Appropriate Clinical Use of Blood

(ACUB)
Physician’s Handbook

Ministry of Health and Population

Second Edition
Egypt – 2006
All rights reserved. No part of this Handbook may be reproduced
without written permission from the editors.
 General Aim

T he aim of this Handbook is to provide guidance for practitioners of

transfusion medicine, clinicians, and blood bank physicians. Proper
application of the guidelines presented in this book should improve the
quality of medical care for patients requiring blood transfusion.

We appreciate readers’ feedback regarding the quality and content of

this Handbook. We hope to satisfy our readers and welcome any
suggestions to improve future editions of this Handbook.

Please contact us:

Address: 51 Wizaret El Zeraa’ St., Agouza, Giza.
Telephone: (+202) 761-3119 - 748-5341
Fax: (+202) 761-3124
Website: www.nbtsegypt.org

i
 Preface

I n Egypt, over one million units of blood donations are required

for transfusions every year. Without a sufficient supply of this
life saving resource, many patients would suffer, or die.

The National Blood Transfusion Service (NBTS) shall: (1)

collect blood from voluntary non-remunerated donors; (2) screen
all donated blood for infectious diseases; and (3) issue blood
products to hospitals, according to international standards of
Appropriate Clinical Use of Blood (ACUB).

In order to provide an adequate, safe and effective supply of

blood products, the Swiss State Secretariat for Economic Affairs
(seco) and Egypt’s Ministry of Health and Population (MoHP)
have cooperated for several years to establish a customized,
modern blood transfusion service in Egypt. The Swiss Red Cross
(SRC) has seco’s mandate to assist MoHP in the implementation of
the program “Restructuring the Blood Transfusion Services of the
MoHP”. The program – currently in the second phase of
implementation – aims to centralize all blood transfusion activities
into a single network of blood transfusion centers. The network
acts as sole provider of blood products in Egypt.

The interface between NBTS and physicians – the users of

blood products – is a central part of the program. The ACUB
Physician’s Handbook was therefore developed with the close
cooperation of a team of eminent international and Egyptian
physicians. The Handbook, based on WHO Guidelines for ACUB,
has been customized to meet Egypt’s specific needs. The joint
action of physicians and the NBTS in the application of ACUB is
of utmost importance for the safe and efficient use of blood
products in Egypt. It will also lead to the rationalization of blood
use by eliminating unnecessary transfusions.

ii
 The ACUB Physician’s Handbook ensures that providers and
users of blood products share the same concepts and work together
closely in the area of ACUB. It aims to provide physicians in
different medical fields with state-of-the-art information on
ACUB. Its handy size means it is easy to use in day-to-day work.

This Handbook is divided into two parts. Part I focuses on

available blood components, blood alternatives and related
services. Part II defines guidelines for transfusion medicine in
different clinical areas in order to ensure a safe, efficient and
rational use of blood.

This Handbook will be updated periodically to ensure the

continuity of the state-of-the-art ACUB knowledge and the
adoption of new emerging issues and subjects.

iii
 Introduction

B lood transfusion is an essential part of modern health care.

When performed correctly, it saves lives or rapidly improves
serious clinical conditions.

However, blood transfusion carries a potential risk of

immediate or delayed complications and transfusion-transmitted
infections. Blood should only be prescribed to treat conditions
associated with significant morbidity or mortality that cannot be
prevented or managed by other means. Thus it is always essential
to compare the risks of transfusion versus the benefits to the
patient. The benefits should always outweigh the risks.

On the other hand, blood is a scarce human resource as it is

obtained voluntarily from blood donors. Ensuring safety and
clinical effectiveness of blood through accurate, quality-controlled
testing and processing requires significant investments – both
human and financial.

It is of utmost importance to formulate and adopt a National

Blood Policy covering all aspects of Blood Transfusion Services
(BTS), and to create standards for every step in the transfusion
process.

Also, both BTS and clinical users should combine efforts to

establish and implement policies and strategies aimed at reducing
the need for transfusions while minimizing unnecessary
transfusions and ensuring the safe, rational and appropriate use of
blood and blood components.

iv
 These strategies include:
• Prevention, early diagnosis and effective treatment of conditions
that could result in the need for transfusion, e.g. treatment of
anemia.
• Use of good surgical and anesthetic techniques, e.g. epidural
anesthesia.
• Pharmaceutical products to reduce surgical blood loss, e.g.
antifibrinolytic agents.
• Availability and use of alternatives for volume replacement, i.e. IV
replacement fluids such as crystalloids and colloids.
• Appropriate prescribing of blood and blood components according
to the guidelines mentioned in this Handbook.
• Safe pre-transfusion procedures, i.e. blood grouping identification,
crossmatching and antibody screening and identification.
• Safe administration of blood and blood components, i.e. applying
good clinical transfusion practices including handling of blood and
close monitoring of the transfused patient.
• Quality system for the BTS, Hospital Blood Banks (HBBs) and all
clinical departments involved in transfusion. This system will
include Standard Operating Procedures (SOPs) for all steps of the
transfusion process, and a documentation system for recording
these steps from donor to patient.
• System to monitor adverse events and errors related to transfusion
(hemovigilance) and clinical audit.

v
TABLE OF ABBREVIATIONS
Ab Antibody
ACS American College of Surgeons
ACUB Appropriate Clinical Use of Blood
ADH Anti-Diuretic Hormone
Ag Antigen(s)
AIDS Acquired Immunodeficiency Syndrome
APTT Activated Partial Thromboplastin Time
ATP Adenosine Triphosphate
BP Blood Pressure
BT Bleeding Time
BTS Blood Transfusion Service
BV Blood Volume
CBC Complete Blood Count
CDP Cryo Depleted Plasma
CLL Chronic Lymphatic Leukemia
CMV Cytomegalovirus
CPDA-1 Citrate Phosphate Dextrose Adenine
CVP Central Venous Pressure
DDAVP Desmopressinum. 1-(3 Mercaptopropionic Acid) – 8-D-Arginine Vasopressin
DIC Disseminated Intravascular Coagulopathy
EACA Epsilon Amino Caproic Acid
EBV Epstein-Barr Virus
ECG Electrocardiogram
ELISA Enzyme Linked Immunosorbent Assay
EPO Erythropoietin
FDP Fibrin Degradation Product
FFP Fresh Frozen Plasma
FNH(T)R Febrile Non-Hemolytic (Transfusion) Reaction
G CSF Granulocyte Colony Stimulating Factor
GIT Gastrointestinal Tract
GM CSF Granulocyte Macrophage Colony Stimulating Factor
GvHD Graft Versus Host Disease
Gy Grey
G6PD Glucose 6 Phosphate Dehydrogenase
Hb Hemoglobin
HBB Hospital Blood Bank
Hct Hematocrit
HDN Hemolytic Disease of the Newborn
HLA Human Leucocyte Antigen
HHV-8 Human Herpe Virus type 8
HR Heart Rate
HTC Hospital Transfusion Committee
HTLV Human T Lymphocyte Virus
HUS Hemolytic Uremic Syndrome
ICU Intensive Care Unit
Ig Immunoglobulin

vi
IM Intramuscular(ly)
INR International Normalized Ratio
IU International Unit(s)
IV Intravenous(ly)
KCl Potassium Chloride
LDH Lactic Dehydrogenase
MSBOS Maximum Surgical Blood Ordering Schedule
NaCl Sodium Chloride
NaHCO3 Sodium Bicarbonate
NAIT Neonatal Alloimmune Thrombocytopenia
NBTS National Blood Transfusion Service
NSAID Non-Steroidal Anti-Inflammatory Drug
Ob/Gyn Obstetrics And Gynecology
PLA-1a Platelet Antigen – 1a
PLT Platelet
PPH Primary Postpartum Hemorrhage
PRC Packed Red Cell
PT Prothrombin Time
PTT Partial Thromboplastin Time
Q Cardiac Output
RA Refractory Anemia
RARS Refractory Anemia With Ring Sideroblasts
RBC Red Blood Cell
RBTC Regional Blood Transfusion Center
RCT Randomized Controlled Trial
RDP Random Donor Platelet
RDS Respiratory Distress Syndrome.
r Hu Epo Recombinant Human Erythropoietin
RV Resuscitation Volume
SAGM Saline Adenine Glucose Mannitol
SC Subcutaneous(ly)
SD Standard Deviation
SDP Single Donor Platelet
seco State Secretariat For Economic Affairs
SLE Systemic Lupus Erythematosis
SOP Standard Operating Procedure
SV Stroke Volume
TPO Thrombopoietin
TRALI Transfusion-Related Lung Injury
TT Thrombin Time
TTI Transfusion Transmissible Infection
TTP Thrombotic Thrombocytopenic Purpura
vCJD Virus of Creutzfeld Jacob Disease
VD Volume Deficit
WB Whole Blood
WBC White Blood Cell
WHO World Health Organization
WNV West Nile Virus

vii
LIST OF TABLES

Page
1 Cellular Blood Components 4
2 Non-cellular Blood Components 6
3 Time Needed for Special Processing of Blood Components 12
4 Types of Crystalloids 19
5 Types of Colloids 20
6 Characteristics of the Most Widely Used Pharmaceuticals 22
7 ABO Compatible Blood Components 29
8 Characteristics of WB Stored for 35 Days in CPDA-1 32
9 Time Limits for Infusion of Specific Components 41
10 Guidelines for Recognition and Management of Acute Transfusion
45
Reactions
11 Drugs Used in Acute Transfusion Reactions 49
12 Classification of Anemia according to Hb Level 61
13 Classification of Anemia according to Severity 61
14 Classification of Hypovolemia and Shock in Adults 69
15 Laboratory Investigations: Normal Results 79
16 Dosage of F VIII and Alternatives in the Treatment of Hemophilia A 80
17 Dosage of F IX and Alternatives in the Treatment of Hemophilia B 83
18 Mean Hb Values in Term and Pre-term Neonates and Their Changes
88
during the First Month of Life
19 Normal Blood Indices beyond the Neonatal Period 88
20 Estimated Pediatric Blood Volumes 93
21 Selecting Blood Components for Neonatal Transfusion 95
22 IV Fluids Used in the Neonatal and Pediatric Intensive Care Unit 102
23 Transfusion of Platelet Concentrate in Pediatrics and Neonates 103

viii
LIST OF ANNEXES

1 Prescribing Blood: A Checklist for Clinicians

2 A Sample Blood Request Form
3 A Sample Blood Ordering Schedule
4 A Sample Compatibility Label
5 A Sample Monitoring Sheet for Transfused Patient
6 A Sample Post-transfusion Reaction Investigation Form
7 Algorithm for Massive Transfusion

ix
 List of Contributors (in alphabetical order)

Dr. Amr El Noury Consultant of Ob/Gyn, El-Galaa Hospital, Egypt.

Prof. Brian McClelland Director, Edinburgh and South East Scotland BTS, UK.

Prof. Ezz Eldin Saleh Professor of Anesthesia, El-Menofia University, Egypt.

Dr. Faten Moftah Director General of NBTS, Egypt.

Prof. Galila Mokhtar Professor of Pediatrics, Ain Shams University, Egypt.

Prof. Gheorghe Peltecu Professor of Ob/Gyn, Carol Davila University, Romania.

Dr. Hossam Ammar Consultant of Neonatal ICU, Ain Shams University, Egypt.

Prof. Hossam Kamel Vice-President for Graduate Studies and Research, Cairo University, Egypt.

Dr. Hussein Samy Consultant and Director of ICU, Egypt Air Hospital, Egypt.

Prof. Mahmoud Tarek Professor of Pediatrics, Ain Shams University, Egypt.

Dr. Mervat Doss Technical Manager for ACUB, NBTS, Egypt.

Prof. Omar Fahmy Professor of Medicine, Cairo University, Egypt.

Prof. Salwa Youssef Professor of Clinical Pathology, Ain Shams University, Egypt.

Dr. Sherif Ashoush Lecturer of Ob/Gyn, Ain Shams University, Egypt.

Prof. Tawhida Abdel Ghaffar Professor of Pediatrics, Ain Shams University, Egypt.

x
TABLE OF CONTENTS

General Aim i
Preface ii
Introduction iv
List of Abbreviations vi
List of Tables viii
List of Annexes ix
List of Contributors x

Part I: Blood Transfusion Activities and Blood Banking 1

I.1. Blood Components’ Characteristics 3
I.1.1. Cellular Blood Components 3
I.1.2. Non-cellular Blood Components 3
I.1.3. Special Processing of Blood Components 8
I.2. Plasma Derivatives 13
I.2.1. Human Albumin Solutions 13
I.2.2. Coagulation Factors Concentrate 14
I.2.3. Immunoglobulins (Igs) 15
I.3. Blood Transfusion Alternatives 17
I.3.1. Replacement Fluids 17
I.3.2. Pharmaceuticals 18
I.3.3. Autologous Blood Transfusion 24
I.4. Hospital and Bedside Transfusion Practice 26
I.4.1. Ordering Blood 26

xi
 1.4.2. Blood Ordering Policies 27
I.4.3. Storage and Transportation of Blood Components 31
I.4.4. Handling of Blood Components 34
I.4.5. Administration and Monitoring of Blood Components 39
I.5. Adverse Transfusion Reactions 42
I.5.1. Immediate Complications 42
I.5.2. Delayed Complications 43
I.6. Hospital Transfusion Committee (HTC) 52
I.6.1. Members of the HTC 53
I.6.2. Role of the HTC 54
I.7. Hemovigilance 55
I.8. Therapeutic Apheresis 56

Part II: Clinical Transfusion Practice 59

II.1. Anemia 61
II.1.1. Chronic (Compensated) Anemia 64
II.1.2. Severe (Decompensated) Anemia 64
II.2. Hypovolemia and Massive Transfusion 66
II.3. Coagulation and Bleeding Disorders 74
II.3.1. Disseminated Intravascular Coagulopathy (DIC) 74
II.3.2. Coagulation Disorders and Surgery 76
II.3.3. Bleeding Disorders 78
II.3.3.1. Congenital Bleeding Disorders 80
II.3.3.2. Acquired Bleeding Disorders 84
II.3.3.3. Disorders of Platelets 86

xii
 II.4. Transfusion Practice in Different Clinical Situations 88
II.4.1. Transfusion in Pediatrics and Neonates 88
II.4.1.1. Pediatric Anemia 88
II.4.1.2. Bleeding and Clotting Disorders 94
II.4.1.3. Guidelines for Neonatal Exchange Transfusion 97
II.4.1.4. Specific Clinical Situations 102
II.4.2. Transfusion in Obstetrics 107
II.4.3. Transfusion in GIT and Hepatic Diseases 114
II.4.4. Transfusion in Renal Diseases 116
II.4.5. Transfusion in Transplant Patients 118
II.4.6. Transfusion in Hematological Diseases 119
II.4.6.1. Bone Marrow Failure 119
II.4.6.2. Hereditary Hematological Disorders 119
II.4.7. Transfusion in Surgical Patients 126

Annexes
Glossary of Terms
List of Sources

xiii
xiv
 Part I
Blood Transfusion Activities and Blood Banking

-1-
-2-
 Only blood which has been obtained from appropriately selected donors
and has been screened for transfusion-transmissible infectious agents should
be issued for transfusion, other than in the most exceptional life threatening

Part I: 1.
situations.

Voluntary non-remunerated blood donors from low risk groups who

give blood regularly are the foundation of a safe and adequate blood supply.
A reliance on family replacement and paid blood donors should be phased
out, as these donors are associated with a significantly higher prevalence of
transfusion-transmissible infections.

I.1. Blood Components’ Characteristics

The processing of Whole Blood (WB) into components allows a single
blood donation to provide treatment for 2 or 3 patients while avoiding the
transfusion of elements of the WB that the patient might not require. It also
ensures optimum storage conditions and temperatures for each blood
component. Blood components include cellular components and non-
cellular components.

I.1.1. Cellular Blood Components (Table 1):

1. Whole Blood (WB).
2. Packed Red Cells (PRCs).
3. Platelet Concentrate.
4. Granulocytes.

I.1.2. Non-cellular Blood Components (Table 2):

1. Plasma, as Fresh Frozen Plasma (FFP), Liquid Plasma and Frozen
Plasma.
2. Cryoprecipitate.
3. Cryodepleted Plasma (CDP).

-3-
 Table 1: Cellular Blood Components
Component Volume Contents Indication Contraindications Dose and Administration
WB 1 pack= • Plasma Red cell Risk of volume • 1 pack raises Hb by l g/dl in
450 ml ± • RBCs replacement in overload in patients an adult
50 ml • WBCs acute blood loss with: • Transfusion should be
• Anticoagulant/ with hypovolemia • Chronic anemia started within 30 min. of
Fresh WB preservative • Exchange • Incipient heart issuing and completed
(< 7 days old) solution (63 transfusion and failure within 4 hours of starting
ml) massive • Old age transfusion
• No functional transfusion in • Medication should never be
platelets neonates added to a unit of blood
• No labile • Advanced renal • Crossmatching is essential
clotting failure with prior to transfusion
factors (V and hyperkalemia
VIII) and acidosis
• Hct: 37-39%
-4-

PRCs 150-250 • RBCs • Decompensated As WB (additional 70-100 ml

ml/pack • Reduced anemia (to of 0.9% saline using Y-shaped
plasma increase red cell tube to improve transfusion is
• WBCs mass) in optional to reach a Hct of 50-
• Platelets (non- normovolemic 70%
functioning) patients and
• Hct: 60-75% patients at risk
of volume
overload
• Used with
replacement
fluids in acute
blood loss
 Table 1: Cellular Blood Components (Continued)
Component Volume Contents Indication Contraindications Dose and Administration
Platelet 50-60 ml • Platelets: To stop bleeding • ITP • Dose: 1 RDP unit/10 kg
Concentrate minimum of due to: • TTP • 1 unit of RDPs raises the
(35 x109) platelet count by ≈ 5-10 x
• Thrombocyto-
A. Random • Leucocytes penia 109/l
Donor (0.2 x109) • In a 70 kg patient, 4-6 packs
• Platelet function
Platelets • RBCs (<1.2 x defects of RDPs should raise platelet
(RDPs) Single 109) count by ≈ 20-40 x 109/l
• Prevention of
Unit • pH at the end bleeding in • Should be administered as
of shelf life is surgical patients soon as possible within
6.8 -7.4 with severe pre- 4 hours of pooling
B. RDP Pool 250-300 • Platelets operative • Administered through a
of 5 units ml ≈ (150-500 x platelet standard blood transfusion set
109) deficiency <50 x • Must not be refrigerated
109/l before infusion
-5-

• Should be transfused over 30-

60 min (for handling of
platelets see I.4.3.)
• Crossmatching is not essential
prior to transfusion, give
ABO compatible platelets
C. Single 150-300 • Platelets • 1 therapeutic dose = 4-8 RDP
Donor ml/pack ≈ (150-500 x packs
Platelets 109) • 1 therapeutic dose raises
(SDPs) • Leucocytes platelet count by ≈ 30-60 x
Apheresis <5 x 106 109/l
Platelets • RBCs (rare) • N.B.: Assess platelet count
1 hour and 24 hours after
platelet transfusion to
monitor platelet increment
Granulocytes Use and therapeutic effect are questionable due to the availability of recent appropriate antibiotic therapy for infected
neutropenic patients

Part I: 1.
 Table 2: Non-cellular Blood Components
Dose and
Component Volume Contents Indication Contraindications
Administration
FFP 200-250 • All coagulation • Replacement of • Volume expansion • Dose: 10-15 ml/kg
ml/pack factors (roughly coagulation • Nutritional causes • Administration of 15
1 unit of each factors as in: ml/kg body weight raises
/1 ml) - Liver disease the activity of the
• Albumin - Warfarin coagulation factors by 20-
• Igs overdose 30%
- Massive • Before use, should be
transfusion thawed in water bath
- DIC between 30-37°C
- TTP • Once thawed, should be
- When PT or used or otherwise kept in
PTT is at least refrigerator at 2-6°C and
1.5 times should be used within 6
-6-

normal (about hours of thawing

18 seconds) • Infuse using a standard
blood giving set over not
more than 2 hours
• Crossmatching is not
essential, give ABO
compatible plasma
 Table 2: Non-cellular Blood Components (Continued)
Dose and
Component Volume Contents Indication Contraindications
Administration
Liquid 200-250 • Stable Deficiency of stable Same as FFP Same as FFP
Plasma / ml/pack coagulation coagulation factors
factors
Frozen
• No labile
Plasma coagulation
factors (V and
VIII)
• Albumin
• Igs
Cryo- 20-30 • F VIII: • As alternative to Same as FFP • Dose: 1 pack / 10 kg
precipitate ml/pack > 70 U/pack F VIII concentrate • After thawing, transfuse
• Fibrinogen: in: Hemophilia A immediately over 15-20
>140mg/ pack • von Willebrand minutes
-7-

• F XIII: ≈50-75 disease • Infuse using a standard

IU/pack • As a source of blood giving set
• vWF: ≈ 100- fibrinogen in DIC • Must be infused within 6
150 IU/pack and liver failure hours of thawing
• F XIII • Crossmatching is not
• Fibronectin essential, give ABO
compatible units
CDP 150-250 Plasma from • TTP (for Same as FFP Same as FFP
ml/pack which ≈ half of exchange
content of transfusion)
fibrinogen and F • Deficiency of
VIII has been stable coagulation
removed as factors
cryoprecipitate • Hemophilia B

Part I: 1.
I.1.3. Special Processing of Blood Components

Blood components used for special clinical conditions, and for some
critically ill patients, need to be processed by specific techniques to reduce
the risk of certain adverse transfusion reactions and to improve the outcome
of the transfusion. Most of these processed components are currently
available. Special processing includes: leucocyte depletion/reduction,
washing, addition of diluent solutions, pooling, irradiation, freezing, and
aliquoting.

A. Leucocyte Depletion of PRCs or Platelet Concentrate:

Clinical impacts of leucocyte depletion are:
• Prevention of Febrile Non-Hemolytic Reaction (FNHR).
• Minimizing alloimmunization to HLAs and thus preventing platelet
refractoriness.
• Reduction of potential transmission of some viral diseases such as
CMV, HTLV I and II, and EBV.

N.B.: Other possible beneficial effects of leucocyte depletion include a

reduced risk of postoperative infection.
Methods:
1. Centrifugation: removal of buffy coat removes 78-80% of leucocytes.
2. Filtration: the most efficient method. Filtration can be carried out by
pre-storage or bedside filters. Filtration removes about 99.9% of
leucocytes.

-8-
B. Washing:

Part I: 1.
RBCs are washed to remove plasma proteins (to reduce anaphylactic
reactions) and in IgA negative patients. Automated cell washers are very
expensive. Manual washing is an open system, so RBCs should be used
within 24 hours to prevent bacterial growth. The Hct of washed PRCs is 65-
75%.

N.B.: Washing is not an ideal method for leucocyte depletion as it

removes only 70-80% of leucocytes.

C. Addition of a Diluent Nutritive Solution to PRCs:

Nutritive solutions such as SAGM are used to reduce viscosity and
facilitate transfusion of PRCs and to prolong their shelf life. The Hct of
PRCs in additive solution is 50-70%. SAGM is a nutritive solution
composed of saline, adenine, glucose and Mannitol. It can extend the life
span of RBCs up to 42 days.

D. Pooling:
RDP units separated from 4-6 donations can be pooled to produce a
therapeutic dose for adult patients. Pooling can also be done for
cryoprecipitate units.

-9-
E. Irradiation of Cellular Blood Products:
Mechanism of action:
It is performed by using a dose of 25 Gy (2,500 rad) of γ radiation. It is
the only acceptable methodology to prevent transfusion associated Graft
versus Host Disease (GvHD) that occurs when viable donor T lymphocytes
proliferate and engraft in susceptible individuals after transfusion.
Irradiation inactivates the proliferative capacity of T lymphocytes present in
cellular components.
Indications:
• Bone marrow transplant recipient (allogenic or autologous).
• Congenital Immune Deficiency Syndrome.
• Intrauterine transfusion.
• Low birth-weight neonates.
• Acute leukemia, lymphomas and patients receiving intensive
chemotherapy for solid tumors.
• AIDS.
• Directed blood donation from first and second-degree relatives.
• Blood components given to recipients, whether immunocompromised
or immunocompetent, which contain lymphocytes that are
homozygous for an HLA haplotype that is shared with the recipient.
This happens mostly when blood is donated from a FIRST DEGREE
RELATIVE.
• Bone marrow failure syndromes.
Precautions:
Irradiated red cells undergo an enhanced efflux of Potassium during
storage; irradiation should be done a few hours prior to transfusion.

- 10 -
F. Freezing of Cellular Blood Products:

Part I: 1.
Liquid nitrogen is used to store RBCs for 10-20 years using a
cryoprotectant. It is useful in very rare blood groups. (Not currently
available).

G. Aliquoting:
This process divides blood components into small aliquots to be used for
pediatrics and neonates. As the actual amount of blood transfused per
transfusion episode is small, a blood pack can be divided into multiple
satellite packs of approximately 50-100 ml each, allowing repeated
transfusions to be given to the same patient from a single donation unit and
one single individual in a closed system in order to reduce the risk of
bacterial contamination and alloimmunization.

- 11 -
Table 3: Time Needed for Special Processing of Blood Components
Storage
Shelf Life
Approximate Time Temperature
Component after
for Processing after
Processing
Processing

RBC: saline-washed 30 minutes 24 hours 4°C

RBC: thawed-
60 minutes 24 hours 4°C
deglycerolized

FFP: thawed 30 minutes 24 hours 4°C

Platelets: pooled 15 minutes 4 hours 22°C

Cryoprecipitate:
10 minutes 6 hours 4°C
thawed
Cryoprecipitate:
15 minutes 4 hours 4°C
pooled

- 12 -
I.2. Plasma Derivatives
Plasma derivatives are prepared by a pharmaceutical manufacturing

Part I: 2.
process from large volumes of plasma comprising many individual blood
donations. These derivatives include human albumin, coagulation factors,
and Igs.

I.2.1. Human Albumin Solutions

I.2.1.1. Preparations:

A. Albumin 5%: 400 ml Bottle:

• Contains 50 mg/ml of albumin.
• Contains 150 mg/l Sodium (hypertonic solution).
• More crystalloid than colloid.
• Transfusion rate 10 ml/min.

B. Albumin 20-25%: 100 ml Bottle:

• Contains 200-250 mg/ml albumin.
• Poor salt and chloride (hyperoncotic solution).
• More colloid than crystalloid, preferred in hepatic patients.
• Transfusion rate 0.2-0.4 ml/min.

N.B.: See literature with each pack for specific details.

I.2.1.2. Indications:
• Replacement fluid in plasma exchange (use albumin 5%).
• Treatment of diuretic resistant edema in hypoproteinemic patients as
nephrotic syndrome or ascites (use albumin 20% with a diuretic).
• Hypovolemia following burns (use albumin 5%).

- 13 -
I.2.1.3. Precautions:
Albumin 20% may cause acute expansion of intravascular volume with
risk of pulmonary edema.

I.2.1.4. Contraindications:
Not used for nutrition, as albumin is an expensive and inefficient source
of essential amino acids.

I.2.2. Coagulation Factor Concentrates

A. F VIII Concentrates:
Preparation:
Lyophilized concentrate containing different amounts of F VIII. Number
of units is stated on each vial.
Indications:
• Moderate to severe F VIII deficiency (hemophilia A).
• Some cases of von Willebrand disease: in some patients resistant to
DDAVP, intermediate purity F VIII concentrates are used as they
contain vWF.
Dose:
Dose is calculated according to body weight, desired level of F VIII
activity and clinical situation.
Alternatives:
• Cryoprecipitate, FFP.
• Recombinant F VIII concentrate.

- 14 -
B. Multifactor Concentrate:
Preparation:

Part I: 2.
Lyophilised concentrate containing large amounts of F IX. It also
contains F II, VII, and X. Number of units is stated on each vial.
Indications:
• F IX deficiency (hemophilia B).
• Congenital F VII or X deficiency.
• Hemophilia with F VIII inhibitors.
Dose:
As Factor VIII concentrate.
N.B.: Pure F IX concentrate is also available.

I.2.3. Immunoglobulins (Igs)

These are concentrated aqueous solutions of gamma globulins
containing a high concentration of antibodies.

A. Anti RhD Ig:

Indications:
• For prevention of Hemolytic Disease of Newborn (HDN) in RhD
negative mothers.
• For treatment of ITP in Rh positive non-splenectomized patient.
Dose:
If the fetus is RhD positive, 300 µg are administered IM within 72 hours
of delivery (it can be administered within 2 weeks after birth but with
questionable effect).

- 15 -
B. Igs for IV Use:
Indications:
• ITP.
• Treatment of immune deficiency states.
• Hypogammaglobulinemia.
• HIV related disease.
• SLE.

C. Igs for IM Use:

Indications:
• Prevention of specific infections (passive immunization), e.g.:
Hepatitis B Igs, rabies and tetanus. However, active immunization
(vaccination) is preferred whenever possible.
• Treatment of immune deficiency states.

- 16 -
I.3. Blood Transfusion Alternatives
BLOOD TRANSFUSION SHOULD BE ORDERED ONLY IF THERE IS NO

Part I: 3.
OTHER ALTERNATIVE TO PREVENT MORBIDITY OR MORTALITY.
ACCORDINGLY, ALTERNATIVES SHOULD ALWAYS BE CONSIDERED IN
EACH CASE AND THE BENEFITS OF BLOOD TRANSFUSION SHOULD
OUTWEIGH THE POSSIBLE RISKS.

Blood alternatives include:

• Replacement fluids.
• Pharmaceuticals.
• Autologous blood transfusion.

I.3.1. Replacement Fluids

Replacement fluids are used to replace abnormal losses of blood, plasma
or other extracellular fluids. Fluid therapy should be adjusted to
hemodynamic response, and central venous and pulmonary wedge
pressures.

These fluids include:

A. Crystalloids (Table 4):
A crystalloid solution is an aqueous solution of small molecules which
easily pass through capillary membranes. Crystalloid replacement fluids
contain a similar concentration of Sodium to plasma. This ensures that they
are excluded from the intracellular compartment since the cell membrane is
generally impermeable to Sodium. However, they readily cross the capillary
membrane from the vascular compartment to the interstitial compartment to
be distributed throughout the entire extracellular compartment.
B. Colloids (Table 5):
A colloid solution contains large molecules and has a higher molecular
weight than crystalloid solution. Its passage through capillary membranes is

- 17 -
restricted and initially tends to remain within the vascular compartment.
Colloids maintain plasma colloid oncotic pressure and the most part remain
intravascular, whereas crystalloids rapidly equilibrate with and distribute
throughout the entire extracellular fluid space. Colloids are more effective
in restoring normal intravascular volume and cardiac output. Most colloids
have intravascular half-lives from 3-6 hours, while crystalloids have half-
lives of 20-45 minutes.

The Ideal IV Replacement Fluid:

The ideal IV replacement fluid should occupy volume in the vascular
compartment. It should also be:
• Easily available and inexpensive.
• Non-toxic.
• Non-allergic or infectious.
• Totally metabolized or eliminated from the body.

I.3.2. Pharmaceuticals
There are some pharmaceuticals that have been mentioned in the
literature to reduce the need for blood transfusion. These include:
recombinant growth factors, Desmopressin Acetate (DDAVP), anti-
fibrinolytic agents, Vitamin K, recombinant products for hemostasis, and
red cell substitutes.

- 18 -
Table 4: Crystalloids
Normal Saline Ringer’s Lactate
Composition Isotonic solution of NaCl Similar to intracellular fluid
in a near physiological so can be used in large
concentration/l: 154 mEq volumes without disturbing
of Na and 154 mEq of Cl the electrolyte balance; it
contains/l: 130 mEq Na, 109
mEq Cl, 4 mEq K, 3 mEq
Ca, and 28 mEq lactate
Storage In a cool place
Dosage At least 3 times the blood volume lost (1/3 of the crystalloid
remains in the vascular compartment)
Plasma Half-Life Short, approximately 45 minutes, rapidly distributed throughout
intracellular compartment
Indication Replacement of blood volume and other extracellular fluid
losses
Precautions • Caution in situations where local edema may aggravate
pathology, e.g. head injury, ascites, etc.
• May precipitate fluid overload and heart failure
Contraindications Do not use in patients with established renal failure
Side Effects Tissue edema can develop when large volumes are used

N.B.: Dextrose 5% should not be used as a replacement fluid.

- 19 -
 Table 5: Colloids
Gelatins
(Hemocel, Gelofusine)
Molecular chains of gelatins
prepared from bovine
collagen with an average
molecular weight of 30,000,
Composition such as:
• Hemocel: 3.5% gelatin in
0.9% NaCl
• Gelofusine: 4% gelatin in
0.9% NaCl
At room temperature below
Storage
25°C, stable for 5 years
- 20 -
Dosage No known dosage limit
Plasma Half-Life Approximately 4 hours
Elimination Renal excretion
Dextran 60 and Hydroxyethyl Starch
Dextran 70 (Metastarch, Hesteril or HES)
Macromolecular glucose
chains with an average
molecular weight of 70,000
Macromolecular manufactured from
• 3% Dextran 60 in NaCl
natural starch with a range of
0.9%
molecular weight of 450,000
• 6% Dextran 70 in NaCl
• 6% metastarch in NaCl 0.9%
0.9%
• 6% Dextran 70 in 5%
dextrose
At room temperature below
In a cool place
25°C
• Dextran 60: should not
exceed 50 ml/kg in 24
hours Should not exceed 20 ml/kg in 24
• Dextran 70: should not hours
exceed 25 m1/kg in 24
hours
Approximately 12 hours 12-24 hours
Predominantly renal
Predominantly renal excretion
excretion
20
 Table 5: Colloids (Continued)
Gelatins
(Hemocel, Gelofusine)
Replacement of blood
Indications
volume
Not used in patients with
Contraindications established renal failure
• May precipitate heart
failure
- 21 -
• Caution in renal
Precautions insufficiency
• Do not mix hemocel with
citrated blood because of its
high calcium concentration
• Minor allergic reactions
due to histamine release
• Transient increase in BT
may occur
Side Effects
• Hypersensitivity reactions
may occur, including rare
severe anaphylactic
reactions
Dextran 60 and Hydroxyethyl Starch
Dextran 70 (Metastarch, Hesteril or HES)
• Replacement of blood
volume
Replacement of blood volume in
• Prophylaxis of post-
severe hypovolemic shock
operative venous
thrombosis
• Not used in patients with pre-
existing disorders of hemostasis and
Not used in patients with
coagulation
pre-existing disorders of
• Not used in patients with established
hemostasis and coagulation
renal failure
• Allergic reaction to its components
• Coagulation defects may
occur
• Platelet aggregation • Coagulation defects may occur
inhibited • May precipitate fluid overload and
• May interfere with heart failure
compatibility testing of
blood
• Same as gelatins
• Serum amylase level may
• Minor allergic reactions due to
rise (not significant)
histamine release
• HES is retained in cell of
• Transient increase in BT may occur
reticulo-endothelial system,
(the long-term effects of • Hypersensitivity reactions may
occur, including rare severe
this are unknown)
anaphylactic reactions
• Anaphylactic reactions may
develop during transfusion
21
Part I: 3.
 Table 6: Characteristics of the Most Widely Used Pharmaceuticals
Drug Indications Administration Side Effects
a) Recombinant Growth Factors: They stimulate endogenous blood cell production
Treatment of anemia in:
• Renal failure
• Chronic disease
• EPO • Bone marrow suppression
• Myelodysplastic syndrome especially RA, RARS
• CLL, multiple myeloma
• Treatment of chemotherapy induced neutropenia
• Autologous marrow transplantation
• GM CSF
• Allogenic marrow transplantation
• Bone marrow suppression
b) DDAVP: It is a synthetic analogue of vasopressin without significant pressor activity
• Platelet function disorders in cirrhosis, uremia. • IV or SC to treat • Tachyphylaxis
• Drug-induced, primary myelodysplastic syndromes. bleeding, or • Water retention
- 22 -

• Mild to moderate hemophilia A with inhibitors prophylactically and hyponatremia

• von Willebrand disease. before a surgical • Loss of biologic
procedure effect after
• Not repeated before repeated
24-48 hours administration
• Effect on vWF occurs • Facial flushing
within 30 min. and and mild
lasts for 4-6 hours hypotension
• Contraindicated
in rare types of
vW syndrome

22
Table 6: Characteristics of the Most Widely Used Pharmaceuticals (Continued)
c) Anti-Fibrinolytic Agents: They inhibit fibrinolysis
• EACA (Amicar)
• Tranexamic Acid (Cyclokapron)
• Aprotinin (Trasylol)
• Generalized fibrinolysis as in prostatic surgery and • Local or systemic Serious thrombotic
hepatic transplantation • If renal function is complications in
• Control of hemorrhage following dental extraction impaired, reduce the excessive doses
in hemophilia dose
• Control of upper GIT bleeding • Only to be used by
• Control of bleeding due to severe thrombocytopenia. experienced
• Dysfunctional uterine bleeding according to physicians
Randomized Controlled Trials (RCT)
• Aprotinin is used during cardiac surgery
d) Vitamin K:
• Depletion of Vitamin K body stores as in • IV or SC if liver
nutritionally depleted hospitalized patients function is adequate
• Vitamin K deficiency due to antibiotic use
• Obstructive jaundice, fat malabsorption syndrome
• Warfarin-type anticoagulants inhibit action of
Vitamin K
• Prophylaxis against hemorrhagic disease of the
newborn
e) Recombinant Products for Hemostasis:
• Recombinant F VIII
• Recombinant F VIla (Novoseven)
f) Red Cell Substitutes and Artificial Oxygen Carriers: Trials are still being conducted (not yet available)
• Stroma free Hb
• Recombinant Hb as per-fluorocarbon products

23
Part I: 3.
I.3.3. Autologous Blood Transfusion
Autologous blood transfusion is the collection, processing and re-
infusion of the patient’s own blood. This is done to avoid the risk of some
immunological and infection transmission problems associated with
homologous blood.

Types:

A. Preoperative Blood Donation (Deposit):

This type of autologous donation is used if the surgical procedure is
likely to result in sufficient blood loss so as to require transfusion. It
involves the collection, processing and storage of the patient’s own blood
before surgery. The patient should be fit to donate blood and should be
given iron supplements one week before and a few months after donating
blood. According to an organized plan, 3 to 5 units can be collected from
suitable candidates.

B. Acute Normovolemic Hemodilution:

This is performed by removing a predetermined volume of the patient’s
own blood immediately prior to surgery (after induction of anesthesia) and
simultaneously replacing it with sufficient crystalloid solution (3 ml for
every 1 ml of blood collected) or colloid solution (1 ml for every 1 ml of
blood collected) to maintain the blood volume. The autologous blood
collected can be subsequently re-infused during or after surgery. This
procedure has the advantage of containing coagulation factors and platelets.
It is used in cardiovascular surgery, particularly open-heart surgery, because
the fresh unit of autologous blood will contain coagulation factors and
platelets. It has also the advantage of saving red cells from being lost during
an operation.

- 24 -
C. Blood Salvage:
Blood salvage is the collection of blood shed from a wound or body
cavity and its subsequent re-infusion into the same patient. Blood is
salvaged, filtered, suspended in saline solution and re-infused using a cell
saver. Cell savers can be used intra-operatively or post-operatively in major
procedures with acute blood loss of more than 1,000 ml such as cardiac or
orthopedic surgery.

- 25 -
I.4. Hospital and Bedside Transfusion Practice
Hospital transfusion practice should be supported by SOPs based on
guidelines as described in this handbook. These will cover the following:
• Blood ordering policy for elective and emergency situations.
• Bedside transfusion practice including storage, transportation,
handling, dispensing, administration of blood and blood components
and monitoring of the transfused patient.
• Investigating and reporting adverse transfusion reactions and their
management.
• Documentation for all steps of transfusion to permit traceability of
every blood unit from donor to recipient.
Clerical errors in bedside transfusion practice have been shown to be the
major cause of morbidity and mortality associated with transfusion.
Therefore a quality control system should be implemented to allow
continuous monitoring of the whole transfusion process.
The safety of the patient requiring transfusion depends on cooperation
and effective communication between clinical and blood bank staff.

I.4.1. Ordering Blood

The decision for blood transfusion should:
• Follow national guidelines for ACUB described in this handbook.
• Be taken by the most senior, experienced staff member.
• Take into consideration the clinical assessment and the laboratory
results of the individual patient.
• Be taken after weighing risks versus benefits.
• Be taken after considering other alternatives and lines of treatment.

Annex 1 shows a checklist which can be used by clinicians before

prescribing blood.

- 26 -
1.4.2. Blood Ordering Policies
A. Ordering Blood for Elective Surgery and Cold Cases:

Part I: 4.
• Each hospital should ensure that a blood request form is used. It
should be completed accurately and legibly and signed by the
clinician. (See Annex 2 for a sample blood request form) The blood
request form should include the patient’s details as well as the
reasons for transfusion so that the blood bank can select the most
suitable product.
• In medical and other non-surgical cases, national guidelines on the
ACUB should always be followed.
• The timing of requests for blood for elective surgery should comply
with rules set up in the hospital (usually not less than 24 hours).
• The blood-ordering schedule should reflect the clinical team’s usual
practice. Annex 3 shows an example of a Maximum Surgical Blood
Ordering Schedule (MSBOS). The goal of a MSBOS is to limit the
number of units crossmatched compared to the usual number
transfused. This schedule can be developed for each hospital by
analyzing blood usage in the facility for each specific elective
surgical procedure.
• For surgical procedures with an average usage of less than 0.5 unit of
blood per operation, a type and screen procedure is recommended.
With a type and screen, the transfusion service determines the
patient’s ABO group and Rh type, and performs an antibody screen.
In the case of a negative antibody screen, the patient can receive
ABO and Rh type specific blood after rapid X-matching. In the case
of detection of clinically significant antibodies, blood lacking the
specific antigen(s) is crossmatched.
• Development and acceptance of the MSBOS and type and screen
programs for elective surgery requires close cooperation between the
transfusion service, surgeons and anesthesia personnel.

- 27 -
Blood samples for compatibility testing:
It is mandatory that the patient’s blood sample be drawn into a sample
tube that is correctly labeled and uniquely identifiable with the patient.
Information on the label should include: the patient’s full name, the
patient’s ward, the patient’s hospital reference number, date, and signature
of person taking the sample. Two samples are needed; 10 ml in a plain tube
for crossmatching and 3 ml in an EDTA tube for blood grouping. Smaller
samples are accepted from infants and neonates.

N.B: Any failure to follow the above procedures can lead to an

incompatible transfusion.

Compatibility testing between donor’s red cell and patient’s serum:

All pre-transfusion testing procedures should provide the following
information about both the units of blood and the patient regarding:
• ABO group and RhD typing.
• Presence of red cell antibodies that could cause hemolysis in the
recipient (if present).
This test normally takes about 1 hour to be completed. In the case of the
presence of antibodies, time for crossmatching may be prolonged.
Shortened procedures are possible but may fail to detect some
incompatibilities.
In the case of non-availability of the same blood group as the patient,
non-group specific blood can be used according to the pattern shown in
Table 7.

- 28 -
 In the case of Rh negative recipients they should ideally have Rh
negative red cells, especially females during the childbearing period. In
other conditions or in life-threatening situations Rh positive units may be

Part I: 4.
given with some precautions including:
• Documentation to be available for use in future transfusion or
pregnancy.
• Anti-D Ig injection to be considered within 72 hours of transfusion.

Table 7: ABO Compatible Blood Components

Compatible
Recipient Compatible
Compatible Compatible Platelets
ABO Platelets
Plasma Red Cells (First
Group (Second Choice)
Choice)
A A, AB A, O A, AB B, O
B B, AB B, O B, AB A, O
O O, A, B, AB O O A, B, AB
AB AB AB, O, A, B AB A, B, O

- 29 -
B. Ordering Blood in the Case of an Emergency:
1. In an emergency, insert an IV cannula, use it to draw the blood
sample for compatibility testing, set up an IV infusion and send the
blood sample to the blood bank as quickly as possible.
2. For each patient, the blood sample tube and the blood request form
must be clearly labeled with the patient’s name and unique hospital
reference number. If the patient is unidentified, some form of
emergency admission number should be used. Use the patient’s
name only if you are sure you have correct information.
3. If an additional blood request form has to be sent for
crossmatching for the same patient, use the same identifiers used
on the first request form and blood sample so the blood bank staff
know they are dealing with the same patient.
4. If there are several staff members working with emergency cases,
one person should take charge of ordering blood and
communicating with the blood bank about the incident. This is
especially important if several injured patients are involved at the
same time.
5. Inform the blood bank of how urgent the blood is needed for each
patient using the relevant request form.
6. Make sure that both you and the blood bank staff know:
• Who is going to bring the blood to the patient or collect it
from the blood bank.
• Where the patient will be. For example, if your patient is just
about to be transferred to another part of the hospital for an X-
ray, make sure the blood will be delivered to the X-ray room.
N.B.: If blood is needed immediately use Group O (and possibly Rh
negative) red cells, especially if there is any risk of errors in patient
identification. During an acute emergency, this may be the safest way to
avoid a serious mismatched transfusion.

- 30 -
I.4.3. Storage and Transportation of Blood Components
Maintaining optimal conditions during the storage and transportation of

Part I: 4.
blood components (COLD CHAIN) will ensure the following:
• Delaying or preventing physical, chemical or mechanical changes
detrimental to blood constituents.
• Minimizing microbial contamination and proliferation.

- 31 -
Storage lesions:
These are the biochemical changes that occur during blood storage
between 2-6oC.
Table 8: Characteristics of WB Stored for 35 Days in CPDA-1
Storage Time (Days)
0 7 14 21 35
Plasma Dextrose (mg/dl) 432 374 357 324 282

Plasma Sodium (mEq/l) 169 162 159 157 153

Plasma Potassium (mEq/l) 3.3 12.3 17.6 21.7 17.2

Plasma Chloride (mEq/l) 84 81 79 77 79

Plasma Bicarbonate (mEq/l) 12.0 17.0 12.5 12.2 8

WB pH 7.16 6.94 6.93 6.87 6.73

WB Lactate (mg/dl) 19 62 91 130 202

Plasma LDH (Units) 296 1,002 1,222 1,457 1,816

WB Ammonia (mg/dl) 82 280 423 521 703

Plasma Hemoglobin (mg/dl) 0.5 13.1 24.7 24.7 45.6

WBC (103/ml) 7.2 4.0 3.0 2.8 2.4

Hct (%) 35 36 35 36 36

RBC Hb (g/dl) 12 12 12 12 12
6
RBC (10 /ml) 4.0 4.0 3.9 3.9 3.9

RBC 2,3-DPG (mmol/g Hb) 13.2 0 0 0 0.7

RBC ATP (mmol/g Hb) 4.18 0 0 0 2.40

- 32 -
Storage and transportation of red cell components:
• Stored at temperature +4[±2]oC in specially designed refrigerators.

Part I: 4.
• Shelf life will depend on preservative and anti-coagulant used in the
pack.
• Should never be allowed to freeze as freezing causes hemolysis of
RBCs.
• Blood bags are kept in the refrigerator in an upright position either
standing or hanging for easy inspection of signs of deterioration.
• During transportation, keep temperature range between +2-6oC by
using cool boxes with ice packs and insulators (never let blood touch
ice packs).

Storage and transportation of frozen components (FFP and cryoprecipitate):

• Stored in deep freezers -30oC or below for 1 year or in -18oC for 6
months only.
• Should be always kept frozen solid.
• Stored in lying position to prevent cracking.
• Transported in cool boxes with ice packs or dry ice to maintain pack
frozen solid.

Storage and transportation of platelet concentrate:

• Stored between +22[±2]oC with continuous gentle agitation (best in
special platelet shaker incubator).
• Shelf life is 3-5 days, depending on the type of pack used.

- 33 -
I.4.4. Handling of Blood Components
• Maintain sterile aseptic conditions during all steps of handling of
blood and blood components.
• At the time of release from the blood bank, identify the intended
recipient and the requested component using written documentation.
• If the ward or operating room does not have a refrigerator specially
designed for blood storage, blood should be kept in the blood bank
and issued immediately prior to transfusion. Ideally, one unit is
released at a time unless the transfusion need is especially urgent.
• Every blood pack should be inspected for signs of deterioration (e.g.
clots, hemolysis, leakage, discoloration, etc.):
o Before it is issued from the blood bank.
o On arrival in the ward or operating theatre.
o Before transfusion (if it is not used immediately).
If any discrepancies are found on identification, or the pack appears
abnormal in any way, the unit must not be transfused and the blood bank
must be informed immediately.

Discoloration or signs of any leakage may be the only warning

that the blood contains bacterial contamination and could cause
a severe or fatal reaction when transfused.

- 34 -
A. Inspection of PRCs and WB:
The unit should not be transfused if

Part I: 4.
the unit has been (or may have been) out of the refrigerator for longer than
30 minutes
Or
The plasma looks pink or red
Or
The red cell compartment looks purple or black

- 35 -
B. Inspection of FFP and Cryoprecipitate:
• Check for cracks or turbidity.
• Unusual turbidity of the thawed component may indicate
contamination and thus should be discarded.

C. Inspection of Platelet Concentrate:

Check for turbidity, green discoloration, or leakage and discard if
present.

- 36 -
Warming of blood:
• Routine warming of blood is not recommended.

Part I: 4.
• It is not needed for patients receiving 1-3 units of blood over several
hours.
• Keeping the patient warm is probably more important than warming
the infused blood.
• Transfusion at rapid rates (>100 ml/min) for 30 minutes of
refrigerated blood can lower the temperature of the sino-atrial node
to below 30oC and cause ventricular arrhythmias and cardiac arrest.
• Special warmers should be used in these cases. They have visible and
audible alarm systems and do not allow overheating of the blood.

Other cases requiring warmed blood are:

• Exchange transfusion in infants.
• Patients with clinically significant cold agglutinins.
• Large volume-rapid transfusions: (adults > 50 ml/kg/hr, children > 15
ml/kg/hr).

Automated warmers are the only proper method for

warming blood (if necessary). Other methods such as tap
water, hot blankets or uncontrolled temperature devices are
strictly forbidden.

- 37 -
Thawing of frozen blood components (FFP & cryoprecipitate):
This is done in a water bath (between 30-37oC). Higher temperatures
can destroy proteins and coagulation factors. During the thawing, the bags
should be kept in an upright position and wrapped in another plastic bag to
prevent water contact with the entry port in order to avoid contamination.
Thawed components should be infused within 30 minutes of thawing. If this
is not possible, they can be kept in a refrigerator at 2-6oC and transfused
within 24 hours (transfusion within 6 hours of thawing is preferable as
labile coagulation factors degrade rapidly).
Transfusion should be completed within 1-2 hours for FFP and 15-20
minutes for cryoprecipitate.

Never refreeze FFP or cryoprecipitate after thawing.

- 38 -
I.4.5. Administration of Blood and Blood Components

A. Before Transfusion:

Part I: 4.
1. Verify physician’s order (Blood Request Form).
2. Check patient and blood unit identity: the patient’s full name, the
patient’s ABO and RhD group, unique donation number of blood
pack, and the blood group of the blood pack.
Annex 4 shows an example of a compatibility label which should
be affixed to the blood pack throughout the transfusion procedure.
3. Document that checking is complete and correct, who performed
the checking and who started the transfusion.
4. Record the date and time of the infusion, the name and volume of
component(s) and the identification number.
5. Record the patient’s pre-transfusion vital signs: temperature, blood
pressure, pulse, and respiratory rate.
6. The patient should be informed about the transfused component(s)
and should be instructed to report immediately any unusual
symptoms during the transfusion: headache, loin pain, urticaria,
shivering, flushing, or shortness of breath. Signs of incompatibility
under general anesthesia such as tachycardia, hypotension and
hematuria should be in the physician’s mind.
7. Use a separate IV line if an IV fluid other than normal saline has to
be given at the same time as the blood components.
8. Check instructions on the blood giving sets or filters (PRCs or
platelet filters).
9. Check the expiry date of components and any signs of
deterioration (see I.4.3. & I.4.4.).

No medication should be added to the transfused blood or in

the infusion line.

- 39 -
B. During Transfusion:
Blood and blood components should be transfused through a standard
infusion set having in-line filters with a pore size of 170-280 µ, a drip
chamber and tubings. These filters are used to retain blood clots and
particles potentially harmful to the recipient.
1. Start the infusion slowly (2 ml/min.).
2. During the first 15 minutes of the transfusion, the patient should be
observed and vital signs should be recorded.
3. If the condition of the patient is satisfactory, increase the rate of
infusion and observe the patient periodically throughout the
transfusion (every 30 min.).
4. A trained person (resident physician and nurse) should monitor the
transfused patient and respond immediately if any adverse effects
occur.
Annex 5 shows a sample monitoring sheet for a transfused patient.

- 40 -
Table 9: Time Limits for Infusion of Specific Components

Part I: 4.
Component Start Infusion Complete Infusion
Within 30 minutes of Within 4 hours (or less in
Red Cell Components removing pack from high ambient
refrigerator temperature)
Platelet Concentrates Immediately Within 20 minutes

FFP Within 30 minutes Within 1-2 hours

Cryoprecipitate Within 30 minutes Within 20 minutes

Carefully adjust the rate and volume of the transfusion in elderly

patients, and patients with congestive heart failure because of the
risk of volume overload.

Consider the use of diuretics in these cases.

If the blood pack cannot be infused within 4 hours, divide and
store in the blood bank until used, as in the case of infants and
elderly patients.

In high ambient temperature these time limits should be
shortened.

- 41 -
C. After Transfusion:
1. Record the time of ending the transfusion and the person who
performed the task (resident physician or nurse).
2. Check the patient’s vital signs.
3. Monitor the patient for any delayed transfusion reactions.
4. Monitor the patient for expected outcome.
5. Calcium gluconate may be used after massive transfusion of stored
WB, resulting in citrate toxicity, Calcium chelation and
hypocalcemia.

I.5. Adverse Transfusion Reactions

Transfusion reactions can be classified in a simple way in order to
recognize them easily, understand their underlying causes, and know how to
prevent, manage and report them.

I.5.1. Immediate Complications

Immediate transfusion reactions occur during or shortly after (within 24
hours) the transfusion. They can be broadly classified in the following three
categories according to their severity and the appropriate clinical response:
• Category 1 – Mild Reactions:
o Mild hypersensitivity in the form of allergic urticarial
reactions.
• Category 2 – Moderately Severe Reactions:
o Moderate-severe hypersensitivity (severe urticarial reactions).
o FNHRs:
1. Antibodies to WBCs, platelets.
2. Antibodies to proteins, including IgA.
o Possible bacterial contamination (early signs).
o Pyrogens.

- 42 -
 • Category 3 – Life-Threatening Reactions:
o Acute intravascular hemolysis, e.g. ABO incompatibility.
o Bacterial contamination and septic shock.

Part I: 5.
o Fluid overload.
o Anaphylactic reactions.
o TRALI.

I.5.2. Delayed Complications

Delayed complications from transfusion basically fall into two categories:

A. Delayed Complications from Transfusion:

Occurring days, months or even years after the transfusion has been
completed, they include:
• Delayed hemolytic reaction.
• Post-transfusion purpura.
• TA-GvHD.
• Iron overload (in patients who receive repeated transfusions).

B. Transfusion-Transmitted Infections (TTIs):

• Viral hepatitis B and C.
• HIV-l and HIV-2.
• HTLV-l and II.
• Treponema pallidum (Syphilis).
• Chagas disease
• Malaria.
• CMV.
• Other rare infections: e.g. human Parvovirus B19 and hepatitis A,
HHV-8, vCJD.
• WNV.

- 43 -
 When an acute reaction first occurs, it may be difficult to decide on its
cause and severity as the signs and symptoms may not initially be specific
or diagnostic. However, with the exception of allergic urticaria and FNHRs,
all are potentially fatal and require urgent treatment.
In an unconscious or anaesthetized patient, hypotension and
uncontrolled bleeding may be the only signs of an incompatible transfusion.
In a conscious patient undergoing a severe hemolytic transfusion
reaction, signs and symptoms may appear within minutes of infusing only
5-10 ml of blood. Close observation at the start of the infusion of each unit
is essential.
If an acute transfusion reaction occurs, first check the blood pack labels
and the patient’s identity. If there is any discrepancy, stop the transfusion
immediately and consult the blood bank.

General Guidelines for Management of Acute Adverse Transfusion

Reactions:

1- Stop transfusion immediately.

2- Notify the physician responsible.
3- Keep the IV line open by infusion of 0.9% normal saline.
4- Check patient’s identity, unit details and compatibility label.
5- Measure vital signs.
6- Diagnose and treat accordingly.

Guidelines for the recognition and management of acute transfusion

reactions are shown in Table 10.
Drugs and dosages that might be needed in managing acute transfusion
reactions are shown in Table 11.

- 44 -
 Table 10 Guidelines for Recognition and Management of Acute Transfusion Reactions
Reaction Cause Signs and Symptoms Management
Onset is either rapid or up to
• Stop transfusion
1 hour from the start of
• Give antihistaminics
Patient has Abs against transfusion
plasma proteins in • Restart transfusion at slower rate with
transfused component closer monitoring
1- Allergic In mild cases: rash, urticaria
Reactions and itching • In severe cases:
(Mild, Moderate or Severe cases are due to - Treat shock by IV fluids and
Severe) infusion of IgA to IgA- In severe cases: chills, adrenaline
deficient patients having flushing, hypotension, shock, - Hydrocortisone may be needed
Abs dyspnea, tachycardia, - Prophylaxis: pre-transfusion
abdominal cramps, nausea, antihistaminics and transfusion of
vomiting, diarrhea washed blood components
• Stop transfusion
- 45 -

2- Febrile Non- • Give antipyretics such as Paracetamol

Hemolytic Patient’s Abs against Fever < 2°C, tachycardia, • Restart transfusion at slower rate with
Transfusion Ags on leucocytes in headache, flushing, chills, closer monitoring
Reactions transfused component muscle pain, hypotension • Prophylaxis: pre-transfusion antipyretics
(FNHTRs) and transfusion of leucocyte-depleted
blood components

45
Part I: 5.
 Table 10 Guidelines for Recognition and Management of Acute Transfusion Reactions (Continued)
Reaction Cause Signs and Symptoms Management
• Stop transfusion
• Check unit and patient’s identity
• Treat shock and maintain blood pressure
by saline infusion
• Maintain urine flow by diuretic IV,
Mannitol (urine volume > 75 ml/hour)
Onset is immediate:
• Monitor urine volume and other vital
fever, chills, burning pain in
signs closely
IV line site, chest pain, loin
ABO incompatibility • Obtain blood and urine samples for
pain, dyspnea, nausea and
3- Acute Hemolytic leading to hemolysis, analysis
vomiting, hypotension,
Reaction DIC and acute renal • Send blood pack, infusion set, and
hemoglobinuria and
failure samples to blood bank with a notification
hemoglobinemia, anuria,
form for re-checking and re-
- 46 -

bleeding in the form of

oozing from puncture sites crossmatching
• Prophylaxis:
- Proper checking of patient and unit
identity before transfusion
- Careful monitoring of transfused
patient for each unit especially
during first 20 minutes
Rapid infusion or great
Onset occurs after infusion of
volume infusion
significant volume: • Stop transfusion
4- Circulatory hypertension, rapid bounding • Give Oxygen
Mainly in extremes of
Overload pulse, high respiratory rate, • Give diuretic IV
age or with
severe dyspnea , cough, high • Provide cardiopulmonary support
cardiovascular function
CVP, nausea
impairment

46
 Table 10 Guidelines for Recognition and Management of Acute Transfusion Reactions (Continued)
Reaction Cause Signs and Symptoms Management
• Stop transfusion
• Replace IV set and maintain IV line open
by saline solution.
• Obtain blood samples for culture (aerobic
Bacterial contamination and anaerobic)
Onset is immediate:
of transfused component, • Start immediately broad spectrum
5- Bacterial Sepsis fever > 2°C, rigors, chills,
mainly occurs with antibiotics
shock, respiratory symptoms
platelet transfusion • Prophylaxis:
- Proper collection, storage and
handling of blood components
- Inspection of components before
transfusion
Abs in donor’s plasma
- 47 -

react against patient’s

leucocytes causing acute Onset is immediate or up to 4
6-Transfusion • Stop transfusion
severe microvascular hours after transfusion.
Related Acute • Treat as acute respiratory failure by
lung injury Severe dyspnea and cyanosis,
Lung Injury intubation, ventilation and provide 100%
hypotension, pulmonary
(TRALI) Oxygen support
Implicated donors are exudate, normal CVP.
mostly multiparous
women

47
Part I: 5.
Delayed Transfusion Reactions:

1- Delayed Transfusion Hemolysis

Onset is 2-7 days post-transfusion.
Patient was previously immunized to a blood group Ag usually by
transfusion or pregnancy.
It is manifested by worsening anemia and jaundice, usually
asymptomatic.
2- Post- transfusion Purpura
Onset is 5-14 days post-transfusion.
Patient produces Ab against a platelet specific antigen. This Ab will form
immune complexes with transfused platelet antigen leading to clearance
of most circulating platelets.
It is manifested by severe thrombocytopenia which lasts for up to 1-2
weeks.
It is a self-limited condition, but if there is bleeding IV Igs or plasma
exchange can be used. In severe life-threatening cases, transfusion of
platelets lacking the specific antigen can be of help.
3- Transfusion – Associated Graft versus Host Disease (TA-GvHD)
Onset is 4-30 days post-transfusion.
It is due to engraftment of viable immunocompetent donor T
lymphocytes into recipient.
It is manifested by rash, fever, diarrhea, liver dysfunction,
lymphadenopathy and pancytopenia. Prognosis is poor.
It occurs in immunosuppressed patients and also in immunocompetent
patients receiving blood components from first degree blood relatives.
It can be prevented by irradiation of blood components.
4- Iron Overload
It occurs in repeatedly transfused patients, e.g. thalassemic patients.
Iron is deposited in liver, heart and endocrine glands with consequent
clinical manifestations.
Effects can be minimized by the use of chelating agents and regular
monitoring of susceptible organ functions.

- 48 -
Table 11: Drugs that May Be Required to Manage Acute Transfusion
Reactions
Relevant Route and

Part I: 5.
Type of Drug Name Notes
Effects Dosage
IV Expands blood Normal saline If patient is Avoid colloid
volume hypotensive, solution
Replacement 20-30 ml/kg over
Fluid 5 min.
Reduces fever and Paracetamol Oral or rectal, 10 Avoid
inflammatory mg/kg aspirin-containing
Antipyretic response products if patient
has low platelet
count
Inhibits histamine- Chlorphenira- IM or IV, 0.1
Antihistamine mediated responses mine mg/kg
Inhibits immune- Adrenaline 0.01 mg/kg (as Dose may be
mediated 1:1000 solution) repeated every 10
bronchospasm by slow IM minutes according
injection) to BP and pulse
Bronchodilator until improvement
Consider: By nebuliser, occurs
Salbutamol
Aminophylline 5 mg/kg
Increases Dopamine IV infusion Dopamine in low
myocardial 1 µg/kg/min doses induces
contractility vasodilatation and
improves renal
perfusion
Inotrope
Dobutamine IV infusion 1-10 Doses above 5
µg/kg/min µg/kg/min cause
vaso-constriction
and worsen heart
failure
Inhibit fluid re- Frusemide Slow IV infusion
absorption from of 1 mg/kg
Diuretics ascending loop of
Henle
Maintain alkaline Mannitol 100 ml of 20%
Polysaccharide urine output > 75 Mannitol
ml/hour

- 49 -
Investigations of Adverse Transfusion Reactions:
Immediately report all acute transfusion reactions with the exception of
hypersensitivity (Category 1) to the doctor responsible for the patient and
to the blood bank that supplied the blood. If you suspect the patient is
having a severe life-threatening reaction, seek help immediately from the
duty anesthetist, emergency team or whoever is skilled and available to
assist.

Record the following information on the patient’s notes:

• Type of transfusion reaction.
• Duration of transfusion after which the reaction occurred.
• Volume, type and pack numbers of the blood products
transfused.

Draw the following samples and send them to the blood bank for
laboratory investigations:
A. Immediate post-transfusion blood samples (1 clotted and 1
anticoagulated; EDTA/Sequestrene) from the vein opposite the
infusion site for:
• Repeat ABO and RhD groups.
• Repeat Ab screen and crossmatch.
• Full blood count.
• Coagulation screen.
• Direct antiglobulin test.
• Urea.
• Creatinine.
• Electrolytes.
B. Blood culture in two special blood culture bottles (aerobic and
anaerobic).
C. Blood unit and giving set containing red cell and plasma residues
and arrange for urgent gram stain from blood unit.
D. First specimen of the patient’s urine following the reaction.

- 50 -
Complete a transfusion reaction report form and send it to the
blood bank along with previous samples.

Part I: 5.
See Annex 6 for a sample post-transfusion reaction investigation form.

Send the following to the blood bank for laboratory investigations

after the initial investigation of the reaction:
• Blood samples, 1 clotted and 1 anticoagulated
(EDTA/Sequestrene), taken from the vein contralateral to
that of the infusion site 12 hours and 24 hours after the
start of the reaction.
• The entire patient’s urine for at least 24 hours after the
start of the reaction.

Record the results of the investigations in the patient’s records for

future follow-up, if required.

- 51 -
I.6. Hospital Transfusion Committee (HTC)

An HTC is an essential component of a strategy to ensure the ACUB.

• The HTC should implement the national blood policy and the
guidelines mentioned in this handbook on the ACUB and monitor the
use of blood and blood products at the local level. It should have
authority within the hospital to determine hospital policy in relation
to transfusion and be able to resolve any problems that have been
identified.
• Within the hospital, information needs to be collected in a systematic
way in order to evaluate clinical blood use and adverse transfusion
reactions.
• Development of the HTC requires the involvement of personnel from
different departments, specialties and levels of the health care
system.

- 52 -
I.6.1. Members of the HTC
• Representative of the Hospital Administration: the HTC is best
headed by the hospital director. This will ensure the authorization

Part I: 6.
and implementation of any recommendations or proposed corrective
and preventive actions.
• Clinical Specialists: senior representatives of clinical departments
that prescribe blood in the hospital.
• Representative of the Hospital Blood Bank (HBB).
• Representative of the BTS: from the blood center that supplies blood
to the hospital.
• Representative from Pharmacy/Supply.
• A Hospital Administration and Finance Staff Member: responsible
for the supply of IV fluids, pharmaceuticals, medical devices and
sterile disposable equipment.
• Senior Nurse.
• Medical Records Staff Member.

- 53 -
I.6.2. Role of the HTC
The main functions of the HTC include:
• Monitoring safety, adequacy and reliability of the supply of blood,
blood components and IV fluids to the hospital.
• Estimating the blood requirements of the hospital.
• Developing systems, procedures and essential documents for the
implementation of the national guidelines for ACUB within the
hospital.
• Monitoring the implementation of guidelines through continuous
auditing.
• Liaising with the BTS to ensure the availability of required blood and
blood products at all times.
• Liaising with the relevant department to ensure a reliable supply of
IV replacement fluids and other alternatives to transfusion at all
times.
• Developing a hospital blood-ordering schedule.
• Developing hospital SOPs for all steps in the transfusion process.
• Promoting awareness through continuous education and training of
all hospital staff involved in transfusion.
• Monitoring the use of blood and blood components within the
hospital.
• Monitoring and investigating severe adverse effects or errors
associated with transfusion, taking any corrective or preventive
action required and reporting through the hemovigilance system to
the national committee on the ACUB.

- 54 -
I.7. Hemovigilance
At any time it should be possible to know

Part I: 7.
who received what from whom.
• Hemovigilance is the systematic monitoring of side effects and
adverse incidents throughout the transfusion chain from blood donors
to recipients, and all other activities which can lead to safer and more
effective use of blood components.
• Hemovigilance shall mean a set of organized surveillance procedures
relating adverse or unexpected reactions in donors or recipients, and
the epidemiological follow-up of donors.
• Hemovigilance is implemented through a system for monitoring,
reporting and investigating adverse transfusion reactions in order to
prevent their occurrence or recurrence.
• Hemovigilance has become an integral part of transfusion safety and
quality.
• Hemovigilance requires setting up an accurate documentation system
for every step in the transfusion chain from donor to recipient in
order to allow the tracing of any blood unit.
• This traceability is a shared responsibility between the blood bank
and the hospital, as both partners should share all information during
investigations of adverse transfusion reactions.
• A simple and effective reporting system should be set up in the
hospital. This system can be designed and implemented according to
local circumstances and followed by the HTC.
• This system should specify the staff responsible, forms used,
flowchart, action taken, etc.

- 55 -
I.8 Therapeutic Apheresis
Therapeutic apheresis is the separation and removal of that portion of a
patient’s blood which contains a putative pathogenic component. Machines
that can separate, collect and re-infuse the various blood fractions are used
for this procedure. These machines are called cell separators or apheresis
machines. The procedures are classified as follows:

A. Cytapheresis:
This includes procedures that remove erythrocytes, platelets,
lymphocytes or granulocytes.
Indications:
• Malaria.
• In management of complications of sickle-cell disease as red blood
cell exchange.
• In acute myeloid leukemia or chronic granulocytic leukemia,
therapeutic leucopheresis can be performed in blast crisis to treat
leucostasis.
• In patients with malignant platelet disorders and a risk of thrombosis
and hemorrhage (platelet count greater than 1,000 x 109/l),
plateletpheresis may be useful until chemotherapy is effective.

B. Plasma Exchange:
Plasma exchange is the removal of a large volume of plasma containing
pathogenic materials or antibodies causing acute disease or organ damage
and replacement by an appropriate fluid.
Indications:
• Hyperviscosity syndrome associated with:
o Hyperglobulinemia.
o Acute myasthenia gravis.

- 56 -
 o Guillain-Barre syndrome.
o Chronic relapsing inflammatory polyneuropathy.
o Goodpasteure’s syndrome.

Part I: 8.
o Cryoglobulinemia.
o TTP.
o Waldenstrom macroglobulinemia.
o Familial hypercholesterolemia.
o Immune complex vasculitis, e.g. SLE.
• Hemophilia with inhibitors can also benefit from plasma exchange.
• Poisons and drugs.
• RhD immunized pregnant women.
Procedure:
• The large amount of plasma removed must be replaced with colloid
or crystalloid.
• The commonly used fluids are albumin and FFP.
• In TTP, CDP is the fluid of choice.
• The usual practice is to exchange about 3-4 l of plasma during each
procedure, to be repeated daily or on alternate days until obtaining
the desired reduction.
• The procedure is an adjunct to the conventional treatment of the
underlying disease.

- 57 -
- 58 -
 Part II
Clinical Transfusion Practice

- 59 -
II.1 Anemia
Definition:
An Hb concentration in blood that is below the expected value, when
taking into consideration age, gender, pregnancy and altitude.

Anemia is also defined as a reduction in red cell mass, resulting in a

lowered Hb and Hct level, and leading to a decrease in the Oxygen-carrying
capacity of the blood.

The WHO established criteria to define anemia based on a normal Hb

level at sea level. These criteria are shown in Table 12.
Table 12: Classification of Anemia according to Hb Level
Gender Normal Hb (g/l) Anemic if Hb less than
Adult Males 130 - 170 130 (Hct 39%)
Non-pregnant Adult
120 - 150 120 (Hct 36%)
Females

The National Cancer Institute (NCI) and WHO have provided scales for
characterizing the severity of anemia based on Hb level. This is shown in
Table 13.
Table 13: Classification of Anemia according to Severity
Grade (Severity) NCI Scale WHO Scale
Normal, i.e.140 - 180 g/l
0 (None) for males 120 - 160 g/l for > 110 g/l
females
1 (Mild) 100 g/l - normal 95 - 109 g/l

2 (Moderate) 80 - 100 g/l 80 - 94 g/l

3 (Severe) 65 - 79 g/l 65 - 79 g/l

4 (Life Threatening) < 65 g/l < 65 g/l

- 60 -
Causes of Anemia:
There are many diseases and pathological situations that can lead to
anemia, but all of these situations fall under the following generic
categories:
1. Increased loss of blood cells.
2. Decreased production of normal RBCs.
3. Increased destruction of RBCs (hemolysis).
4. Increased demand for RBCs.

Clinical Manifestations of Anemia:

The rate at which anemia develops usually determines the severity of the
symptoms. Accordingly, anemia can be classified into:

A. Moderate Anemia:
No symptoms occur, especially when due to a chronic process. But it
reduces the patient’s ability to adjust to an acute event such as hemorrhage,
infection, or childbirth.

B. Severe Anemia:
Whether acute or chronic, it is an important factor in reducing the
patient’s tissue Oxygen supply to critical levels. In this situation, urgent
treatment is required and the need for transfusion should be assessed.
The overall Oxygen supply to body tissues depends on other factors than
Hb concetration. (for more details see II.2.)
Part II: 1.

Compensatory responses are physiological changes that aim to increase

Oxygen supply to tissues in response to the effects of anemia.

- 61 -
Management of Anemia:
• The treatment of anemia will vary according to the cause, rate of
development and degree of compensation to the anemia.
• Hb levels are used as thresholds for investigation and treatment but
NOT as indicators for transfusion.
• Transfusion is considered only if the anemia is severe enough to
reduce Oxygen supply to tissues so that the supply is inadequate
for the patient’s needs.

- 62 -
II.1.1. Chronic (Compensated) Anemia
In chronic blood loss, small amounts of blood are lost from circulation
over a long period of time and normovolemia is maintained with no or few
clinical signs.

Treatment:
• Exclude the possibility of a hemoglobinopathy.
• Identify the cause of the anemia and correct any identified cause.
• Give medical treatment according to the cause of the anemia.

II.1.2. Severe (Decompensated) Anemia

Causes of decompensation:
• Heart or lung disease that limits the compensatory responses.
• Increased demand for Oxygen from:
o Infection.
o Pain.
o Fever.
o Exercise.
• Acute reduction in Oxygen supply:
o Acute blood loss and/or hemolysis.
o Pneumonia.

Signs of decompensation:
• Changes in mental state.
Part II: 1.

• Diminished peripheral pulses.

• Congestive heart failure.
• Hepatomegaly.
• Poor peripheral perfusion (capillary refill greater than 3 seconds).

- 63 -
Treatment of severe (decompensated) anemia:
• Treat bacterial chest infection aggressively.
• Give Oxygen by mask.
• Correct the fluid balance so as not to cause cardiac failure.
• Use PRCs rather than WB to minimize the volume and the oncotic
effect of the infusion. Administer PRCs over 2-4 hours with a
rapidly acting diuretic (e. g. Frusemide 40 mg IM).
• Reassess the patient before further transfusion.
• Relieve the clinical condition rather than raise the Hb level.

N.B.: One unit of PRCs raises the Hb level in an adult

by about 0.7-1 gm/dl.

The aim of red blood cell transfusion is to give the patient

sufficient Hb to relieve hypoxia and NOT to restore the
Hb level to normal.

- 64 -
II.2. Hypovolemia and Massive Transfusion
In cases of major trauma and surgery, blood volume should be
maintained at all times. Fluid replacement will prevent hypovolemia with its
serious complications (see Tables 4 and 5 for available IV fluids).
The decision for fluid replacement and transfusion will be based on
careful assessment of:
• Volume of blood loss.
• Rate of blood loss (actual and anticipated).
• Patient’s clinical assessment.

The ability of a patient to compensate for a reduction in Oxygen supply will

be limited by:
• Evidence of cardiorespiratory disease.
• Treatment with drugs such as beta blockers.
• Pre existing anemia.
• Extremes of age.

In case of healthy individuals:

• Acceptable loss of blood volume is 30%
• Lowest acceptable Hb or Hct is 9g/dl (Hct 27%)

In case of average clinical condition:

• Acceptable loss of blood volume is 20%
• Lowest acceptable Hb or Hct is 10g/dl (Hct 30%)

In case of poor clinical condition:

Part II: 2.

• Acceptable loss of blood volume is less than 10%

• Lowest acceptable Hb or Hct is 11g/dl (33%)

- 65 -
Hypovolemic shock:
Hypovolemic shock refers to a medical or surgical condition in which
rapid blood or fluid loss results in multiple organ failure due to inadequate
perfusion. Most often, hypovolemic shock is secondary to rapid blood loss
(hemorrhagic shock).
Oxygen delivery to tissues is defined as the product of cardiac output and
arterial Oxygen content.

Cardiac output equals to the product of stroke volume by heart rate.

Stroke volume depends on:

• Preload, which is the volume and pressure of blood in the ventricle
at the end of diastole.
• Myocardial contractility.
• Afterload, which depends on peripheral vascular resistance.

Arterial Oxygen content =

Oxygen saturation x Hb concentration x 1.39 x 0.0031 x arterial
Oxygen pressure.

1.39 = maximum ml of Oxygen 1 g of Hb can carry when fully saturated.

0.0031 = Oxygen solubility in plasma.

Normal arterial oxygen saturation is 97%.
Normal arterial oxygen pressure = 12-15 kPa.

- 66 -
So Oxygen delivery to tissues can be improved by many factors other
than transfusing PRCs:
• Increasing arterial Oxygen saturation and arterial Oxygen pressure.
• Increasing the preload by proper hydration.
• Increasing cardiac contractility.
• Decreasing the afterload by hemodilution or vasodilatation.

Part II: 2.

- 67 -
When to Transfuse:
• Blood losses up to 40% can be managed adequately by fluid
replacement, either through a crystalloid solution or a mixture of
crystalloid and colloid solution. This treatment will increase the
preload, stretch the myocardium to increase contractility and
decrease the peripheral vascular resistance by hemodilution. Cardiac
output increases to compensate for the drop in Oxygen content and
keeps the Oxygen delivery stable.
• RBC transfusion should not be dictated by a single Hb
measurement. A transfusion is rarely indicated for Hb levels of more
than 10 g/dl but is usually indicated for an acute loss to less than 6
g/dl.
• The gray area, between 6-10 g/dl Hb, is easily compensated for in
otherwise healthy patients, especially in obstetric patients as they
already have an increased blood volume.
• The human body responds to acute hemorrhage by activating four
major physiological systems: the hematological, cardiovascular,
renal, and neuro-endocrine systems.

- 68 -
Table 14: Classification of Hypovolemia and Shock in Adults
Class I Class II Class III Class IV
Mild Progressive Severe End Stage
Blood Loss, up to 750 750-1,500 1,500-2,000 2,000 or more
in ml
Blood Loss,
up to 15 15-30 30-40 40 or more
% of BV
Pulse/Minute Normal >100 >120 140 or higher
Blood
Normal Normal Decreased Decreased
Pressure
Pulse
Pressure Normal Decreased Decreased Decreased
(mm Hg)
Capillary
Normal Prolonged Very Prolonged Absent
Refill Test
Respiration
Normal 20-30 30-40 > 40
per min
Urine
30 or more 20-30 5-10 Negligible
Output, ml/hr
CNS (Mental Alert/Slightly Comatose/
Anxious Confused
Status) Anxious Unconscious
Fluid
Crystalloid + Crystalloid +
Replacement Crystalloid Crystalloid
Blood Blood
(3:1 Rule)

Part II: 2.

- 69 -
Management of Hypovolemic Shock:
Targets:
1. Maximize Oxygen delivery - completed by ensuring adequacy of
ventilation, increasing Oxygen saturation of the blood, and
restoring blood flow.
2. Control further blood loss.
3. Control fluid resuscitation. The patient’s disposition should also be
quickly and appropriately determined.
What to do?
• Assess the patient’s airway immediately upon arrival and
stabilize if necessary, as well as the depth and rate of respirations
and breathing sounds.
• Start two short large bore IV cannulae.
• Once the IV access is obtained, initial fluid resuscitation is to be
performed.
• Give initial fluid bolus of 30 ml/kg of crystalloid or 10-20 ml/kg
of colloid over 5 minutes to any patient showing signs of more
than 15% blood loss (Class II hypovolemia and above).
• Where possible, the fluid should be warmed to prevent further
hypothermia.
• Assess the patient’s response to guide further fluid/blood
infusion.
• If urgent transfusion is likely to be life saving (Class IV shock)
do not wait for fully crossmatched blood but use un-
crossmatched blood of the same ABO and Rh group of the
patient, or un-crossmatched group O negative RBCs.

- 70 -
 A Simple Method for Determining Resuscitation Volume (RV)

Follow the Exact Sequence Description

Blood volume in adults equals

1. Estimate normal blood volume.
70 ml/kg body weight.

2. Estimate % loss of blood volume. ACS classification (see II.2.).

3. Calculate volume deficit (VD). VD = BV x % loss.

WB: RV = VD
4. Determine resuscitation volume
Colloids: RV = 1.5 x VD
(RV).
Crystalloids: RV = 4 x VD

Massive Blood Transfusion:

Definition:
Massive blood transfusion is the replacement of blood loss with stored
blood equivalent to or greater than the patient’s total blood volume in less
than 24 hours (blood volume in adults = 70 ml/kg body weight). Massive
blood transfusion is usually required in cases of acute hemorrhage in
obstetric, surgical and trauma patients.
Part II: 2.

Morbidity and mortality tend to be high with massive blood transfusion

not because of the large volumes infused, but in many cases, because of the
initial trauma and the tissue and organ damage secondary to hemorrhage
and hypovolemia.

- 71 -
Complications and management:
• Acidosis: due to red cell metabolism during blood storage. The body
can easily neutralize this acid load.

• Hyperkalemia: extracellular Potassium increases during the storage

of blood, but this is rarely of clinical significance in adults.

• Citrate Toxicity or Hypocalcemia: is a rare problem but reduction in

the ionized Calcium level, together with hypothermia and acidosis can
cause a reduction in cardiac output, bradycardia and arrhythmias.
After transfusion, the citrate is usually rapidly metabolized to
bicarbonate. If there is clinical or biochemical evidence of a reduced
ionized Calcium level, Calcium salts are given in the form of Calcium
chloride.

• Depletion of Fibrinogen and Coagulation Factors: in particular F V

and F VIII. If the PT is prolonged, FFP is given in a dose of 15 ml/kg
body weight. If Partial Thromboplastin Time (PTT) is prolonged,
cryoprecipitate is given (10-15 ml). It contains F VIII and fibrinogen.

• Depletion of Platelets: platelet function is rapidly lost during storage

of blood. Platelet concentrates should only be given in the following
conditions:
o Patient shows signs of microvascular bleeding, i.e. bleeding and
oozing from mucous membranes, wounds, raw surfaces and
catheter sites.
o Patient with platelet count below 50 x 103/l and signs of active
bleeding.
o DIC: see II. 3. 1.

• Hypothermia: a fall in body temperature of a patient can cause

several unwanted effects such as:

- 72 -
 1. Impairment of normal compensatory responses to
hypovolemia.
2. Increase in bleeding during surgery.
3. Increase in post-operative Oxygen demand as
normothermia becomes re-established. This may
lead to hypoxia.
4. Increase in wound infection.

To avoid hypothermia, the following points are essential:

1. Keep the patient warm.
2. Warm the blood and IV fluids before transfusion
(using specialized devices).

Annex 7 shows an algorithm for massive transfusion.

Part II: 2.

- 73 -
II.3. Coagulation and Bleeding Disorders
II.3.1 Disseminated Intravascular Coagulopathy (DIC)
Definition:
DIC is a condition resulting in the activation of both the coagulation and
the fibrinolytic systems, leading to consumption of coagulation factors,
fibrinogen and platelets with microvascular thrombi in the circulation.
Clinical Features:
The clinical picture ranges from major hemorrhage, with or without
thrombotic complications, to a clinically stable state that can be detected
only by laboratory testing.
In cases of severe DIC, there is excessive, uncontrolled bleeding. The
lack of platelets and coagulation factors causes hemorrhage, bruising and
oozing from venepuncture sites.
Microvascular thrombi may cause multiple organ dysfunction leading
to respiratory distress, coma, renal failure and jaundice.
Laboratory Findings:
• Prolonged PT and PTT due to reduced coagulation factors.
• Prolonged TT (particularly helpful in the diagnosis of DIC).
• Decreased platelet count.
• Decreased fibrinogen level.
• Increased FDPs (using latex assay or D dimers assay which
identifies only cross-linked FDPs indicating fibrinolysis).

- 74 -
If the lab tests are not available, use the following Weiner’s test (clot
stability test):
• Take 2-3 ml of venous blood in a clean plain GLASS test tube (10
x 75 mm).
• Hold the tube in a closed fist to keep it warm (i.e. body
temperature).
• After 4 minutes, tip the tube slowly to see if a clot is forming. Then
tip it again every minute until the blood clots and the tube can be
turned upside down.
• The clot will normally form between 4-11 minutes, but in cases of
DIC blood will remain fluid well beyond 15-20 minutes.
Management:
• If DIC is suspected, do not delay treatment while waiting for the
results of coagulation tests.
• Rapid treatment of the cause or underlying condition is imperative.
• Give supportive care: fluids, vasopressor agents, renal, cardiac or
ventilatory assistance.
• Monitor the patient by: PTT, PT, TT, platelet count, and fibrinogen
level.
Transfusion in DIC:
• If PT or PTT is prolonged and the patient is bleeding, give 15
ml/kg of FFP (usually 4-5 packs in adults).
• If the fibrinogen level is low, give cryoprecipitate (8-10 packs in
adults).
Part II: 3.

• If the platelet count is low (< 50 x 109/l) and the patient is

bleeding, give platelet concentrate (4-6 RDP packs in adults).
N.B.: Platelets should not be given in the early stages of DIC.
Fresh WB should not be used except if blood
components are not available.

- 75 -
II.3.2. Coagulation Disorders and Surgery
• Undiagnosed and untreated coagulation disorders in surgical patients
may result in excessive operative blood loss, uncontrolled hemorrhage
and death of the patient.
• It is therefore essential to have an accurate pre-operative history about
any unusual bleeding tendency of the patient and/or members of
his/her family, together with a drug history.
• Bleeding during or after surgery is usually due either to surgical
intervention where re-operation will be necessary or hemostatic
problems, most commonly:
o Massive transfusion with dilution of platelets and coagulation
factors.
o DIC (thrombocytopenia and hypofibrinogenemia).
• Laboratory investigations for evaluation of bleeding in surgical
patients are: PT, PTT, CBC, platelet count, and BT.
• Drugs such as Aspirin and Non-Steroidal Anti-Inflammatory Drugs
(NSAIDs) which interfere with platelet function should be stopped 10
days prior to surgery.
• In patients treated with anticoagulants, either Warfarin or Heparin, the
INR should be less than 2 before the start of surgery.
• Patients with congenital coagulation disorders should start treatment
1-2 days prior to surgery and continue for 5-10 days with regular
assessment in the pre-operative period to detect any bleeding.
• Platelet transfusion should be given if there is clinical evidence of
severe microvascular bleeding and the platelet count is below 50-100
x 109/l.

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Preparation of the Anticoagulated Patient for Surgery:

PATIENTS FULLY ANTICOAGULATED WITH WARFARIN

Elective Surgery
1. Stop Warfarin three days pre-operatively and monitor INR daily.
2. Give Heparin by infusion or SC when INR is < 2.0.
3. Stop Heparin 6 hours pre-operatively.
4. Check PTT and INR immediately prior to surgery.
5. Commence surgery if PTT and INR are < 2.0.
6. Restart Warfarin as soon as possible post-operatively.
7. Restart Heparin at the same time and continue until INR is in the therapeutic
range.
Emergency Surgery
1. Give Vitamin K in a dose of 0.5-2.0 mg by slow IV infusion.
2. Give 15 ml/kg of FFP. This dose may need to be repeated to bring coagulation
factors to an acceptable range.
3. Check INR immediately prior to surgery.
4. Commence surgery if PTT and INR are < 2.0.
PATIENTS FULLY ANTICOAGULATED WITH HEPARIN
Elective Surgery
1. Stop Heparin 6 hours pre-operatively.
2. Check PTT immediately prior to surgery.
3. Commence surgery if PTT is < 2.0.
4. Restart Heparin as soon as appropriate post-operatively.
Emergency Surgery
Consider reversal with IV Protamine sulphate. 1 mg of Protamine neutralizes 100
Part II: 3.

IU Heparin.
PATIENTS RECEIVING LOW-DOSE HEPARIN
It is rarely necessary to stop low-dose Heparin injections used to prevent deep
vein thrombosis and pulmonary embolism prior to surgery.

- 77 -
Guidelines for Neuraxial (Epidural and Spinal Anesthesia) Block in
Patients Taking Drugs Affecting Hemostasis:
• Aspirin and NSAIDs:
o No contraindication.
• Clopidogrel: Stop 7 days preoperatively.
• Unfractionated Heparin:
o SC: give 4 hours before or > 1 hour after block.
o IV: stop 4 hours before block, give > 1 hour after block,
remove catheter 2-4 hours after dose.
• Low molecular weight Heparin: Wait 12 hours after dose or give
drug after block. Wait 24 hours after therapeutic dose.
• Warfarin: INR < or = 1.5.

II.3.3. Bleeding Disorders:

Recognizing, and correctly diagnosing and treating a patient with a
bleeding disorder has the following effects:
• Influences the timing and type of elective surgery.
• Reduces the need for transfusion.
• Avoids the risks to the patient due to bleeding.
A bleeding tendency may be due to:
• Congenital (inherited) disorder of blood vessels.
• Platelet defects.
• Deficiency of coagulation factors.
• Use of pharmaceutical drugs.
• Trauma.
• Hemorrhage.
• Obstetric complications.
• Nutritional deficiency.

- 78 -
 Table 15: Laboratory Investigations: Typical Results

Fibrinolytic Therapy

Massive Transfusion
Thrombocytopenia

von Willebrand’s

Hemophilia A

Hemophilia B
Liver Disease

Warfarin
Heparin

Disease
DIC
Platelet Count  N/  N N/ N/ N N N 
PT N N   N   N N 
APTT N    N/     
- 79 -

TT N    N  N N N N/
Fibrinogen
N N   N  N N N N/
Concentration
Fibrin Degradation
N N   N N/ N N N N/
Products

N = Normal  = High  = Low

79
Part II: 3.
II.3.3.1. Congenital Bleeding Disorders
A. Hemophilia A:
Hemophilia A is caused by an inherited deficiency of coagulation Factor
VIII. Table 16 illustrates the dose of F VIII in acute bleeding cases of
hemophilia A.

Table 16: Dose of Factor VIII and Alternatives for Treatment of

Hemophilia A
Supplied as
Severity of Bleeding Dosage F VIII concentrate Cryoprecipitate (80-
(500 IU/bottle) 100 IU/pack)
Mild Bleeding: 14 IU/kg 1-2 bottles (adult) 1 pack/6 kg
Nose, Gums, etc.
Moderate Bleeding:
Joints, Muscles, GIT, 20 IU/kg 2-4 bottles (adult) 1 pack/4 kg
Surgery
Major Bleeding: 40 IU/kg 4-6 bottles (adult) 1 pack/2 kg
Cerebral

Prophylaxis for Major 60 IU/kg 6-10 bottles 1 pack/1 kg

Surgery

- 80 -
• For mild, moderate or severe bleeding, repeat dose every 12 hours if
bleeding persists or swelling is increasing. With more severe
bleeding, it is usually necessary to continue treatment with half of the
total daily dose every 12 hours for 2-3 days or occasionally for
longer periods.
• For prophylaxis for major surgery, start therapy 8 hours before
surgery. Continue therapy every 12 hours for 48 hours post-
operatively. If no bleeding occurs, scale down gradually over the
next 3-5 days.
• As an adjunct to factor replacement in mucosal or gastrointestinal
bleeding and surgery, give fibrinolytic inhibitor tranexamic acid
(orally), 500-1,000 mg, 3 times/day. Do not use for hematuria.
• In an emergency, use FFP to treat bleeding in hemophiliacs (give 3
packs initially) if none of the above is available.
• Careful assessment of the patient’s fluid intake is important to avoid
fluid overload when using FFP or large doses of cryoprecipitate.
• Avoid anti-platelet drugs such as Aspirin and NSAIDs.
• Do not give IM injections.
• Administer coagulation factor concentrates to treat bleeding episodes
as quickly as possible.
• For hemarthrosis, give strong analgesics, ice packs and
immobilization. Never incise swellings in hemophiliacs.
Part II: 3.

• Start physiotherapy early to minimize loss of joint function.

- 81 -
• DDAVP releases stored endogenous Factor VIII and vWF, so it may
be useful in mild and moderate hemophilia A. IV Minirin sometimes
helps in mild hemophiliacs in the proper dosage.
• EACA is useful in minimal gum bleeding.

- 82 -
B. Hemophilia B:
Hemophilia B is caused by an inherited deficiency of coagulation Factor
IX.

Table 17: Dose of Factor IX and Alternatives for Treatment of

Hemophilia B
Supplied as
Severity of Bleeding Dose Factor IX concentrate FFP or CDP
(500 IU/bottle) (80-100 IU/pack)
Mild Bleeding 15 IU/kg 2 bottles (adult) 1 pack/15 kg
Major Bleeding 20-30 IU/kg 3-6 bottles (adult) 1 pack/7.5 kg

N.B.:
• Repeat in 24 hours if bleeding continues.
• F VIII concentrate and cryoprecipitate are not useful for hemophilia
B, so accurate diagnosis is essential.
• As an adjunct to replacement therapy: tranexamic acid (orally), 500-
1,000 mg, 3 times/day, as for hemophilia A.

C. von Willebrand Disease:

vWF is a protein involved in platelet adhesion, both to other platelets
and to the sub-endothelium. It also acts as a carrier protein for F VIII.
Deficiency of vWF is inherited as an autosomal dominant condition
affecting both males and females.
Part II: 3.

The major clinical manifestation is mucocutaneous bleeding in the form

of:
• Epistaxis.
• Easy bruising.
• Menorrhagia.

- 83 -
 • Bleeding after tooth extraction.
• Post-traumatic bleeding.

Management of von Willebrand disease:

Treatment aims to normalize BT either by increasing endogenous vWF
levels by DDAVP or by replacing vWF with an intermediate purity F VIII
which contains some vWF, or by cryoprecipitate which also contains vWF.
• DDAVP: 0.3-0.4 mg/kg IV lasts 4-8 hours and obviates the need to
use plasma products. The dose can be repeated every 24 hours but the
effect is reduced after some days of treatment. F VIII products are
reserved for patients non-responsive to DDAVP.
• Cryoprecipitate.
• In Type IIb with thrombocytopenia do not give platelet transfusion or
DDAVP. Give only F VIII.
• In Type III when vWF is deficient, it should be replaced with F VIII
which is also deficient.

II.3.3.2. Acquired Bleeding Disorders:

A. DIC: See Chapter II.3.1.
B. Disorders of Vitamin K-Dependent Coagulation Factors:
Vitamin K is a fat-soluble vitamin found primarily in green vegetables
and liver. It is a co-factor for the synthesis of F II, VII, IX, and X which
takes place in the liver.

- 84 -
Common causes of deficiency of Vitamin K-dependent factors include:
• Coumarin anti-coagulants (Warfarin). Some drugs such as certain
antibiotics may cause bleeding by displacing Warfarin bound to
plasma proteins.
• Vitamin-K deficiency due to inadequate diet or malabsorption.
• Liver disease, leading to decreased production of F II, VII, IX, and
prolonged PT is usually a feature of severe liver disease.

Management of Vitamin K deficiency:

• Remove the underlying cause of Vitamin K deficiency.
• Treat malabsorption or dietary deficiency.
• Stop anticoagulants.
• Replace coagulation factors with FFP, platelet concentrates and
fibrinogen as necessary.
• Reverse Warfarin with Vitamin K IV if the patient is bleeding and
the PT is prolonged (INR >4.5). Doses of Vitamin K exceeding 1
mg may make the patient refractory to additional Warfarin for up
to 2 weeks.

N.B.: If anticoagulation is still needed, consider doses of 0.1-0.5 mg.

Part II: 3.

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II.3.3.3. Disorders of Platelets
Platelet disorders are classified into:
1) Quantitative Platelet Disorders (thrombocytopenia)
2) Qualitative Platelet Disorders (thrombocytopathy).

Platelet Alloantibodies:
Over two thirds of recipients receiving multiple platelet
transfusions from random donors become alloimmunized to HLA
and/or platelet-specific antigens. Some recipients become
“refractory”, i.e. the expected platelet increment will not be
achieved because of rapid immune destruction of the transfused
platelets, usually by antibodies to HLA and rarely by antibodies to
platelet-specific antigens.

Diagnosis of Platelet Refractoriness:

• Decrease response to platelet transfusion in the absence of fever,
infection, severe hemorrhage, splenomegaly or DIC.
• Failure of 2 consecutive transfusions to give a corrected increment
of greater than 7.5 x 109/l one hour after transfusion.
• Lymphocytotoxicity test (donor lymphocytes mixed with recipient
serum) can confirm anti-HLA antibodies in the patient’s serum.
• Other immunological tests: platelet imunofluorescence or ELISA
can diagnose the presence of anti-platelet specific antigens in the
patient’s serum.

- 86 -
Prevention of Platelet Alloimmunization:
• Rationalize the use of platelets in transfusion.
• Use SDPs from selected donors. Limit donor exposure with
cooperation of the blood bank.
• Use leucocyte-depleted platelet concentrates (platelet concentrates
that contain less than 5 x 108 white cells), which is the minimum
number of WBCs required for immunization against HLA
antigens.

Management of a Patient with Platelet Alloantibodies:

• Consider HLA matched platelets.
• Administer high-dose IV Igs.

Part II: 3.

- 87 -
II.4. Transfusion Practice in Different Clinical Situations

II.4.1. Transfusion in Pediatrics and Neonates:

II.4.1.1. Pediatric Anemia:

According to WHO criteria, infants and children are considered to have
anemia if their Hb concentration falls below the levels shown in Tables 18
and 19.

Table 18: Mean Hb Values (g/dl) in Term and Pre-term

Neonates and Their Changes during the First Month of Life
Term Premature Infants Small Premature Infants
Week
Infants (1200-1500 g) (< 1200 g)
0 17 16.4 16
1 18.8 16 14.8
3&4 15.9 13.5 13.4

Table 19: Normal Blood Indices beyond the Neonatal Period

Expressed as Mean ± SD
MCV
Age Hb (g/dl) Hct (%)
(Femtolitres)
1 Month 14 ± 4 43 ± 12 104 ± 19
2 Months 11.5 ± 2.5 35 ± 7 96 ± 19
3-6 Months 11.5 ± 2 35 ± 6 91 ± 17
1 Year 12 ± 1.5 36 ± 3 76 ± 8
2-6 Years 12.5 ± 1 37 ± 3 81 ± 6
6-12 Years 13.5 ± 2 40 ± 5 80 ± 9
12-18 Years 14 ± 2 42 ± 6 89 ± 11

- 88 -
Critical Levels that Indicate Blood Transfusion:
Infants within the first 4 months:
• Hb < 13.0 g/dl in severe cardiac disease and severe pulmonary
disease.
• Hb < 10.0 g/dl in moderate pulmonary disease and major surgery.
• Hb < 8.0 g/dl in symptomatic chronic anemia and marrow failure.

Children and adolescents:

• Acute loss > 25% circulating blood volume.
• Hb < 8.0 g/dl in the peri-operative period.
• Hb < 3.0 g/dl and severe cardiopulmonary disease.

Clinical Features of Anemia in Children:

Compensated anemia:
A child with well-compensated anemia may have:
• Raised respiratory rate.
• Increased heart rate.

But will be alert, able to drink and breastfeed, have normal quiet breathing
with abdominal movement and with minimal chest movement.
Decompensated anemia:
Causes of decompensation:
Part II: 4.

• Increased demand for Oxygen:

o Infection.
o Pain.
o Fever.
o Exercise.

- 89 -
 • Further reduction in Oxygen supply:
o Acute blood loss.
o Pneumonia and other pulmonary pathologies that may lead to
respiratory failure such as RDS, air leaks and lung hypoplasia.
Early signs of decompensation:
• Increased effort to breathe as shown by labored, rapid breathing
with intercostal, subcostal and suprasternal retractions/recessions,
increased use of abdominal muscles for breathing, flaring of
nostrils.
• Difficulty with feeding.
Signs of acute decompensation:
• Forced expiration (grunting)/respiratory distress.
• Alteration of level of consciousness.
• Diminished or absent peripheral pulses.
• Congestive cardiac failure.
• Hepatomegaly.
• Poor peripheral perfusion (capillary refilling time greater than 3
sec.).

Acute decompensated anemia needs urgent treatment, as there

is a high risk of death due to insufficient Oxygen-carrying
capacity. Extra Oxygen supply is a top priority.

- 90 -
Red Cell Transfusion:
• A red cell transfusion is preferable to WB for a patient at risk for
circulatory overload.
• 10-15 ml/kg of PRCs results in a 7-0% increase in Hct value
(increases Hb concentration by approximately 2-3 g/dl unless there is
continued bleeding or hemolysis).
• Most patients tolerate infusion rates up to 10 ml/kg/hr.
• Children with volume intolerance due to high output heart failure
should be transfused gradually (5-10 ml/kg over 4-6 hours +
diuretics). Give Furosemide in doses of 1 mg/kg by mouth or 0.5
mg/kg by slow IV injection to a maximum dose of 20 mg/kg if the
patient is likely to develop cardiac failure and pulmonary edema. Do
not inject it into the blood pack.
• If rapid correction is necessary but limited by fluid intolerance, partial
exchange transfusion is indicated. WB is removed in small aliquots
and replaced with equal volumes of RBCs.
• Use a pediatric blood pack and control the rate and volume of
transfusion.
• Monitor during the transfusion for signs of: cardiac failure, fever,
respiratory distress, tachypnea, hypotension, acute transfusion
reactions, shock, hemolysis (jaundice and hepatosplenomegaly) and
bleeding due to DIC.
• Re-evaluate the patient’s Hb and/or Hct and clinical condition 24
hours after transfusion.
• If the patient is still anemic with clinical signs of hypoxia or a
critically low Hb level, give a second transfusion of 5-10 ml/kg of
Part II: 4.

PRCs or 10-20 ml/kg of WB.

- 91 -
Special Considerations in Neonatal Transfusion:
1- Infants have a long post-transfusion life expectancy, so they are
more likely to suffer from delayed adverse transfusion reactions as
opposed to HCV infection.
2- The recognition of variables in hematological parameters in the
pediatric age group will prevent unnecessary laboratory testing and
will reduce the need for transfusion.
3- If transfusion is necessary, give the appropriate dose and blood
component to make the child clinically stable.
4- The prevention and early medical treatment of anemia can reduce
the need for pediatric and neonatal transfusion.
5- Electrolyte content of blood components and IV fluids given to the
pediatric patient should be considered while calculating the total
electrolyte intake.
6- Potassium level increases in stored blood. This increase is
potentiated by irradiation. This problem is especially clinically
significant in cases of massive or exchange transfusion.

See I.4. for details of procedures and precautions.

- 92 -
Table 20: Selecting Blood Components for Neonatal Transfusion
Product Indications Special Requirements
WB Exchange transfusion for: Fresh blood (< 7 days) is not
• HDN necessary in exchange
• Severe neonatal sepsis transfusion for HDN, but it is a
must in exchange transfusion for
severe neonatal sepsis
PRCs Top up transfusion to raise Hb Small dose unit (pediatric pack
concentration in symptomatic chronic from single donation) to
anemia; often due to blood sampling in minimize exposure to different
sick premature infants donors
FFP • Bleeding tendencies, only when a
safer virus-inactivated product is
unavailable
• For infusion or exchange transfusion
treatment of TTP or HUS
Specially- • Intrauterine transfusion Avoid GvHD by:
Processed • Risk of GvHD is greater in • Irradiate: 25 Gy.
Cellular premature infants • Do not use donation from
Components • Risk of GvHD is greater if donor is a blood relative.
blood relative Use leucocyte-depleted cellular
components, to prevent CMV
infection.

Part II: 4.

- 93 -
II.4.1.2. Bleeding and Clotting Disorders:

A. Congenital Disorders:
See II.3.3.1. for hemophilia A, hemophilia B and von Willebrand
disease.

B. Acquired Disorders:
Vitamin K deficiency in neonates:
• An affected infant has a prolonged PT and PTT while platelets and
fibrinogen levels are normal. Treatment of bleeding as a result of
deficiency of Vitamin K dependent coagulation factors is by
parenteral 1-5 mg Vitamin K.
• Transfuse FFP or fresh WB only when there is evidence of
decompensated anemia or to correct a significant bleeding tendency.
• Late onset disease (more than 1 week after birth) is often associated
with malabsorption of Vitamin K and/or liver disease. It is treated
with oral water-soluble Vitamin K.

Thrombocytopenia:
• A normal neonate’s platelet count is 80-450 x 109/l. After one week
of life, the child reaches adult levels of 150-400 x 109/l. Platelet
counts below this level are considered to be low.
• Treatment of thrombocytopenia varies according to the cause.
Idiopathic thrombocytopenic purpura is usually self-limited but can be
treated with gamma globulin and corticosteroids.
• Platelet transfusion is indicated if life-threatening hemorrhage occurs,
especially in neonates.

- 94 -
Platelet transfusion for bleeding due to thrombocytopenia:
The goal of platelet therapy is to control or stop bleeding. The clinical
response is more important than the platelet count. Table 21 shows the
transfusion of platelet concentrate in pediatrics and neonates.

Table 21: Transfusion of Platelet Concentrate in Pediatrics and Neonates

Dose of Platelet
Patient’s
Concentrate Volume Platelet Content
Weight
(RDP)

Up to 15 kg 1 unit 30 - 50 ml* 60 x 109/l

15 - 30 kg 2 units 60 - 100 ml 120 x 109/l
> 30 kg 4 units 120 - 400 ml 240 x 109/l
* For small infants, the blood bank may remove part of the plasma before transfusion

Part II: 4.

- 95 -
Critical Levels for Neonatal and Pediatric Platelet Transfusion:

Infants within First 4 Months of Life:

Platelets < 100 x 109/l with bleeding

Platelets < 50 x 109/l non-bleeding, but subjected to invasive procedure
Platelets < 20 x 109/l non-bleeding and clinically stable
Platelets < 100 x 109/l non-bleeding and clinically unstable

Children and Adolescents:

Platelets < 50 x 109/l and bleeding

Platelets < 50 x 109/l non-bleeding, but subjected to invasive procedure
Platelets < 20 x 109/l non-bleeding with marrow failure with additional
hemorrhagic risk.
Platelet count normal but with defective functions, bleeding or invasive
procedure.

- 96 -
II.4.1.3. Guidelines for Neonatal Exchange Transfusion

Healthy term infants may tolerate serum bilirubin levels of 25 mg/dl. The
goal of therapy is to prevent the concentration of indirect bilirubin from
reaching neurotoxic levels.

A- Indications of neonatal exchange transfusion:

• Hemolytic Disease of the Newborn (HDN): fetal red blood cells can
enter the maternal circulation throughout pregnancy but this occurs
mainly during delivery and placental separation. If the mother red
cells are lacking one antigen that is present on fetal red cells from the
father, the mother will produce IgG antibodies against this specific
Ag. These antibodies can cross the placenta and cause hemolysis of
fetal red cells and hyperbilirubinemia. The most severe clinical
condition is caused by RhD Ag, but ABO Ags and RhC may be also
implicated for less severe cases of HDN.
• Sickle cell crisis.
• G6PD deficiency.
• Symptomatic polycythemia.

B- Calculations for Neonatal Exchange Transfusion:

• Partial Exchange Transfusion for Treatment of Symptomatic
Polycythemia:
Replace removed blood volume with normal saline or 5% albumin.
Volume to be exchanged (ml) =
Part II: 4.

Estimated blood volume x (Patient’s Hct - desired Hct)

P Patient’s Hct

The volume exchange is usually around 20 ml/kg. The exchange transfusion

should be performed in 10 ml aliquots.

- 97 -
 • Two-volume Red Cell Exchange Transfusion for Treatment of Sickle-
cell Crisis and Neonatal Hyperbilirubinemia:
Replace calculated blood volume with red cells suspended in 5% human
albumin.
Volume to be exchanged (ml) =
Estimated blood volume x (Patient’s Hct x 2)
Hct of transfused unit
N.B.: Hct of transfused blood:
• WB 35-45%
• PRCs 55-75%

For simplification: exchange transfusion with double the patient’s blood

volume.

C- Transfusion Procedures and Precautions:

• Nothing per mouth during and at least 4 hours after exchange
transfusion. Empty the stomach if the infant was fed within 4 hours of
the procedure.
• Closely monitor vital signs, blood sugar and temperature. Have
resuscitation equipment ready.
• For a neonate, umbilical and venous catheters inserted by sterile
techniques, may be used (blood is drawn out of the arterial catheter
and infused through the venous catheter). Alternatively, two
peripheral lines could be used.
• Pre-warm blood only if a blood warmer device is available. Do not
improvise by using a water bath.
• Exchange 10 ml increments in a full-term infant and smaller volumes
for smaller less stable infants. Avoid sedimentation in the blood unit.

- 98 -
• Withdraw and infuse alternatively blood 2-3 ml/kg/min to avoid
mechanical trauma to the patient and donor cells.
• Give 1-2 ml of 10% Calcium gluconate solution IV slowly for ECG
evidence of hypocalcemia (prolonged Q-T intervals). Flush tubing
with normal saline before and after Calcium infusion. Observe for
bradycardia during infusion and/or arrhythmias.
• To complete two-volume exchange, transfuse 170 ml/kg for a full-
term infant and not less than 170-200 ml/kg for a pre-term infant.
• Send the last aliquot drawn to the laboratory for determination of Hb
or Hct, blood smear, glucose, bilirubin, Potassium, Calcium and group
and match.
• Prevent hypoglycemia after exchange transfusion by continuing
infusion of glucose-containing crystalloid.
• When exchange transfusion is performed to treat HDN, the transfused
red cells must be compatible with the mother’s serum since the
hemolysis is caused by maternal IgG antibodies that cross the placenta
and destroy the fetal red cells.
• The neonate should receive phototherapy and supportive treatment.
Treatment should be initiated promptly, as jaundice may lead to
kernicterus.
• A two-volume exchange (approximately 170 ml/kg) is the most
effective in removing bilirubin.
Part II: 4.

• If the bilirubin rises again to dangerous levels, a further two volume

exchange should be performed.

- 99 -
D- Complications of Exchange Transfusion:
1. Cardiovascular:
• Thromboemboli or air emboli.
• Portal vein thrombosis.
• Dysrhythmias.
• Volume overload.
• Cardiorespiratory arrest or failure.

2. Fluid and Electrolyte Disturbances:

• Hyperkalemia.
• Hypernatremia.
• Hypocalcemia.
• Hypoglycemia.
• Acidosis.

3. Hematological:
• Thrombocytopenia.
• Disseminated Intravascular Coagulation (DIC).
• Transfusion reactions.

4. Infection: see I.5.

5. Mechanical:
• Injury to donor cells (especially from overheating).
• Injury to vessels.
• Blood loss.

- 100 -
Blood to be used in exchange transfusion:
• In Rh hemolytic disease:
o If blood is prepared before delivery, it should be Type O Rh
negative crossmatched against the mother.
o If blood is prepared after delivery, it should be the same ABO
group of the infant or Type O Rh negative. Blood is
crossmatched against the mother and the infant.
• In ABO incompatibility:
o Blood should be Type O of the same Rh group of the infant,
crossmatched against the mother and the infant. Usually Type O
cells are used with AB plasma to ensure that no anti-A or anti-B
antibodies are present.

Part II: 4.

- 101 -
II.4.1.4. Specific Clinical Situations
• The majority of transfusions are given to pre-term infants who are
very unwell:
o To replace blood samples taken for laboratory testing.
o To treat hypotension and hypovolemia.
o To treat the combined effect of anemia of prematurity and blood
loss due to sampling.
A neonate who requires one blood transfusion will often need to be
transfused again within a period of days, as neonates do not have an
effective EPO response to anemia.

Table 22: Estimated Pediatric Blood Volumes

Premature Infants 100 ml/kg
Term Neonate 85-90 ml/kg
Older than 1 Month 80 ml/kg
Older than 1 Year 70 ml/kg

• Critically ill neonates:

o Record the volume of each blood sample taken. If 10% of the
blood volume is removed over 24-48 hours, it should be replaced
with PRCs.
o Critically ill neonates may need to have their Hb level maintained
in the range of 13-14 g/dl to ensure adequate tissue perfusion.
• Convalescent very low birth weight babies:
o Measure the Hb at weekly intervals. The Hb level will drop 1 g/dl
per week on average.
o Do not transfuse on the basis of the Hb level alone. Although Hb
levels of 7 g/dl or less require investigation, transfusion may not
be required.

- 102 -
Table 23: IV Fluids Used in Neonatal and Pediatric Intensive Care
Units

IV Fluid Sodium Potassium Others

Normal Saline 150 mEq/l - -

(0.9%)
3% Saline 513 mEq/l - -

Kadalex
(KCl 0.2% & - 27 mEq/l -
Dextrose 5%)
Strong KCl (15%) - 2 mEq/ml

Ringer’s Solution 147.5 mEq/l 4 mEq/l Ca: 4 mEq/l

Ringer’s Lactate 130 mEq/l 4 mEq/l

Ca: 2.7 mEq/l
Solution HCO3 : 28 mEq/l

0.45 NaCl with 5% 77 mEq/l - -

Dextrose
0.18 NaCl with 5% 30 mEq/l - -
Dextrose
Neoment Solution 30 mEq/l 10 mEq/l Glucose: 120 g/l

Glucose: 100 g/l

Pediment Solution 37 mEq/l 20 mEq/l
Calcium: 4 g/l

NaHCO3 5% 595 mEq /l - -

Part II: 4.

NaHCO3 8.4% 1,000 mEq/l - -

Dextrose 5% - - Glucose: 50 g/l

Dextrose 10% - - Glucose: 100 g/l

Dextrose 25% - - Glucose: 250 g/l

- 103 -
• Neonates with late anemia:
Consider transfusing an infant if anemia is thought to be the cause of:
o Poor weight gain.
o Fatigue while feeding.
o Tachypnea and tachycardia.
o Other signs of decompensation.
• Neonatal Allo-Immune Thrombocytopenia (NAIT):
NAIT is a cause of intrauterine cerebral hemorrhage.
o Transfusion of washed, irradiated compatible platelets should be
used. Mother’s platelets can be used as they lack the causative
Ag. NAIT develops in the same way as HDN.
• Polycythemia and Hyperviscosity:
Partial exchange transfusion is often used for treatment of symptomatic
polycythemia:
o Healthy term infants appear to be at little risk of polycythemia
and hyperviscosity and do not need to be screened routinely.
o In polycythemic neonates with mild or no symptoms, keeping the
baby warm and well hydrated is probably all that is required to
prevent micro-thrombosis in the peripheral circulation.
o The generally accepted screening test is a central venous Hct of
65% or more.
o In infants with suspected hyperviscosity, it is recommended that
Hct values are measured by micro-centrifugation since viscosity
tests are unavailable to most physicians.
o All infants with significant symptoms should undergo partial
exchange with 4.5% albumin to bring the Hct down to a safe
level of 50-55%.

- 104 -
Minimizing the Risks and Increasing the Effective Use of Neonatal
Transfusion:
The following practical measures reduce the risks of neonatal
transfusion and increase its effectiveness:
• For an infant who is likely to need several ‘top-up’ transfusions over a
period of days or weeks, use red cells in additive solution prepared in
pediatric packs from a single unit of blood to decrease donor exposure.
• Reduce blood loss from diagnostic sampling:
o Avoid unnecessary repeat compatibility testing.
o Avoid non-essential laboratory tests.
o Where possible, the laboratory should use micro-methods and should
select suitable small sample tubes.
• Avoid transfusing blood donated by blood relatives as the risk of
GvHD is increased.
• Avoid CMV infection in recipient:
o CMV infection or reactivation may complicate the management of
sick infants. CMV may be transmitted by blood or reactivated
infection by allogenic leucocyte transfusion.
o Use CMV negative donation and/or leucocyte-depleted component.

Part II: 4.

- 105 -
II.4.2 Transfusion in Obstetrics
More than 500,000 women worldwide die every year due to pregnancy
complications. Hemorrhage is the major cause of mortality globally and in
Egypt, according to the last Egyptian Maternal Mortality report in 2001.

Hematological changes during pregnancy:

• An increase of 40-50% in plasma volume occurs, reaching its
maximum by week 32 of gestation. This is accompanied by a
similar increase in cardiac output. The WB volume increases from
60 ml/kg to 75 ml/kg (from 3.6 l to 5.2-6 l).

• The mother’s red cell mass increases 18-25% during pregnancy.

This occurs more slowly than the increase in plasma volume. This
discrepancy between the rate of increase of plasma volume and red
cell mass results in a physiological reduction in Hb concentration
during pregnancy.

• The body can tolerate up to a 25% loss of blood volume. During

pregnancy a blood loss of up to 1.5 l (~25%) is tolerated and the
BP is NORMAL.

Definition of major obstetric hemorrhage:

Major obstetric hemorrhage has been variously defined as either an ante-
partum or post-partum loss of more than 1,000-1,500 ml of blood. Primary
Postpartum Hemorrhage (PPH) is defined as a blood loss greater than 500-
1,000 ml during the first 24 hours after delivery. Approximately 500 ml
(250 mg iron) and up to 1,000 ml of blood are lost during a cesarean
section. This blood loss rarely necessitates transfusion.

- 106 -
Prevention of major obstetric hemorrhage:
A. Identify the patient at risk of hemorrhage.
1. Risk factors identifiable before the onset of labor:
• Proven abruptio placentae.
• Known placenta previa.
• Multiple pregnancy.
• Pre-eclampsia/gestational hypertension.
• Previous PPH.

2. Risk factors apparent during labor/delivery:

• Delivery by emergency cesarean section.
• Retained placenta.
• Operative vaginal delivery prolonged labor
(> 12 hours).
• Big baby (> 4 kg).
• Pyrexia in labor.
• Coagulation defects or patients on anticoagulants:
may intensify all of the above.

B. Management of the third stage of labor.

Manage the third stage of labor actively by prophylactic
oxytocics:
• Syntometrine (Ergometrine 0.5 mg plus Oxytocin 5
IU) or,
• Oxytocin 10 units IV.
Part II: 4.

C. In the rare event of a woman coming to delivery fully

anticoagulated on Warfarin, FFP should be given rapidly to return
the PT to normal (urgent reversal of Warfarin anticoagulation = 5-
8 ml/kg of FFP). On delivery, the infant should be given Vitamin
K and FFP and screened for internal hemorrhage.

- 107 -
D. In the event of a woman coming to delivery while receiving
therapeutic Heparin, the infusion should be stopped. Heparin
activity will fall to safe levels within an hour. Protamine sulphate
will reverse activity more rapidly, if required.

E. Prophylactic platelet transfusion is rarely indicated in surgical

situations with thrombocytopenia due to decreased platelet
production when the platelet count is > 100 x 109/l and is indicated
when platelet count is < 50 x 109/l.

F. Vaginal delivery or small episiotomy procedures ordinarily

associated with insignificant blood loss may be undertaken if the
platelet count is < 50 x 109/l. Management of all cases of ante-
partum hemorrhage should be in a hospital facility with a blood
bank. An ultrasound examination should be performed to
determine the placental site, presence of retroplacental hematoma,
fetal viability and maturity. The fetus should be monitored daily
with a Cardiotocogram (CTG).

G. Deliver at 37-38 weeks gestation, or earlier if the bleeding

endangers the mother or the fetus. Give anti-D Ig for Rh negative
women who are bleeding.

- 108 -
Treatment of obstetric hemorrhage:
A. Management of estimated blood loss 500-1,000 ml, with no
clinical shock:
If resuscitation is necessary, perform the following:
• Venepuncture for: IV access with 14 G cannula.
• Draw 20 ml of blood.
• Crossmatch 2 units.
• Perform a full blood count.
• Perform a clotting screen.
• Perform bedside clotting test: Use 5 cc of blood in a
test tube with no anticoagulant. Clot must form
within 6 minutes and should not be dissolved before
30 minutes. If lyses occur earlier, DIC is suggested.
• Commence crystalloid solution (e.g. Hartmann’s
infusion).
• Perform clinical monitoring (record the pulse and BP
frequently).

Part II: 4.

- 109 -
 B. Management of estimated blood loss > 1,000 ml or any clinical
signs of shock:
Simultaneously: communicate, resuscitate, monitor/investigate, and stop
the bleeding:

1. Communicate:
Alert all key staff for emergency care: OB specialist, nurses, blood
bank, anesthesiologist and hematologist.
2. Resuscitate: (Refer to Table 14)
• IV access with 14 G cannula.
• Tilt the head in a downward position.
• Give Oxygen by mask, 8 l/min.
• Crystalloids and colloids are given to increase the
intravascular volume:
i. Crystalloid (e.g. Ringer’s) maximum 2 l.
ii. Colloid (e.g. Gelofusine, Hemocel, human albumin 4.5%)
maximum 1.5 l.
• Blood transfusion is only given to increase Oxygen carrying
capacity:
i. Transfuse crossmatched blood as soon as possible, if
blood loss is estimated to be more than 1,500 ml. Until
the blood arrives, infuse as rapidly as required. If no
crossmatched blood is available, give O negative blood.
• Use a warming device.
• Use a compression cuff pump.
• Do not use a blood filter.
• Do not give dextrans.
• Give up to 1 l of FFP and 10 units of cryoprecipitate if
clinically indicated.

- 110 -
3. Monitor/Investigate:
• Crossmatch 6 units.
• Perform a full blood count.
• Perform a clotting screen.
• Continuously monitor the temperature, pulse and BP.
• Use a pulse oximeter.
• Insert a Foley’s catheter: calculate hourly urine output.
• Monitor CVP in cases of massive hemorrhage.
• Discuss transfer to ICU.
• Perform clinical monitoring.
4. Stop the Bleeding:
• The most common cause of PPH is uterine atony. However,
clinical examination must be undertaken to exclude other
causes:
i. Retained products (placenta, membranes, clots).
ii. Vaginal/cervical lacerations or hematoma.
iii. Ruptured uterus.
iv. Broad ligament hematoma.
v. Extra-genital bleeding.

• When uterine atony is perceived to be the cause of the PPH, the

following measures should be instituted, in turn, until the
bleeding stops:
i. "Rub up the fundus" to stimulate contractions.
ii. Ensure bladder is empty (Foley catheter, leave in situ).
Part II: 4.

iii. Give Syntocinon 10 units by slow IV injection.

iv. Give Ergometrine 0.5 mg by slow IV injection.
v. Perform a Syntocinon infusion (30 units in 500 ml of
Hartmann’s at 125 ml/hr).
vi. Administer Misoprostol rectal suppositories 400-800 µg.

- 111 -
• If conservative measures fail to control the hemorrhage, initiate
surgical hemostasis (laparotomy) by:
i. Bilateral ligation of uterine arteries.
ii. B-Lynch procedure.
iii. Bilateral ligation of internal iliac (hypogastric arteries).
iv. Hysterectomy. Resort to hysterectomy sooner rather than
later (especially in cases of placenta accreta or uterine
rupture).

- 112 -
II.4.3. Transfusion in GIT and Hepatic Disease

Gastrointestinal bleeding:
Gastrointestinal bleeding is not uncommon and has a significant
mortality risk.

Causes of gastrointestinal bleeding:

• Upper GIT bleeding (peptic, gastric, duodenal ulcers).
• Esophageal varices (usually due to chronic liver disease) can present
as anemia due to chronic bleeding, hematemesis or melena.
• Lower GIT bleeding presents as anemia with a positive fecal occult
blood test or fresh blood in or on the feces.

Management:
• Resuscitate the patient (see II.2.).
• Find the source of bleeding (by endoscopy if possible).
• Offer specific management according to the cause of bleeding.

Specific considerations in hepatic patients:

• Even with small hemorrhage, admission to the nearest hospital with a
blood transfusion facility is advisable due to the high possibility of
recurrence.
• Beta blockers (e.g. Propranolol), usually used in patients with portal
hypertension as prophylaxis against bleeding may mask the
Part II: 4.

compensatory tachycardia.
• Liver patients may have associated coagulopathy and/or
thrombocytopenia, which should be corrected to control the bleeding.
• Over-transfusion should be avoided as it may exacerbate the portal
hypertension and cause further bleeding.
• An Hct of 30% should never be exceeded.

- 113 -
 • Saline infusions should be avoided as they aggravate ascites and salt
and water retention.

Coagulopathy in hepatic patients:

• Management is directed at prevention or correction of Vitamin K
deficiency by administration of parenteral or oral Vitamin K (0.2
mg/kg/day).
• If PT is more than 3 seconds (prolonged INR > 1.2) after IV Vitamin
K for three days, give FFP (effective only for a few hours) before any
surgical procedure (e.g. liver biopsy, etc.).
• It is not necessary to correct PT by FFP except if there is active
bleeding, in the case of surgical interventions, or while awaiting liver
transplantation.
• In cirrhosis, F VII is the first factor to be depleted and because of its
short half-life, replacement with plasma often fails to correct PT.
Selective replacement with F VII can correct PT in such cases.
• DDAVP may cause transient improvement in PTT and BT with an
increase in F VIII and vWF in cirrhotic patients with persistent
severe coagulopathy in spite of FFP administration.
• Dysfibrinogenemia (manifested as prolonged PTT) in the presence of
a normal fibrinogen level and FDPs may contribute to coagulopathy
in liver disease.

- 114 -
II.4.4. Transfusion in Renal Diseases

Anemia of chronic renal failure:

Anemia is an inevitable and often severe complication of chronic renal
failure. It results from a variety of factors including:
• Defective EPO production:
• This is because in uremic patients, the normal response to
hypoxemia, by increasing the secretion of EPO, is blunted.
• Reduced erythrocyte survival: due to accumulation of toxic products.
• Dialysis-associated blood losses.
• Spontaneous bleeding due to defective platelet plug formation.
• Hypersplenism may rarely be associated with chronic dialysis and
leads to the sequestration of erythrocytes and the destruction of
circulating red cells.

A. Blood Transfusion in Chronic Renal Failure:

Packed Red Cells (PRCs):
In many cases, the only effective therapy in patients with chronic failure
is red cell transfusion which should be prescribed cautiously because
repeated red cell transfusions (apart from their well-known complications)
produce more undesirable effects in these patients.
In patients with uremia, an inverse relation has been observed between
the Hct and the bleeding time. Red cell transfusion has been reported to
decrease the bleeding tendency. The mechanism is not known but red cells
Part II: 4.

seem to play a role in facilitating the adherence of platelets to the

subendothelium.
Hyperkalemia is expected to be a particular risk to uremic patients.
Therefore it is recommended that reasonably fresh blood (up to 7 days old)
be selected for such patients.

- 115 -
 Platelets:
Uremic patients have a prolonged BT and are at risk of abnormal
bleeding due to accumulation of some toxic substances in the plasma that
can inhibit platelet function.
Platelet transfusions are of limited value in uremic patients because the
transfused platelets will acquire the same functional impairment.
Dialysis improves platelet function and in this respect peritoneal dialysis
appears to be more effective than hemodialysis. This seems to be due to
more efficient loss of the lower molecular weight substances that damage
platelet function.

B. Desmopressin Acetate (DDAVP):

Desmopressin is a synthetic analogue of L-arginine vasopressin, the
naturally occurring Anti-Diuretic Hormone (ADH). DDAVP has been
shown to produce a transient correction of the BT in uremic patients.
Although DDAVP is known to induce a transient increase in vWF and F
VIII, the mechanism by which it shortens the BT in uremia is still unclear.

Because infusion of DDAVP presents no infectious risk as with blood component

transfusion, it should be considered a first-line treatment option for the control of
acute uremic bleeding or prophylaxis of uremic bleeding prior to invasive procedures.

C. r-HuEPO in Renal Failure:

The best treatment of anemic patients is the use of recombinant Human
Erythropoietin (r-HuEPO). The response to treatment is impressive and the
need for transfusion is markedly decreased.

Transfusions should be avoided as much as possible, not only because of the well
known infectious risks and the fluid overload in cardiac patients, but also to avoid
inhibition of normal EPO secretion exerted by chronic hypoxemia.

- 116 -
II.4.5. Transfusion in Transplant Patients
• All cellular blood components received during or after organ
transplantation should be irradiated (to prevent occurrence of GvHD
in such patients under immunosuppression).
• Only leucocyte-depleted blood, PRCs and platelet concentrates
should be used in order to decrease the possibility of CMV and/or
EBV infection, FNHTR, etc.
• The use of cell savers intra-operatively (specially in liver
transplantation where bleeding may be a problem) is very helpful.
Blood is aspirated from the abdominal cavity, washed repeatedly, re-
suspended then re-infused.
• During liver transplantation and in the post-operative period, the Hb
should not exceed 10 g/dl. This is one of the ways to prevent hepatic
artery thrombosis, a serious complication.
• Constant intra-operative monitoring by thrombo-elastograghy allows
the anesthetist to determine the cause of coagulopathy (hyper-
fibrinolysis, coagulation factor deficiency, or platelet deficiency) and
to manage it accordingly.
• The principles of post-operative fluid management are to maintain
circulating blood volume by providing 2/3 maintenance fluid with
crystalloid while replacing wound drains 1 ml to 1 ml by FFP until
the coagulation profile has improved, then replacing half by 4.5%
albumin to keep the urine output > 1 ml/kg/hr and CVP > 5-6 mm
Part II: 4.

Hg.

- 117 -
II.4.6. Transfusion in Hematological Diseases

II.4.6.1. Bone Marrow Failure

Failure of the bone marrow is defined as the inability to produce
adequate cells to maintain normal counts in the peripheral blood. It usually
presents as pancytopenia in the peripheral blood.

Management:
• Treat the primary cause.
• Maintain fluid balance.
• Give supportive treatment as nutrition, toxin control, etc.
• Stop potentially toxic drug treatments.
• Provide transfusion support with RBCs and platelets for severe
anemia and thrombocytopenia, respectively.

Hazards and precautions of blood transfusion:

• Graft versus host disease (GvHD).
• Cytomegalovirus infection (CMV).

II.4.6.2 Hereditary Hematological Disorders

A. Beta Thalassemia Major:

Management:
1. Transfusion:
• Planned blood transfusions can save and improve the quality
of lives by helping to avoid complications of hypertrophied
marrow and early cardiac failure.

- 118 -
 • The aim is to transfuse red cells in sufficient quantity and
frequency to suppress erythropoiesis. An Hb level between 8-
10 gm/dl is adequate.
Leucocyte-depleted PRCs are used to avoid transfusion reactions
occurring in repeatedly transfused patients. Pre-storage leucocyte depletion
is preferred.
The patient’s ABO, Rhesus, Kell, Kidd and Duffy systems should be
typed at diagnosis and before beginning the transfusion, thereby giving
compatible blood and avoiding development of red cell antibodies.
• Pre-transfusion and follow-up management:
o A regular transfusion regimen is indicated if Hb level <7
g/dl.
o Serum ferritin, liver functions, hepatitis markers, blood
glucose and cardiac functions should be monitored.
o Vaccinations:
Administer the vaccine before the transfusion or as
scheduled and include:
• Hepatitis A.
• Hepatitis B.
And upon deciding to perform a splenectomy, add the
following:
• Pneumoccocal vaccine.
• Meningococcal vaccine.
• Hemophilus influenza vaccine.
Part II: 4.

• Growth and puberty charts should reflect the proper

transfusion and chelation regimen.

- 119 -
2. Splenectomy (not before 6 years of age):
• Splenomegaly increases anemia by the pooling and destruction
of blood. Splenectomy may be required and will usually
reduce the transfusion requirement.
3. Chelation Therapy:
• Desferrioxamine (Desferral) is administered SC using a
special pump in a dose of 25-40 mg/kg/day to a maximum of
50 mg/kg/day, 5 days a week. The dose is given over 8-10
hours.
• Deferiprone is a new orally active drug capable of chelating
iron when given alone or in combination with
Desferrioxamine. The pediatric and adult dose ranges from 50-
100 mg/kg/day.
4. Vitamin C:
• Given as 200 mg orally to promote iron excretion on the day
of chelation only.
5. Vitamin D and Calcium:
• Given for parathyroid failure.
6. Folic Acid:
• Especially in non-transfused patients like B Thalassemia
intermedia, a dose of 5 mg/day is given orally.
7. Long-term Penicillin:
• Only if splenectomy is decided. It is given in addition to
vaccination.
8. Endocrine Replacement:
• If diabetes and pituitary failure develop.

- 120 -
 9. Bone Marrow Transplantation:
• Is an option for curative treatment in B Thalassemics who are
well chelated, without liver damage and when a HLA donor is
available.

B. Sickle-cell Disease:
Most patients with sickle-cell disease are transfusion independent. A
partial exchange transfusion is needed in some cases to reduce the
circulating Hb S to less than 50%.

Indications of transfusion in sickle-cell anemia:

• Prevention of crisis and long-term disability:
Transfusion is not indicated to raise a low Hb level. Patients
are well adapted to Hb levels of 7 g/dl. The aim of transfusion
is to maintain a sufficient proportion of normal Hb A (30% or
more) in the circulation to minimize the risk of sickling
episodes. This can be done by regular transfusions.
• Treatment of crisis and severe anemia:
Prompt transfusion in a sequestration crisis and aplastic crisis
can be life saving.
• Sequestration crisis:
There is a sudden pooling of blood in the spleen which
becomes temporarily greatly enlarged. This leads to
circulatory shock. The circulating blood volume must be
urgently restored by IV fluid. Blood transfusion is usually
Part II: 4.

needed.
• Aplastic crisis:
Usually triggered by Parvovirus infection. There is transient
acute bone marrow failure and transfusion may be needed
until the marrow recovers with or without IV Ig.

- 121 -
• Vaso-occlusive crisis:
Leading to pain and infarction, Prophylactic use of
hydroxyurea with or without EPO reduces vaso-occlusive
crisis. Ensure treatment of infections, because infections
(especially pulmonary) aggravate hypoxia and precipitate
vaso-occlusive crisis.
• Pregnancy:
Routine transfusion during pregnancy is considered in patients
with a bad obstetric history or frequent crises.
• Preparation for surgery:
Preparation for delivery or surgery with anesthesia may
include transfusion to bring the proportion of Hb S below
30%. Anesthetic techniques and supportive care should ensure
that blood loss, hypoxia, dehydration and acidosis are
minimized.

- 122 -
C. G6PD Deficiency:
• G6PD deficiency is commonly asymptomatic and can cause
jaundice and anemia precipitated by fava beans, infections,
drugs or chemicals.
• Hemolysis will stop once the cells that are most deficient in
G6PD have been destroyed.
• It is important to remove or treat any other identifiable cause
for hemolysis.
• Transfusion is not required in most cases of G6PD deficiency.
Transfusion may be life saving in severe hemolysis when the
Hb continues to fall rapidly.
• Exchange transfusions are indicated for neonates at risk of
kernicterus and who are unresponsive to phototherapy.

D. Autoimmune Hemolytic Anemia:

• Communication between the clinician and the blood bank
physician is essential for patient care, because the serologic
evaluation and selection of appropriate blood is time-
consuming.
• The decision to transfuse should consider the severity of the
anemia, the risk of not performing the transfusion and the
potential benefit of alternative therapy.
• Although transfused red cells may not have normal survival in
patients with red cell antibodies, blood transfusion may
provide temporary benefit. The presence of autoantibodies
Part II: 4.

may mask the presence of co-existing alloantibodies thus

increasing the risk of ‘alloantibodies-induced hemolytic
transfusion reaction’. Also, the autoantibodies themselves
may cause decreased survival of transfused red cells. Thus the
minimum volume of red cells that provides clinical benefit
should be transfused slowly.

- 123 -
• Leucocyte-depleted blood components should be used to
minimize the risk of FNHTRs and to decrease the risk of
alloimmunization to HLA and platelet antigens, and to reduce
the risk of CMV transmission.
• In case of cold antibodies, using an in-line blood warmer and
warming the patient may be of value.
• Procedures requiring systemic hypothermia such as
cardiopulmonary bypass may lead to complement activation
and hemolysis.
• If plasmapheresis is used, warming of the extra-corporeal
circuit may be beneficial.
• Steroids could be used to cover an unavoidable blood
transfusion in cases of incompatibility.

- 124 -
II.4.7. Transfusion in Surgical Patients

General ways to reduce amount of blood transfused in a surgical patient:

• Reduce blood loss.
• Maximize RBC production.
• Maximize Oxygen delivery.
• Lower threshold level when to transfuse (tolerate lower Hb values).

N.B.: These recommendations assume elective surgery and might not be

appropriate for a patient requiring urgent or emergency surgery.

Pre-operative:
1. Take a complete history, including tendency to bleed and a
description of any previous surgeries.
2. Perform laboratory screening tests, including a complete blood cell
count and coagulation screening tests. If blood loss is expected,
submit a specimen to the blood bank (Type and Hold, Type and
Screen or Type and Crossmatch).
3. Consider autologous blood collection.
4. Consider EPO to increase red blood cell production.
5. Manage pre-operative anemia with iron and folate, and treat
Vitamin B12 deficiency.
6. Stop Aspirin or other drugs with antiplatelet activity sufficient to
remove the effect by the time of surgery (7 days for Aspirin).
Part II: 4.

7. Weigh the patient and estimate the blood volume.

8. If the patient is receiving anticoagulants, develop a plan to reverse
the anticoagulant effect of the drug prior to surgery.

- 125 -
Peri-operative:
1. Consider acute normovolemic hemodilution.
2. If available and the surgery is appropriate, consider intra-operative
RBC salvage.
3. Consider hypotensive surgery, if appropriate.
4. Warm all fluids to avoid hypothermia.
5. During surgery maintain meticulous hemostatis. Consider use of
fibrin glues and sealants.
6. Use of pharmacological agents (tranexamic acid, DDAVP,
aprotonin).

Post-operative:
1. Accept a lower post-operative Hb concentration before transfusing.
2. If transfusion is necessary, limit the number of units transfused
(preferably 1) unless the patient is hemorrhaging.
3. Use supplemental Oxygen.
4. Prescribe iron, folate and Vitamin B12.

- 126 -
Annexes
 Annex 1

PRESCRIBING BLOOD: A CHECKLIST FOR CLINICIANS

Prescription decisions should be based on national guidelines on the ACUB, taking individual
patients’ needs into account.
Before prescribing blood or blood products for a patient, ask yourself the following questions:

1. What improvement in the patient’s clinical condition am I aiming to achieve?

2. Can I minimize blood loss to reduce this patient’s need for transfusion?

3. Are there any other treatments I should give before making the decision to transfuse, such as
IV replacement fluids or Oxygen?

4. What are the specific clinical or laboratory indications for transfusion for this patient?

5. What are the risks of transmitting HIV, hepatitis, syphilis or other infectious agents through
the blood products that are available for this patient?

6. Do the benefits of transfusion outweigh the risks for this particular patient?

7. What other options are there if no blood is available in time?

8. Will a trained person monitor this patient and respond immediately if any acute transfusion
reactions occur?

9. Have I recorded my decision and reasons for transfusion on the patient’s chart and the blood
request form?

Finally, if in doubt, ask yourself the following question:

10. If this blood were for my child, or myself, would I accept the transfusion in these
circumstances?
 Annex 2 A Sample Blood Request Form

 ‫  ام و‬
‫ا  ا‬

‫أ‬ ‫ذآ‬ ‫اع‬ ‫ر اد‬
‫ر ال‬ ‫ر ال‬ ‫ا‬
Diagnosis
Reason for transfusion
Previous transfusion Yes□ No□
Previous transfusion reactions Yes (Date) No□
Previous pregnancy Yes □ No□
Any relevant medical history Blood pressure Kidney status
Hb level
………………………………………………………………………………
COMPONENTS REQUESTED
Packed red cells Units
Platelet concentrate Units □Ab screening
Random donor pl. Units □Phenotyped
Single donor plt. Units □Leucodepleted (filtered)
Fresh frozen plasma Units
Cryoprecipitate Units
Cryodepleted plasma Units
Frozen plasma Units

Routine : needed on Date Time

Emergency
Physician signature
Date
………………………………………………………………………………
For blood bank‫! ها اء   ام‬
Patient Name
Patient blood group ABO / Rh
Issued blood units
Serial Barcode Blood component Tube Crossmatching Expiry
No group line No result date

Test done by Date

Author: Dr. Mervat Doss

F/NBTS/AUB/003/01 Implementation date: 01/12/05
 Annex 3 A Sample Blood Ordering Schedule

Blood ordering schedule: a guide to expected normal blood usage for

surgical procedures in adult patients

Procedure Action Procedure Action

General Surgery Vascular
Cholecystectomy G&S Aorto-iliac endarterectomy X-M 4
Exploratory Laparotomy G&S Femoral endarterectomy G&S
Liver Biopsy G&S Femoro-popliteal bypass G&S
Hiatus Hernia X-M 2 Ilio-femoral bypass X-M 2
Partial Gastrectomy Resection abdominal aortic X-M 6
G&S
aneurysm
Colectomy X-M 2
Simple Mastectomy G&S Urology
Radical Mastectomy X-M 2 Ureterolithotomy G&S
Thyroidectomy X-M 2 (+ 2) Cystectomy X-M 4
Open nephrolithotomy X-M 2
Cardiothorathic Open prostatectomy X-M 2
Angioplasty G&S Renal transplantation X-M 2
Open Heart Surgery X-M 4 (+ 4)
Bronchoscopy G&S Neurosurgery
Open Lung/Pleural Biopsy G&S Head Injury G&S
Lobectomy X-M 2 Vascular Surgery (e.g. aneurysms) X-M 3
Pneumonectomy X-M 2 Meningioma X-M 4

X-M = Crossmatch G&S = ABO/Rh group and antibody screen

(+ ) indicates additional units may be required, depending on surgical complications
 Annex 3 A Sample Blood Ordering Schedule
(Continued)
Blood ordering schedule: a guide to expected normal blood usage for
surgical procedures in adult patients

Procedure Action Procedure Action

Orthopedics Obstetrics and gynecology
Disc surgery G&S Dilatation and curettage G&S
Laminectomy G&S Normal delivery G&S
Total hip replacement X-M 2 (+ 2) Cesarean section G&S
Nail for fracture neck of G&S Placenta previa X-M 4
femur
Internal fixation of femur X-M 2 Antepartum/postpartum X-M 2
hemorrhage
Simple Hysterectomy G&S
Internal fixation of tibia or G&S Radical Hysterectomy X-M 2
ankle
Total hip arthroplasty X-M 3 Myomectomy X-M 2
Spinal decompression X-M 2 Radical Oophorectomy X-M 4
Hydatiform mole X-M 2

X-M = Crossmatch G&S = ABO/Rh group and antibody screen

(+ ) indicates additional units may be required, depending on surgical complications