous blood can be collected several ways, including:
■  
Preoperative collection where blood is collected from the patient during the 
weeks leading up to their surgical procedure. This should only be performed 
in exceptional clinical circumstances. In general, this is limited to patients 
undergoing an elective procedure normally requiring a blood transfusion 
(otherwise units of blood collected are likely to be wasted) where there are 
clinical, religious or cultural reasons for preferring autologous blood. The 
inevitable reduction in preoperative hemoglobin level increases the likelihood 
that any intra- or post-operative blood transfusion (autologous or allogeneic) 
may be required. 
 
Autologous blood components obtained by preoperative donation are collected, 
prepared and stored under the same conditions as allogeneic blood. Acceptance 
of these individuals may vary from that of regular donors for allogeneic use, 
particularly with reference to age. The preferred programme for obtaining up to 
four units of blood involves collections at weekly intervals from approximately 
four weeks before surgery, with the last unit collected no later than one week 
before surgery. Most patients will require supplementary iron during the period 
of autologous collections to maintain the haemoglobin > 110 g/L. The patient 
will be required to pay for autologous collections unless this is undertaken for 
clinical, religious or cultural reasons. The charge covers the costs of collection, 
processing and testing of the units. Patients wishing to donate autologous blood 
prior to surgery should initially discuss this with their surgeon who should in turn 
liaise with a NZBS Transfusion Medicine Specialist. 
■  
Frozen autologous blood where red cells and platelets are collected from patients 
with rare blood groups or multiple antibodies and then frozen for future use.
■  
Acute normovolaemic haemodilution (ANH) where a patient donates whole 
blood immediately before surgery, which is then replaced with intravenous colloid 
or crystalloid solution to maintain normovolemia. The removed whole blood is 
usually returned within several hours, for example at wound closure, providing 
fresh clotting factors and platelets. 
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■  
Red cell salvage
Intraoperative blood salvage: where blood is collected from the surgical site 
using a cell-saver machine and reinfused after processing (washing and filtering) 
during or after surgery.  
 
Post-operative blood salvage: where blood is collected from wound drains and 
reinfused. The salvaged blood may be processed before reinfusion to minimise 
potential coagulation problems sometimes seen with unprocessed blood. 
 
ANH and red cell salvage are usually performed under the supervision and the 
responsibility of anaesthetists and/or surgeons.
8.2 
Non-Blood Plasma Volume Expanders 
The judicious use of plasma volume expanders can result in adequate restoration of 
blood volume at an economic cost. 
It should be noted however that positive fluid balance is an independent predictor 
of poor outcome in ICU patients and this, together with the increasing adoption of 
permissive hypotension (hypotensive resuscitation) in a number of clinical settings, is 
leading to more restrictive intravenous fluid administration in the critically ill than has 
been used in the past.
Crystalloid Solutions
Initial resuscitation should be with 1 - 3 litres of a crystalloid solution such as Plasmalyte 
148, pH 7.4 (an isotonic non-calcium containing ‘balanced’ solution buffered with 
acetate) or 0.9% sodium chloride (‘normal’ saline). Adequate crystalloid resuscitation 
may often avert the need for other plasma expanders. Colloid products can then be 
used in the recommended doses. If prolonged volume expansion is required, such as 
in a severely ill trauma patient, then the use of albumin solutions rather than synthetic 
colloids is likely to be justified.
Plasmalyte 148 in 5% glucose, dextrose solutions and compound sodium lactate (CSL) 
solutions, e.g., Hartmann’s or Ringer-Lactate, must not be administered simultaneously 
with a red cell infusion as the solutions are not compatible. No drugs or additives, other 
than 0.9 % sodium chloride intravenous infusion, are recommended to be mixed with 
red cells before or during transfusion.
Synthetic Colloid Solutions
Colloids should only be used if crystalloids are insufficient to stabilise a patient. Due 
to the risk for acute renal damage and a requirement for dialysis, the use of synthetic 
colloids, particularly starch solutions, should be avoided in critically ill patients and 
those with sepsis or pre-existing renal dysfunction. In these situations, and where 
colloids are required, the use of albumin solutions is likely to be justified.
Gelatin Solutions (Gelofusal®) 
Gelofusal® is a 4% solution of succinylated gelatin prepared from heat degraded 
cattle bone gelatin. It has an average molecular weight of 30,000 Dalton. Gelofusal® 
has a volume-expansion effect that lasts three to four hours. The frequency of severe 
acute reactions, which are usually anaphylactic, is < 1/10,000 and patients should be 
closely monitored at least while the first 20 - 30 mL are infused. The maximum volume 
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that can be infused has not been determined but is at least 3 - 5 litres. Apart from a 
dilutional effect on coagulation proteins, haemostasis is not affected. Gelofusal® does 
not interfere with blood group analysis and cross-matching procedures.
Gelofusal® must not be administered simultaneously with a red cell infusion, as the 
solution is not compatible.
Hydroxyethyl Starch (Voluven® 6%; Volulyte® 6%) 
Hydroxyethyl starch (HES) solutions provide an alternative colloidal fluid to albumin 
and plasma for use in plasma volume expansion. HES solutions are prepared from 
chemically modified amylopectin. 
Voluven® 6% and Volulyte® 6% are solutions of HES in 0.9% sodium chloride. The 
average molecular weight is 110,000 - 150,000 Dalton. Infusion results in a plasma 
volume increase of approximately 100% of the infused volume and the effect lasts four 
to six hours. The frequency of severe acute reactions, which are usually anaphylactoid, 
is 1/10,000 - 1/1000 and patients should be closely monitored at least while the first 
10 - 20 mL are infused. With the administration of Voluven disturbances of blood 
coagulation, beyond dilutional effects, can occur. The maximum volume recommended 
before this product interferes with coagulation is about one litre per day. 
8.3 
Oxygen Carrying Compounds
Although red cell substitutes in the form of haemoglobin-based oxygen carriers, 
including polymerised haemoglobin and haemoglobin conjugated with polyethylene 
glycol, and perfluorocarbon oxygen carriers have been under investigation for many 
years, there is no indication that these compounds will be widely available for routine 
use in the near future. 
8.4 
Haemopoietic Growth Factors
Genetically engineered haemopoietic growth factors are expected to have an increasing 
impact on the use of allogeneic blood components. These should only be used by 
clinicians with relevant expertise.
Recombinant Human Erythropoietin (r-HuEPO)
■  
Epoetin alfa - Eprex®, Binocrit®
■  
Epoetin beta - NeoRecormon® 
Administration of r-HuEPO can increase the rate of red cell production, principally 
through its proliferative effect on erythroid precursors.
The use of r-HuEPO in patients with chronic renal failure has seen a significant reduction 
in the requirement for repeated transfusion of red cells, allowing them to live virtually 
transfusion-free and without symptomatic anemia. The benefit is seen prior to dialysis 
and in dialysis-dependent patients. For patients awaiting renal transplantation, reducing 
allogeneic red cell exposure may reduce the risk of adverse outcomes from immune 
modulation and/or transfusional hemosiderosis.
Patients experiencing chronic anaemia with reduced levels of circulating erythropoietin 
may require fewer red cell transfusions if treated with r-HuEPO. They include those with:
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■  
chronic inflammatory diseases such as rheumatoid arthritis
■  
cancer, with or without chemotherapy treatment
■  
myelodysplastic syndromes
There is evidence that the use of r-HuEPO along with iron supplements can reduce 
transfusion requirements for anaemia of prematurity seen in infants with very low 
birthweight (< 1000 g). However, studies have shown that the benefits are only seen 
when treatment with r-HuEPO is initiated after two to four (or more) weeks of life. 
Before this, the major factor affecting transfusion requirements for sick neonates is 
iatrogenic blood loss, for which treatment with r-HuEPO is ineffective.
Eprex® and Binocrit® have the following indications: 
■  
Severe symptomatic anaemia of renal origin in patients with renal insufficiency 
not yet undergoing dialysis.
■  
Anaemia associated with chronic renal failure in paediatric and adult patients 
on dialysis.
■  
Chemotherapy-induced anaemia in patients with non-myeloid malignancies.
■  
Adult patients with mild-to-moderate anaemia (haemoglobin 100 - 130 g/L) 
scheduled for elective surgery with an expected moderate blood loss (i.e., 2 - 4 
units or 900 - 1800 mL), to reduce exposure to allogeneic blood transfusion 
and to facilitate erythropoietic recovery.
■  
To augment autologous blood collection in anaemic adult patients undergoing 
major surgery who are not expected to deposit preoperatively their complete 
perioperative blood needs.
Granulocyte-Colony Stimulating Factor (G-CSF)
■  
Filgrastim - Zarzio®, Neupogen® 
■  
Pegfilgrastim - Neulastim®
G-CSF is accepted therapy in the management of patients with severe neutropenia 
associated with chemotherapy-induced bone marrow failure, autoimmune and drug-
induced disorders, congenital agranulocytosis and to increase the level of haemopoietic 
progenitor cells (HPC) in the circulation prior to collection by apheresis for autologous 
and allogeneic HPC transplantation.
CXCR4 Chemokine Receptor Antagonist
■  
Plerixafor - Mozobil®
Plerixafor, an antagonist of the CXCR4 chemokine receptor, is used in combination 
with G-CSF to enhance mobilisation of haematopoietic stem cells in adult patients 
with myeloma and lymphoma whose cells mobilise poorly. 
Thrombopoietin Receptor Agonist 
■  
Eltrombopag olamine - Revolade® 
Eltrombopag binds to the thrombopoietin receptor (TPO-R) inducing proliferation and 
differentiation of megakaryocytes with subsequent platelet production. Revolade® is 
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indicated for the treatment of adult patients with chronic immune thrombocytopenic 
purpura (ITP) refractory to corticosteroids and immunoglobulins, and for the treatment 
of thrombocytopenia in patients with chronic hepatitis C to allow the initiation and 
maintenance of interferon-based therapy. Promising results following the use of 
eltrombopag in other clinical areas including myelodysplasia, severe aplastic anaemia 
refractory to immunosuppressive therapy, non-myeloablative chemotherapy and 
thrombocytopenia due to HIV and liver disease are the subject of ongoing research.
8.5 
Recombinant Coagulation Factors 
These products should only be used by clinicians with relevant expertise.
Recombinant Factor VIII (rFVIII)
■  
Moroctocog alfa -  Xyntha®
■  
Octocog alfa - Kogenate® FS, Advate, Recombinate™
rFVIII has similar efficacy to plasma-derived factor VIII in the management of bleeding 
and a similar rate of development of inhibitors associated with deficiency of circulating 
factor VIII (haemophilia A). It contains no von Willebrand factor (vWF) and therefore 
should not be used for improving haemostasis in von Willebrand disease (vWD). Unlike 
other rFVIII products, Recombinate™ contains human albumin, added to stabilise the 
factor VIII and therefore could theoretically transmit blood-borne infections. 
Recombinant Factor IX (rFIX)
■  
Nonacog alfa - BeneFIX®
■  
Nonacog gamma - Rixubis
■  
Eftrenonacog alfa - Alprolix 
rFIX has similar efficacy to plasma-derived factor IX in the management of bleeding 
and a similar rate of development of inhibitors associated with deficiency of circulating 
factor IX (haemophilia B, Christmas Disease). No human protein is added to stabilise 
the product.
Recombinant Factor VIIa (rFVIIa)
■  
Eptacog alfa - NovoSeven® RT 
NovoSeven® RT is licensed for the treatment of bleeding episodes in patients with 
haemophilia A or B who have inhibitors to factors VIII and IX respectively, in patients 
with congenital factor VII deficiency and in patients with Glanzmann’s thrombasthenia 
refractory to platelet transfusion due to GPIIb-IIIa and/or HLA antibodies. 
8.6 
Desmopressin acetate (Octostim®, Minirin®)
Desmopressin should only be used by clinicians with relevant expertise. It is a synthetic 
analogue of the antidiuretic hormone vasopressin. When administered in high doses of 
0.3 mcg/kg it releases factor VIII (FVIII) and von Willebrand factor (vWF) from endothelial 
storage sites with a three to five-fold rise in plasma FVIII coagulant activity (FVIII:C) and 
a three to four-fold rise in vWF level. Desmopressin has also been shown to lead to 
improvement in, or normalisation of, assays of platelet function, including the bleeding 
time, in patients with uremia, liver cirrhosis, congenital or substance-induced platelet 
dysfunction. The effect of desmopressin on FVIII:C lasts for six to eight hours while 
the effect on bleeding time is for a shorter period of one to three hours. 
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Indications for use
■  
Mild to moderate Haemophilia A
■  
von Willebrand disease (vWD)
 
-   In most patients with type I vWD administration of desmopressin will increase 
von Willebrand factor-antigen (vWF:Ag) level three to four-fold and shorten 
or normalises the bleeding time. 
 
-   Some but not all type IIA vWD patients respond to desmopressin.
 
-   In type IIB vWD administration of desmopressin is generally contraindicated 
as it fails to shorten the bleeding time and may produce a severe transient 
thrombocytopenia.
 
-   Desmopressin is also contraindicated in pseudo von Willebrand’s disease.
 
-   Type III vWD does not respond to desmopressin.
■  
Congenital platelet function defects
■  
Acquired platelet function defects
■  
Uraemia
■  
Hepatic cirrhosis
Contraindications
■  
Habitual and psychogenic polydipsia
■  
Unstable angina, myocardial infarction or stroke 
■  
Decompensated cardiac failure
■  
Type IIB von Willebrand’s disease
Precautions
■  
Hyponatraemia; with repeated doses, fluid restriction and monitoring of sodium 
levels are recommended
■  
Patients at risk for raised intracranial pressure, including closed head injury
■  
Caution when using in children under 2 years of age
■  
Caution when using in patients > 70 years of age, especially those with a history 
of vascular disease
Presentation
The product is presented as 1 mL ampoules containing 15 mcg (Octostim®) or 4 
mcg (Minirin®) of desmopressin acetate. Administration is either by intravenous or 
subcutaneous injection. A suitable intranasal preparation is not currently available in 
New Zealand.
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Dosage and administration
Desmopressin acetate 0.3 mcg/kg for intravenous administration can be diluted in 
50 - 100 mL of isotonic saline and given no more than one hour before surgery. The 
first 5 mL is given over five minutes and, provided the patient does not show marked 
tachycardia or other adverse reactions, the remainder of the dose may be given over 
the next 15 - 30 minutes. When administered subcutaneously, Octostim® should be 
given one hour preoperatively. 
If a positive effect is obtained, the initial dose may, if necessary, be repeated once after 
24 hours, with sodium monitoring and fluid restriction, and no more than two doses in 
any five day period. Octostim® given subcutaneously and once daily is the preferred 
method to achieve adequate release of FVIII and vWF while minimising side effects. 
Patients may become progressively unresponsive to desmopressin with repeated 
daily doses over two to three days. Responsiveness will return when the drug has 
been discontinued for two days. For this reason it is not recommended to perform a 
desmopressin trial within four days of planned surgery.
8.7 
Tranexamic Acid (Cyklokapron®)
Tranexamic acid is an inhibitor of fibrinolysis. Initially this compound was used primarily 
to reduce mucosal bleeding in patients with haemophilia and von Willebrand disease. 
Currently it is also used to decrease blood loss in cardiopulmonary bypass and joint 
surgery, trauma-related bleeding, obstetric complications, severe hypoproliferative 
thrombocytopenia, disorders of platelet dysfunction (e.g., Glanzmann’s thrombasthenia), 
following treatment with anti-platelet medications and in conditions associated with 
increased fibrinolysis including menorrhagia, prostatectomy, cervical conisation, 
gastrointestinal bleeding, dental extraction and epistaxis. Additionally, tranexamic acid 
has a role in the management of hereditary angioedema.
Use of tranexamic acid carries a risk of clot formation resistant to fibrinolytic therapy 
and is therefore generally contraindicated in thromboembolic disease and in DIC. Due 
to the risk of clot-induced hydronephrosis, tranexamic acid is contraindicated with 
haematuria/bleeding from renal parenchyma.
Dose adjustment is required with even mild renal impairment.
Presentation
Cyklokapron® is presented as 500mg oral tablets or 5 mL ampoules containing 500 
mg tranexamic acid. Administration of the latter is either by IV injection or, in the case 
of epistaxis or dental surgery, topical via application of soaked gauze. 
Dosage and administration
The recommended standard dose of tranexamic acid is 1000 - 1500 mg orally or 
500 - 1000 mg IV at a rate of 1 mL/minute, two to three times per day. In general, 
the use of tranexamic acid intravenously is recommended only when adequate doses 
cannot be administered orally.
In the setting of surgery, tranexamic acid 10 - 15 mg/kg administered IV over 10 
minutes may be given as preoperative prophylaxis or as therapy for bleeding. Further 
intravenous infusion or bolus IV doses of 500 - 1000 mg, every 8 hours, may be given. 
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Oral doses up to 1500 mg, administered three to four times daily, may be used for up 
to 14 days to cover the post-operative period. 
For trauma-related bleeding, tranexamic acid should be initiated within 3 hours of 
the event.
For oral mucosal bleeding, experience suggests clinical effect can be achieved from 
the use of a crude mouth wash made by dispersing 500 mg tranexamic acid tablet 
to a slurry in 10 - 15 mL water and swirling the total preparation around the mouth 
for two minutes before expelling. This is used four times daily for up to seven days.
8.8 
Iron Supplementation
Preoperative identification and treatment of iron deficiency anaemia may avoid pre- and/
or post-operative red cell transfusion in elective surgery. Correction of iron deficiency, 
even in the absence of anaemia, may improve erythropoietic recovery and reduce 
the risk for red cell transfusion in post-operative patients. Where red cell transfusion 
is required (e.g., for cardiac compromise), iron therapy should always follow, as 
transfusion fails to replenish deficient iron stores. 
The following algorithm is adapted from the Australian National Blood Authority (NBA) 
Preoperative Haemoglobin Assessment and Optimisation Template 
of the Perioperative 
(2012) Patient Blood Management Guidelines.
    
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9
OTHER SERVICES PROVIDED BY NZBS
9.1 
Therapeutic Apheresis
Some NZBS centres provide therapeutic apheresis programmes using a centrifugal 
cell separator. Procedures may be carried out in a hospital ward or, if there is a medical 
officer on site and patients are mobile and in good health, at a NZBS blood centre.
Therapeutic plasma exchange (TPE) is an established first-line treatment in some 
conditions and second-line treatment in several others. TPE may be combined 
with other medical therapy in managing diverse conditions such as hyperviscosity 
syndromes, Guillain-Barré syndrome, thrombotic thrombocytopenic purpura, chronic 
inflammatory demyelinating polyneuropathy, familial hypercholesterolaemia and renal 
transplant rejection. It is also sometimes used for the treatment of myasthenia gravis, 
polymyositis, SLE and other autoimmune disorders. The potential hazards of plasma 
exchange should be taken into account when considering this treatment.
Leucopheresis may be used to reduce leucostasis in patients with very high white 
cell counts. Similarly, plateletpheresis may occasionally be used for patients with 
complications due to thrombocytosis.
Replacement fluids used for TPE usually include albumin or fresh frozen plasma (FFP). 
Saline, usually in combination with albumin, can also be used in certain conditions 
such as hyperleucocytosis and thrombocytosis. FFP is occasionally used to correct a 
deficiency of coagulation factors and cryosupernatant may be used for patients with 
thrombotic thrombocytopenic purpura. 
Complications of therapeutic apheresis include allergic reactions to FFP or 
cryosupernatant, volume overload or hypovolaemia, air embolism, haemolysis, 
extracorporeal clotting, citrate toxicity, coagulopathy and vasovagal attacks. However, 
present procedural methods appear to minimise these complications.
To request therapeutic apheresis, contact a NZBS Transfusion Medicine Specialist/
Medical Officer.
9.2 
Therapeutic Venesection
Whole blood therapeutic venesection is available for patients with medical conditions 
where regular venesection is beneficial such as haemochromatosis, polycythaemia 
and porphyria cutanea tarda. 
Blood collected from an individual with genetic haemochromatosis may potentially 
be used to prepare therapeutic blood components and fractionated products if the 
patient meets all normal donor selection criteria and is registered as a blood donor. 
See Section 2.7: Haemochromatosis for further information.
In the case of polycythaemia vera managed by venesection in combination with 
cytoreductive medication, the referring doctor remains responsible for the management 
of the patient’s underlying condition and should regularly review the patient (at least 
every 12 weeks), as well as providing instructions concerning the frequency of 
venesection. NZBS is responsible for the venesection collection and for ensuring the 
safety of the patient during the procedure. For patients with polycythaemia managed 
by venesection alone, and following clear instruction from the referring doctor, it may be 
Page 162 
Transfusion Medicine Handbook 3rd Edition

possible for NZBS to monitor the haematocrit and adjust the frequency of venesection 
accordingly. In such cases, review by the referring doctor at intervals greater than 12 
weeks may be appropriate.
A similar arrangement for the monitoring of ferritin levels and titration of therapeutic 
venesection may be made for patients with porphyria cutanea tarda.
9.3 
Tissue Bank
The NZBS Tissue Banks provide:
■  
Cadaver split skin, sourced locally and from international tissue banks, used as 
a physiological dressing to treat victims of burns.
■  
Donated or autologous bone, mostly femoral heads, used in reconstructive 
orthopaedic surgery.
■  
Autologous cranial bone flaps held for neurosurgical patients until reimplantation 
weeks to months later.
NZBS Tissue Banks are located in the NZBS centres in Auckland, Hamilton, Palmerston 
North, Wellington, Christchurch and Dunedin. Cadaver skin is only available from the 
Auckland centre. Donated bone is held at the NZBS sites as well as a number of 
DHB-managed blood banks. 
All donations are voluntary. Written consent is required from the donor or, in the case 
of skin, from next of kin. All donations are tested for infectious diseases and bacterial 
contamination. Frozen tissue is generally stored frozen and held for up to five years.
All tissue is issued frozen to a named patient and is only for that patient. An information 
sheet is available from Tissue Bank for consenting patients. Unused frozen tissue 
should be returned to the Tissue Bank. Unused thawed tissue must be discarded.
9.4 
Autologous Serum Eye Drops
Autologous serum eye drops (SED), a blood component prepared by NZBS, is used 
for treating dry eyes and corneal epithelial defects. It is not normally first-line treatment 
due to the cost and requirement that patients donate blood. However, in selected 
patients, SED have proven to be a successful treatment modality.
Conditions for which SED can be used include severe Sjögren’s syndrome, Stevens-
Johnson syndrome, ocular cicatricial pemphigoid, some causes of epithelial limbal 
stem cell deficiency such as chemical or thermal ocular surface burns and other 
severe ocular surface disorders that do not respond to conventional therapies. SED 
may also be useful in acute management of severe sight threatening ocular surface 
chemical or thermal burns.
Although not fully defined, it is believed that epidermal growth factor, transforming 
growth factor ß, vitamin A, platelet-derived growth factor and fibronectin are important 
serum constituents that promote healing of the ocular surface. 
SED is prepared from a single blood donation and contains no added preservatives 
or antimicrobial agents. It has the potential to transmit infectious diseases or become 
contaminated with microorganisms. Accordingly, blood collected for SED must meet 
Transfusion Medicine Handbook 3rd Edition 
Page 163

standard safety requirements. This includes a donor health assessment and screening 
of the blood donation to exclude evidence of human immunodeficiency virus, hepatitis 
B virus and hepatitis C virus. Following manufacture of SED, a proportion of the eye 
drop bottles are cultured for 14 days to confirm bacterial sterility.
To access the service, ophthalmologists complete a specific request form that is 
forwarded to NZBS. As this constitutes a prescription, it is valid for three months 
only, as per the Medicines Act, although blood is only collected every six months. 
Due to the time required for manufacturing and sterility testing, 18 working days are 
normally required from donation to issuing of SED. In exceptional circumstances and 
with the patient’s consent, the ophthalmologist may request that SED are issued prior 
to completion of the sterility testing. 
Appropriate storage of SED vials is essential to minimise the risk of bacterial 
contamination. Vials are stored frozen in a NZBS facility or hospital blood bank and 
are dispensed in quantities necessary to cover a 4 week period. The dispensed vials 
should be kept frozen until needed, usually in the patient’s domestic freezer. Each 
vial usually lasts one week and should be stored in a refrigerator once thawed. Any 
adverse events should be reported to NZBS for investigation.
For patients where blood cannot safely be donated or where allogeneic SED are the 
preferred product, for example in ligneous conjunctivitis, NZBS can, on a named 
patient basis, prepare SED from an allogeneic donation. NZBS does not hold this 
as a stock item. 
9.5 
Reference Laboratory (Immunohaematology)
The NZBS Reference Laboratory is located in the NZBS Auckland centre and offers a 
national immunohaematology testing service as well as clinical and technical advice for 
resolving problems encountered during pretransfusion and antenatal testing such as:
■  
blood grouping, antibody screening and crossmatching
■  
antibody identification/confirmation and resolution of difficult antibody mixtures
■  
antibody titration (antenatal, cold agglutinins and isoagglutinins)
■  
adsorption and elution studies for patients with autoantibodies
■  
red cell phenotyping and genotyping
9.6 
Tissue Typing Laboratory
The NZBS Tissue Typing Laboratory is also located in the NZBS Auckland centre and 
is responsible for tissue typing tests in support of New Zealand’s bone marrow and 
solid organ transplant programmes. The laboratory also carries out testing for disease 
association markers, for antibodies implicated in transfusion-related reactions, for 
antibodies against platelet antigens and is responsible for the provision of compatible 
or matched platelets for transfusion.
The following provides an indication of the wide range of white cell and platelet-related 
investigations undertaken:
■  
HLA Class I and Class II typing
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Transfusion Medicine Handbook 3rd Edition

■  
HLA-antibody screening
■  
T- and B-lymphocyte crossmatching
■  
platelet-associated antibody testing
■  
serum platelet antibody testing 
■  
platelet crossmatching
■  
fetal and neonatal alloimmune thrombocytopenia (FNAIT) investigation
■  
platelet genotyping
Transfusion Medicine Handbook 3rd Edition 
Page 165

10
NZBS SAMPLE REQUIREMENTS
It is not possible to overemphasise the importance of proper patient identification. 
Most errors relating to transfusion practice arise from administrative and clerical error. 
These errors can have serious consequences for patients and are sometimes fatal.
Collection and labelling of blood samples for pretransfusion testing is described in 
Section 3.6: Collecting Blood Samples for Pretransfusion Testing.
The sample acceptance criteria used by NZBS are based on the 2016 Australian & 
New Zealand Society of Blood Transfusion (ANZSBT) Guidelines for Transfusion, Pre 
and Postnatal Immunohaematology Testing
. Blood Bank staff are not authorised to 
accept samples which do not meet labelling requirements. Where necessary these 
will be rejected and new samples requested. Where a dispute arises in relation to a 
sample, the final decision on suitability for testing will lie with an NZBS Transfusion 
Medicine Specialist/Medical Officer.
The following tables provide a brief guide to the types of samples NZBS requires 
for laboratory investigations. Specific guidance can be obtained from the individual 
laboratories and NZBS Transfusion Medicine or Nurse Specialists.
Page 166 
Transfusion Medicine Handbook 3rd Edition

op
Tube T
Pink
Pink
Pink 
Pink
Pink
N/A
Pink
om transfused unit(s)
ed
e-transfusion sample
2 A

A
A pr
A post-transfusion sample

emnants fr
Sample Requir
1 x 6 mL EDT
1 x 6 mL EDT
1 x 6 mL EDT
1 x 6 mL EDT
1 x 6 mL EDT
Giving set/r
2 x 6 mL EDT

oup & 
equir
ovision 
etransfusion 
ovision of blood
, not fractionated 
1
een in pr
esting
e antibody identification 
equir
een’
oducts
esence of autoantibodies may r
Comment
Normally performed as part of a ‘Gr
Scr
A positive antibody scr
testing will r
which may delay the pr
Reactions observed with transfusion of 
blood components only
pr
Pr
adsorption techniques to detect underlying 
alloantibodies which may delay pr
of blood
ransfusion Medicine Specialist for specific sample requirements or if further information is required.
oup
eaction investigation
  Samples Required for Pretransfusion T
een
oup & scr
Table 10.1:
Test 
ABO / RhD gr
Gr
Red cell antibody identification
Transfusion r
Autoimmune haemolytic anaemia
Contact the Blood Bank or T
Ethylenediaminetetraacetic acid.
1
2
Transfusion Medicine Handbook 3rd Edition 
Page 167

op
Tube T
Pink
Pink
Pink or lavender
Pink or lavender
Pink

 EDT2

ed

A

Sample Requir
1 x 6 mL EDT
1 x 6 mL EDT
1 x 6 mL or 4 mL EDT
1 x 6 mL or 4 mL or 0.5 mL
1 x 6 mL EDT
1
nal blood contamination
esting
.
Comment
Tested for mater
Maintain and transport samples at 37°C
 
T)
ransfusion Medicine Specialist for specific sample requirements or if further information is required.
d blood 
een and titration
eening
T on cor
oup & DA
ect antiglobulin test (DA
Table 10.2: Samples Required for Diagnostic T
Test 
Antenatal scr
Antenatal antibody titration
Gr
sample 
Dir
Cold agglutinin scr
Contact the Blood Bank or T
0.5 mL pink top microcontainer for use in infants only
1
2
Page 168 
Transfusion Medicine Handbook 3rd Edition

op
Tube T
Pink
Pink
Pink 
Pink 
Pink
Pink
N/A
Pink
Pink 
Pink or lavender
Pink
om transfused unit(s)

ed
e-transfusion sample
A
A
A
A
A pr
A post-transfusion sample
A
A
A
emnants fr
Sample Requir
2 x 6 mL EDT
1 x 6 mL EDT
1 x 6 mL EDT
2 x 6 mL EDT
1 x 6 mL EDT
1 x 6 mL EDT
Giving set/r
1 x 6 mL EDT
1 x 6 mL EDT
1 x 6 mL or 4 mL EDT
1 x 6 mL EDT
1
esting
y Diagnostic T
d blood sample
egnancies beyond 16 weeks
Comment
Pr
Cor
ransfusion Medicine Specialist for specific sample requirements or if further information is required.
nal 
 4
y or T
oblem
T
om mater
ransfusion Medicine Specialist required
ouping pr
eaction investigation
5
n
 with positive DA2
3
nal phenotyping: HDFN
Table 10.3: Samples Required for Reference Laborator
Test 
Alloantibody investigation
ABO / Rh gr
Extended RBC phenotype
AIHA
Transfusion r
Compatibility testing 
Fetal D genotyping fr
blood
Haemolytic disease of the 
newbor
Pater
and FNAIT
Contact the Reference Laborator
Autoimmune haemolytic anaemia.
Prior discussion with T
Haemolytic disease of the fetus and newborn.
Fetal and neonatal alloimmune thrombocytopaenia.
1
2
3
4
5
Transfusion Medicine Handbook 3rd Edition 
Page 169

op
Tube T
Yellow
Red
Pink
Yellow
Red
Red
Yellow
Red
Pink
Yellow
Red
Yellow
Yellow
Red
Red
Yellow
A tubes.
2
ed
3
A
A
Sample Requir
4 x 10 mL CPDA
1 x 10 mL clotted
1 x 6 mL EDT
1 x 10mL CPDA
1 x 10mL clotted
1 x 10mL clotted
4 x 10 mL CPDA
1 x 10 mL clotted
1 x 6 mL EDT
4 x 10 mL CPDA
1 x 10 mL clotted
1 x 10mL CPDA
4 x 10 mL CPDA
2 x 10 mL clotted
2 x 10 mL clotted
2 x 10 mL CPDA
A samples may alternatively be sent in 7 mL lavender EDT
enal transplant
1 y
ogenitor cell (HPC) or solid 
esis platelet donor
yping Laborator
colepsy
issue T
Comment
Haematopoietic pr organ transplant patient or potential donor  and apher
e.g., ankylosing spondylitis, coeliac disease,  nar
HLA antibodies
Patients awaiting cadaveric r
Solid organ transplant patient or potential  donor
Platelet and platelet-associated antibody
Donor 
Patient
ransfusion Medicine Specialist for specific sample requirements or if further information is required.
y or T
een / 
A) genotyping 
een 
yping Laborator
ossmatch
issue T
efractory to platelets
ossmatch
Table 10.4: Samples Required for T
Test 
HLA typing
(initial or confirmatory)
Disease association
Monthly serum tray 
HLA antibody scr
Lymphocyte cr
Platelet antibody scr cr
Platelet antigen (HP
Patients r
TRALI  investigation
Contact the T
Clotted samples may alternatively be sent in 3 x 5 mL or 2 x 7 mL red top tubes. EDT
Citrate phosphate dextrose adenine.
1
2
3
Page 170 
Transfusion Medicine Handbook 3rd Edition

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