Practical Transfusion Medicine E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 1364

Veröffentlichungsjahr: 2017

Beschreibung

The fifth edition of this practical textbook on transfusion medicine has been thoroughly revised with the latest in scientific and technological developments and edited by a leading team of international expert haematologists, including new co-editor Mark H. Yazer MD.

• A succinct and user-friendly resource of transfusion medicine for clinicians, scientists and trainees with key points, charts and algorithms
• Discusses practice in blood centres and hospitals including regulatory aspects, transfusion safety, production and storage, donor care, and blood transfusion in a global context
• Coverage of cellular and tissue therapies and organ transplantation including stem cell collection and haematopoietic stem cell processing and storage
• Review of the development of the evidence-base for transfusion medicine
• Content on the clinical practice for transfusion and alternatives to transfusion

Leseprobe

Table of Contents

Cover

Title Page

List of Contributors

Preface

1 Introduction

Blood Donation Worldwide

Changing Landscape of Transfusion Risks

Immunohaematology

Clinical Use of Blood Components: Evolution Based on Evidence

Urgent Transfusion

Patients Requiring Chronic Transfusion Support

Obstetric, Neonatal and Paediatric Transfusion Medicine

Haemostasis and Transfusion

Cellular Therapies, Transplantation, Apheresis

The Future

Conclusion

References

Part I: Basic Principles of Immunohaematology

2 Essential Immunology for Transfusion Medicine

Cellular Basis of the Immune Response

B‐Cell Activation and T‐Cell‐Dependent Antibody Formation

Humoral Immune Response

Antibody Effector Functions

Red Blood Cell Antibodies Illustrating the Above Principles

Antibody and Complement‐Mediated Blood Cell Destruction

Clinical Aspects Related to Alloimmunisation Against Blood Cell Antigens

References

Further Reading

3 Human Blood Group Systems

Introduction

The ABO System

The Rh System

Other Blood Group Systems

Biological Significance of Blood Group Antigens

References

Further Reading

4 Human Leucocyte Antigens

Introduction

HLA Class I Genes

HLA Class II Genes

Genetic Organisation and Expression of HLA Class II Genes

Expression of HLA Molecules

Genetics

Function of HLA Molecules

Identification of HLA Gene Polymorphism

Formation of HLA Antibodies

Detection of HLA Antibodies

Clinical Relevance of HLA Antigens and Antibodies

HLA and Disease

References

Further Reading

5 Platelet and Neutrophil Antigens

Antigens on Platelets and Granulocytes

Human Platelet Antigens

Human Neutrophil Antigens

References

Further Reading

6 Pretransfusion Testing and the Selection of Red Cell Products for Transfusion

Introduction

Determining the Recipient’s ABO Group and Screening for Unexpected Antibodies

Crossmatching Techniques

Selection of Red Cells for Transfusion

Selection of Platelets and Plasma Components

References

Further Reading

Part II: Complications of Transfusions

7 Investigation of Acute Transfusion Reactions

Introduction

Understanding the Clinical Presentation and Differential Diagnosis

General Approach for Investigation and Treatment of Acute Transfusion Reactions

Algorithm

References

Further Reading

8 Haemolytic Transfusion Reactions

Definition of a Haemolytic Transfusion Reaction

Pathophysiology of HTRs

Acute HTRs

Delayed HTRs

Acute Haemolysis from ABO‐Incompatible Platelet Transfusions

References

Further Reading

9 Febrile and Allergic Transfusion Reactions

Introduction

Febrile Non‐haemolytic Transfusion Reactions

Allergic Transfusion Reactions

References

10 Lung Injury and Pulmonary Oedema After Transfusion

Definition

Incidence, Outcomes and Recipient Risk Factors

Clinical Manifestations

Differential Diagnosis

Pathogenesis

Lung Histology

Types of Blood Components That Can Cause TRALI

Mitigation Strategies

Patient Management

References

Further Reading

11 Purported Adverse Effects of ‘Old Blood’

Introduction

In Vitro Changes During Red Cell Storage

Studies on Clinical Effects of ‘Old’ Red Cells

Conclusion

References

Further Reading

12 Transfusion‐Induced Immunomodulation

Introduction

Mitigation of Immunomodulation After Red Cell Transfusion

Leucocyte‐Reduced Allogeneic Red Cell Transfusions Reduce Mortality In Cardiac Surgery

Observational and Cohort Studies of Transfusion Immunomodulation Link Red Cell Transfusions to Both Beneficial and Adverse Outcomes

Duration of Red Cell Storage and Immunomodulation

Experimental Studies and Transfusion Immunomodulation

Conclusion

References

Further Reading

13 Transfusion‐Associated Graft‐Versus‐Host Disease and Microchimerism

Transfusion‐Associated Graft‐Versus‐Host Disease

Transfusion‐Associated Microchimerism

References

Further Reading

14 Posttransfusion Purpura

Introduction

Definition

Incidence

Clinical Features

Differential Diagnosis

Laboratory Investigations

Pathophysiology

Management

Prevention of Recurrence of PTP

References

Further Reading

15 Transfusion‐Transmitted Infections

Introduction

Transmission of Infections by Blood Transfusion

Transfusion‐Transmitted Infections: Detection and Management

Interventions to Minimise the Impact of Transfusion‐Transmitted Infection

Transfusion‐Transmitted Infectious Agents

References

Further Reading

16 Bacterial Contamination

Incidence of Bacterial Contamination

Blood Components Implicated in Adverse Transfusion Reactions

Contaminant Bacterial Species

Sources of Contamination

Investigation of Transfusion Reactions

Prevention Strategies

References

Further Reading

17 Emerging Infections and Transfusion Safety

Introduction

Emerging Infections

Approaches to the Management of Transfusion‐Transmissible Emerging Infections

Assessing the Risk and Threat of Transfusion Transmissibility

Recognition of Transfusion Transmission of Emerging Infections

Interventions

References

Further Reading

Part III: Practice in Blood Centres and Hospitals

18 Regulatory Aspects of Blood Transfusion

Introduction

The Components of Blood Regulation

The Regulatory Bodies (Table 18.1)

The Role of Blood Transfusion Agencies and Health Professionals Vis‐À‐Vis Regulatory Agencies

References

Further Reading

19 The Role of Haemovigilance in Transfusion Safety

Introduction

Origin and Structures

Definitions and Terminology in Haemovigilance Systems

Adverse Event Detection and Reporting

Haemovigilance System Limitations

Breadth of the System

Analysis of Incident Reports

Reporting Requirements Structure

Data Management

Learning from Experience

Future Directions

Intangible Benefits

References

Further Reading

20 Donors and Blood Collection

Blood Donors: Paid, Directed, Payback and Altruistic

Risks to the Blood Donor

Iron Deficiency in Blood Donors

Blood Collection/Donation Process

Obligations to Donors

References

Further Reading

21 Blood Donation Testing and the Safety of the Blood Supply

Introduction

Red Cell Serological Testing

Microbiological Testing of Blood Donations and Donor Follow‐Up

Quality Framework and Operational Issues

References

Further Reading

22 Production and Storage of Blood Components

Whole Blood and Its Processing to Components

Collection of Components by Apheresis

Regulations, Specifications and Quality Monitoring

Red Blood Cell Production and Storage (Table 22.1)

Platelet Production and Storage (Table 22.2)

Plasma Production and Storage (Table 22.3)

Cryoprecipitate Production and Storage (see Table 22.3)

Granulocyte Production and Storage

Component Modifications

References

Further Reading

23 Blood Transfusion in Hospitals

Introduction

Key Features of Hospital Transfusion Governance

Hospital Transfusion Committees

Working Together to Improve the Transfusion Process

Informed consent

Administration of Blood and Blood Components and Management of the Transfused Patient

Technologies to Reduce Patient Misidentification Errors in Administering Blood

Influencing Clinical Practice

Guidelines, Algorithms and Protocols

Clinical Audit

Surveys

National Schemes

Public and Political Perceptions and Fear of Litigation

Local Investigation and Feedback Following ‘Near Misses’ and Serious Adverse Events

Education and Continuing Professional Development

Centralisation of Transfusion Services

Maximum Surgical Blood Ordering Schedule (MSBOS)

References

Further Reading

24 Blood Transfusion in a Global Context

Introduction

Blood Donors

Use of Blood Products

Systems

Focus on Sub‐Saharan Africa

Improvements

Conclusion: The Future of Blood Transfusion in a Global Context

References

Further Reading

Part IV: Clinical Transfusion Practice

25 Inherited and Acquired Coagulation Disorders

Normal Haemostasis

Investigation of Abnormal Haemostasis

Inherited Haemostatic Defects

Acquired Haemostatic Defects

References

Further Reading

26 Massive Blood Loss

Definition and Burden of Massive Blood Loss

Haemorrhage‐Related Mortality Following Injury

Coagulopathy after Injury

The Limits of Resuscitation with Conventional Blood Products

Efficacy of Damage Control Resuscitation

Can the Lessons of Damage Control Resuscitation for Trauma be Extended to Other Massive Haemorrhage Situations?

Massive Transfusion in Small Children

Conclusion

References

Further Reading

27 Blood Management in Acute Haemorrhage and Critical Care

Introduction

Red Cell Transfusion

Treatment Adjuncts That Reduce Transfusion (see also Chapter 34)

Coagulopathy

Massive Blood Transfusion

Conclusion

References

Further Reading

28 Point‐of‐Care Testing in Transfusion Medicine

Introduction

Limitations of Conventional Coagulation Testing

Point‐of‐Care Testing Options

Point‐of‐Care Testing in Transfusion Algorithms

References

Further Reading

29 Haematological Disease

Introduction

Red Cell Transfusions

Platelet Transfusions

Granulocyte Transfusions

Approach to Complications Associated with Blood Transfusion in Haematology Patients

Iron Overload

References

Further Reading

30 Blood Transfusion in the Management of Patients with Haemoglobinopathies

Introduction

α‐Thalassaemia syndromes

β‐Thalassaemia Syndromes

Sickle Cell Disease

Complications of Transfusions in Haemoglobinopathies

Iron Chelation

Acknowledgement

References

Further Reading

31 Heparin‐Induced Thrombocytopenia

Introduction

Pathogenesis

Epidemiology

Heparin‐Induced Thrombocytopenia: A ‘Clinicopathological’ Syndrome

Laboratory Testing

Treatment

References

Further Reading

32 Immunodeficiency and Immunoglobulin Therapy

Introduction

Primary Immunodeficiency Disorders

Immunoglobulin Therapy

References

Further Reading

33 Transfusing Neonates and Infants

Introduction

Red Cell Transfusions for the Anaemia of Prematurity

Platelet Transfusions for the Thrombocytopenia of Prematurity

References

Further Reading

Part V : Patient Blood Management

34 Part VPatient Blood ManagementDevelopment of a Patient Blood Management Programme

Introduction

Step 1: Leverage Computerised Physician Order Entry (CPOE) Systems to Guide Evidence‐Based Transfusions [1]

Step 2: Reduce All Forms of Waste Related to Blood Transfusion Practices

Step 3: Promote Alternative Blood Transfusion Methods and Systems

Step 4: Promote Anaemia Management Strategies

Step 5: Limit Iatrogenic Blood Loss

Step 6: Provide Blood Management Education, Awareness and Auditing for Clinicians

Cost of Blood

References

Further Reading

35 Perioperative Patient Blood Management

Introduction

Anaemia and Major Surgery

Just Give Blood?

Patient Blood Management in Surgical Practice

Intraoperative Management

Major Haemorrhage

Post‐operative Patient Blood Management

Conclusion

References

Further Reading

36 Restrictive Transfusion Practice and How to Implement It

Introduction

Level 1 Evidence Supports Restrictive Red Cell Transfusion Practices

Strategies for Improving Blood Utilisation

Clinical Decision Support

Improving Blood Utilisation: The Stanford Experience

Future Directions

Conclusion

References

Further Reading

37 Using Data to Support Patient Blood Management

Introduction

Transfusion Triggers and Targets

Blood Utilisation Metrics

Sources of Data

Data Extraction, Analysis and Presentation to Improve Practice

Clinical Outcome Data

Risk Adjustment

Crossmatch‐to‐Transfusion Ratio

Preoperative Anaemia Screening and Management

Conclusion

References

Further Reading

Part VI: Cellular and Tissue Therapy and Organ Transplantation

38 Regulation and Accreditation in Cellular Therapy

Introduction

Haematopoietic Stem Cell Transplant Activity

The Structure of SCT Programmes

European Union Directives and Legislation

The Human Tissue (HT) Act 2004

United States Food and Drug Administration

Non‐governmental (Voluntary) Accreditation

Conclusion: How Do HSCT Programmes Respond to the Challenge?

References

Further Reading

39 Stem Cell Collection and Therapeutic Apheresis

Introduction

Cell Separators

Patient Assessment and Treatment Planning

Haematopoietic Progenitor Cell Mobilisation

Peripheral Blood HPC Collection (Leucocytapheresis)

Plasma Exchange

Red Cell Exchange

Extracorporeal Photochemotherapy (Photopheresis)

Complications of Therapeutic Apheresis

References

Further Reading

40 Haemopoietic Stem Cell Processing and Storage

Introduction

Transplant Procedures

Haemopoietic Progenitor Cell Products

Haemopoietic Progenitor Cell Product Assessment and Specialised Procedures

Storage of Haemopoietic Progenitor Cell Products

Cryopreservation

Thawing of Cryopreserved Haemopoietic Progenitor Cells

Quality Assurance

References

Further Reading

41 Haematopoietic Stem Cell Transplantation

Introduction

Principles of Haematopoietic Stem Cell Transplants

Indications for haematopoietic stem cell transplants

Source of Stem Cells

Donor Care and Selection

Collecting Haematopoietic Stem Cells

Complications of Transplantation

Bone Marrow Transplant Outcome

Post‐Bone Marrow Transplant Chimerism and Molecular Monitoring

Cytotoxic T‐Cell Therapy

Regulatory Aspects of Haemopoietic Stem Cell Transplantation

Conclusion

References

Further Reading

42 Cord Blood Transplantation

Introduction

Umbilical Cord Blood Banking

Clinical Outcomes of Umbilical Cord Blood Transplantation

Advantages and Disadvantages of Umbilical Cord Blood

Future Developments

Conclusion

References

Further Reading

43 Recent Advances in Clinical Cellular Immunotherapy

Introduction

Cellular Immunotherapy in Haemopoietic Progenitor Cell Transplantation

Nonspecific T‐Cell Immunotherapy

Tumour‐Specific or Tumour‐Restricted T‐Cell Immunotherapy

Gene‐Modified T‐Cells for Immunotherapy

Tumour‐Restricted Natural Killer Cell Immunotherapy

Passive Cellular Immunotherapy of Infectious Disease

Technical Advances Facilitating Translational Research in Cellular Immunotherapy

References

Further Reading

44 Tissue Banking

Introduction

Regulation

Consent

Donor Selection and Testing

Tissue Procurement

Tissue Processing

Supply and Traceability of Tissues

Clinical Applications

Serious Adverse Events and Reactions

Advances in Tissue Processing and Regenerative Medicine

Conclusion

References

Further Reading

Part VII: Development of the Evidence Base for Transfusion

45 Observational and Interventional Trials in Transfusion Medicine

Introduction

Types of Clinical Studies

Observational Studies

Randomised Controlled Trials

Conclusion

Acknowledgements

References

Further Reading

46 Getting the Most Out of the Evidence for Transfusion Medicine

What is Meant by Evidence‐Based Medicine?

Hierarchies of Clinical Evidence

Appraisal of Primary Research Evidence for Its Validity and Usefulness

Reviews: Narrative and Systematic

Comparative Effectiveness Research

Evidence Base for Transfusion Medicine

Are There Limitations to Evidence‐Based Practice?

Conclusion

References

Further Reading

47 A Primer on Biostatistics

Incidence and Prevalence

Statistics in Diagnostic Testing

Descriptive Statistics

Differentiating Types of Data and Statistical Tests to be Used

Determining Statistical Significance

Trial Hypotheses and Common Pitfalls of Interpretation

Meta‐analyses and Forest Plots

Conclusion

References

Further Reading

48 A Primer on Health Economics

Introduction

How Economists Think about Transfusions

Economic Evaluation in Transfusion Medicine

Conclusion

References

Further Reading

49 Scanning the Future of Transfusion Medicine

Introduction

Blood Donor and Blood Supply Issues

Hospital Transfusion Service and Patient Care Perspectives

Cellular Therapy – A View to the Future

Afterthoughts

References

Index

End User License Agreement

List of Tables

Chapter 02

Table 2.1 Immunoglobulin classes and their functions.

Chapter 03

Table 3.1 Human blood group systems.

Table 3.2 The ABO system.

Table 3.3 The Duffy system: phenotypes and genotypes.

Table 3.4 Nucleotide polymorphisms in the promoter region and in exon 2 of the three common alleles of the Duffy gene.

Chapter 04

Table 4.1 Number of recognised HLA antigens/alleles.

Table 4.2 Advantages and disadvantages of DNA‐based techniques.

Chapter 05

Table 5.1 Antigen expression on peripheral blood cells.

Table 5.2 Human platelet antigens.

Table 5.3 Human neutrophil antigens.

Chapter 06

Table 6.1 Expected ABO grouping patterns.

Table 6.2 ABO compatibilities between donor and recipient for red cell and plasma‐containing products.

Table 6.3 Recommendations for selection of blood for patients with red cell alloantibodies.

Table 6.4 Summary of clinical studies on the rate of haemolysis following the transfusion of uncrossmatched red cells. Please see original text for complete reference citations.

Chapter 07

Table 7.1 Summary of the signs/symptoms typically observed with different types of acute transfusion reactions.

Table 7.2 Summary of acute transfusion reactions. Data from Callum et al [3] and Popovsky [4].

Chapter 08

Table 8.1 Cytokines implicated in haemolytic transfusion reactions.

Table 8.2 Antibody specificities associated with haemolytic transfusion reactions.

Table 8.3 Fatal haemolytic transfusion reactions reported to the FDA by implicated antibody, 2010–14.

Table 8.4 Immediate medical management of an acute transfusion reaction.

Table 8.5 Laboratory investigation of suspected acute haemolytic transfusion reaction.

Chapter 10

Table 10.1 Recipient risk factors for transfusion‐related acute lung injury.

Table 10.2 Major risk factors for acute respiratory distress syndrome.

Table 10.3 Conditions to be considered when attempting to differentiate TRALI from TACO.

Chapter 11

Table 11.1 Randomised controlled trials of red cell storage duration.

Chapter 13

Table 13.1 Potential methods for leucocyte inactivation.

Table 13.2 Comparison of irradiation guidelines, including dose and indications.

Table 13.3 Cases of TA‐GVHD reported to SHOT 1996–2014.

Table 13.4 Frequency of transfusion from homozygous donors to potential heterozygous recipients.

Chapter 16

Table 16.1 Prevalence of bacterial contamination in platelet concentrates in selected blood centres [1,8].

Chapter 17

Table 17.1 Selected emerging infections potentially or actually transmissible by blood transfusion.

Chapter 18

Table 18.1 Agencies involved in regulatory processes in blood transfusion.

Chapter 20

Table 20.1 Adverse events or reactions in blood donors.

Table 20.2 Infections risks from blood donors.

Chapter 21

Table 21.1 Screening tests on blood donations in five countries as of 2016.

Chapter 22

Table 22.1 Specifications for red cell components.

Table 22.2 Specifications for platelet components.

Table 22.3 Specifications for frozen plasma components.

Chapter 23

Table 23.1 Activities of the hospital transfusion committee.

Table 23.2 Examples of some errors and other problems in the transfusion process, and their potential outcomes.

Table 23.3 Prescription of blood components.

Table 23.4 Requests for blood and blood components.

Table 23.5 Sampling for pretransfusion compatibility testing.

Table 23.6 Collection and delivery of blood components from transfusion storage facility to clinical area.

Table 23.7 Administration of blood components.

Table 23.8 Monitoring of transfused patients.

Table 23.9 Example of Maximum Surgical Blood Order Schedule (MSBOS, general surgery).

Chapter 25

Table 25.1 Laboratory haemostasis screening tests.

Table 25.2 TEG parameters, selected abnormalities and treatment.

Table 25.3 Clinical manifestations and treatment of haemophilia A and B.

Table 25.4 Variants of von Willebrand disease.

Table 25.5 Comparative laboratory findings in types of von Willebrand disease.

Table 25.6 Main causes of DIC.

Chapter 27

Table 27.1 Interventions that reduce the risk of acute anaemia and haemorrhage in acute haemorrhage and critical care.

Table 27.2 Platelet thresholds for prophylactic and therapeutic platelet transfusion.

Table 27.3 Summary of FFP RCTs in critically ill patient groups.

Table 27.4 Comparison of FFP and PCC, cryoprecipitate and fibrinogen concentrate.

Table 27.5 Studies evaluating the safety and efficacy of fibrinogen concentrate in major surgery.

Chapter 28

Table 28.1 Description of TEG parameters.

Table 28.2 Comparison of TEG and ROTEM variables.

Table 28.3 Modifications to ROTEM and interpretation.

Chapter 30

Table 30.1 Normal haemoglobins.

Table 30.2 Advantages and disadvantages of different types of blood transfusion in sickle cell disease.

Table 30.3 Assessment of iron overload.

Chapter 31

Table 31.1 HIT issues relevant to transfusion medicine.

Table 31.2 HIT viewed as a clinical–pathological syndrome.

Table 31.3 The 4Ts pretest probability score.

Table 31.4 PF4‐dependent antigen assays (immunoassays).

Table 31.5 A comparison of two classes of anticoagulant used to treat HIT.

Chapter 32

Table 32.1 Classification of severe combined immunodeficiency.

Table 32.2 Patterns of infection as a guide to selection of immunological tests in suspected immune deficiency.

Table 32.3 Use of IVIg as an immunomodulatory agent.

Table 32.4 Adverse effects of intravenous versus subcutaneous immunoglobulin.

Chapter 33

Table 33.1 Formulation of red blood cell anticoagulant‐preservative solutions.

Chapter 35

Table 35.1 Intravenous iron formulations.

Chapter 36

Table 36.1 Seven key clinical trials of blood transfusion in adults.

Table 36.2 Clinical practice guidelines for blood transfusion.

Chapter 37

Table 37.1 Data variables used to support patient blood management.

Table 37.2 Clinical outcomes to assess in a PBM programme.

Chapter 38

Table 38.1 Overview of voluntary accreditation/registry organisations (see individual websites to identify accredited centres, laboratories and registries as these data change often).

Chapter 40

Table 40.1 Human haemopoietic progenitor cells (HPCs).

Table 40.2 Stem cell laboratory processing procedures.

Chapter 41

Table 41.1 Classification of indications for blood and marrow transplants (www.bsbmt.org).

Table 41.2 Comparison of sources of stem cells.

Chapter 42

Table 42.1 Summary of large studies comparing cord blood transplant with haemopoietic stem cell (HSC) sources in paediatric patients with malignant disease.

Table 42.2 Summary of studies comparing cord blood transplant with haemopoietic stem cell (HSC) sources in adult patients.

Table 42.3 Advantages and disadvantages of different stem cell sources.

Table 42.4 Strategies to overcome the limitations of lower cell dose.

Chapter 44

Table 44.1 Indications for tissue allografts.

Chapter 45

Table 45.1 Considerations in determining which design approach to implement in transfusion trials.

Table 45.2 Comparison of study characteristics using either an efficacy or an effectiveness approach when designing a study.

Table 45.3 Types of randomised clinical trial (RCT) designs.

Chapter 47

Table 47.1 Example of a 2 × 2 table for diagnostic tests.

Table 47.2 Statistical terms used for diagnostic testing.

Table 47.3 Example of a 2 × 2 table and diagnostic test characteristics. Erez et al published a single‐centre retrospective study to generate a pregnancy adjusted disseminated intravascular coagulation (DIC) score, compared to a chart diagnosis of DIC as a gold standard [15]. In 684 women with abruption, 43 had DIC. The investigators used a cut‐off score of ≥26 to identify pregnant women with DIC and applied it to those with abruption as a sensitivity analysis.

Table 47.4 Descriptive statistics. Definitions and example calculation.

Table 47.5 Considerations for data analysis.

Table 47.6 Examples of considerations for data analysis.

Table 47.7 Commonly used parametric, nonparametric and regression statistics.

Table 47.8 Comparison of fixed and random effects models in meta‐analyses.

Chapter 48

Table 48.1 Summary of economic evaluation designs.

List of Illustrations

Chapter 01

Figure 1.1 James Blundell.

Figure 1.2 Karl Landsteiner.

Figure 1.3 The range of transfusion medicine.

Figure 1.4 Patrick Mollison.

Figure 1.5 Blood donation.

Figure 1.6 Risks of transfusion‐transmitted infections over time.

Figure 1.7 Paling scale of transfusion risk.

Figure 1.8 Red blood cell antigens.

Figure 1.9 DNA sequence.

Figure 1.10 RBC transfusion.

Figure 1.11 Trials examining the RBC transfusion threshold.

Figure 1.12 Sickle cell anaemia.

Figure 1.13 Cryopreservation in liquid nitrogen.

Figure 1.14 CRISPR technology allows targeted excision of DNA.

Figure 1.15 Cellular therapies of the future.

Chapter 02

Figure 2.1 Basic structure of an immunoglobulin molecule. Domains are held in shape by disulfide bonds, though only one is shown. CH1–3, constant domains of an H chain; C

L

, constant domain of a light chain; V

H

, variable domain of an H chain; V

L

, variable domain of a light chain.

Figure 2.2 The different pathways for complement activation. MBL, mannan‐binding lectin; MASP, MBL‐associated serine protease.

Chapter 03

Figure 3.1 Diagram of the oligosaccharides representing H, A, B, Le

a

and Le

b

antigens and the biosynthetic precursor of Hand Le

a

. R, remainder of molecule.

Figure 3.2 Diagrammatic representation of the Rh genes,

RHD

and

RHCE

, shown in opposite orientations as they appear on the chromosome, and of the two Rh proteins in their probable membrane conformation, with 12 membrane‐spanning domains and six extracellular loops expressing D, C/c and E/e antigens.

Chapter 04

Figure 4.1 Map of the human leucocyte antigen complex. HSP, heat‐shock protein; TNF, tumour necrosis factor.

Figure 4.2 HLA class I molecule. β

2

‐m, β

2

‐microglobulin.

Figure 4.3 HLA class II molecule.

Figure 4.4 Expression of HLA‐DRB genes.

Figure 4.5 An example of a current HLA nomenclature.

Figure 4.6 HFE molecule. β

2

‐m, β

2

‐microglobulin.

Chapter 05

Figure 5.1 Representation of the platelet membrane and the glycoproteins (GP) on which the human platelet antigens (HPA) are localised. From left to right are depicted GPIa/IIa, GPIIb/IIIa, CD109 and GPIb/IX/V. The molecular basis of the HPAs is indicated by black dots, with the amino acid change in single‐letter code and by residue number in the mature protein.

Figure 5.2 MAIPA assay. (1) Human serum and murine monoclonal antibody (MoMab) directed against glycoprotein being studied, e.g. GPIIb/IIIa are sequentially incubated with target platelets: in (a) the test serum contains anti‐HPA‐1a and in (b) no platelet antibodies are present. (2) After incubation, a trimeric (a) or dimeric (b) complex is formed. Excess serum antibody and MoMab are removed by washing. (3) The platelet membrane is solubilised in nonionic detergent, releasing the complexes into the fluid phase; particulate matter is removed by centrifugation. (4) The lysates containing the glycoprotein/antibody complexes are added to wells of a microtitre plate previously coated with goat anti‐mouse antibody. (5) Unbound lysate is removed by washing and enzyme‐conjugated goat antihuman antibody is added. (6) Excess conjugate is removed by washing and substrate solution is added. Cleavage of substrate, i.e. a colour reaction, indicates binding of human antibody to target platelets.

Chapter 06

Figure 6.1 Comparison of weak D and partial D with a normal D‐positive RBC. The circles represent the RBC membrane, the rectangles represent an RhD protein and the numbers above each RhD protein are a stylised representation of different D epitopes on the protein. The D epitopes are arbitrarily numbered 1, 2 and 3. The number of antigens and epitopes, as well as the size of the RhD protein, is not to scale. In this example, eight D antigens on the RBC surface are schematically shown as normal, and each D antigen has three D epitopes. In reality, the number of D antigens ranges from 10 000 to 25 000 and more than 30 D epitopes are expressed on the D antigen. The weak D RBC features D antigens with the full complement of D epitopes but the number of D antigens is reduced compared to normal. The partial D RBC demonstrates the normal number of D epitopes but each protein is lacking at least one D epitope. The partial D type DVI demonstrates both weak D and partial D features.

Figure 6.2 Indirect immunoglobulin test.

Figure 6.3 Column‐agglutination technology for blood grouping and antibody screening. Samples may consist of patient cells and reagent antisera or reagent red cells and patient serum/plasma. Positive results are seen in the first and last columns, the other columns show negative reactions.

Figure 6.4 Solid‐phase blood grouping technology.

Chapter 07

Figure 7.1 Flow diagram illustrating a possible approach for the management and investigation of an acute transfusion reaction.

Chapter 08

Figure 8.1 Pathophysiology of the haemolytic transfusion reaction (HTR). ADCC, antibody‐dependent cell‐mediated cytotoxicity; MAC, membrane attack complex; NK, natural killer.

Chapter 10

Figure 10.1 Chest x‐rays of a patient with transfusion‐related acute lung injury. (a) One day before a platelet transfusion and (b) shortly after transfusion showing diffuse bilateral shadowing of the lungs and a normal‐sized heart.

Figure 10.2 Thin sections of fixed lung from a patient with transfusion‐related acute lung injury. There is acute diffuse alveolar damage with intra‐alveolar oedema and haemorrhage. There was no histological evidence of infection and all postmortem cultures (bacterial, viral and fungal) were negative. Magnification: (a) ×40, (b) ×440.

Chapter 12

Figure 12.1 The metaanalytic summary of randomised trials of leucocyte‐reduced red cell transfusions to mitigate post‐operative infection in colorectal cancer surgery is shown. The risk of infection is approximately 55% less in patients receiving leucocyte‐reduced red cells.

Figure 12.2 Meta‐analytic summary of randomised trials of autologous transfusions (either pre‐deposit, haemodilution or salvage) to mitigate post‐operative infection after surgery. The risk of infection is approximately 46% less in patients receiving autologous red cells [9].

Figure 12.3 Meta‐analytic summary of randomised trials of restrictive red cell transfusion thresholds (usually <70 g/L) to mitigate post‐operative infection in orthopaedic surgery. The risk of infection is 28% less in patients receiving red cells according to restrictive criteria [13].

Figure 12.4 The proportion of patients with infection as a function of the oldest red cell unit transfused in a randomised trial of washed, irradiated, leucocyte‐reduced red cells in paediatric cardiac surgery. The almost 10‐fold difference is unlikely to be totally explained by confounding, and suggests that older red cells, when transfused at doses of hundreds of millilitres per kilogram (as in infants), may be more immunomodulatory than shorter storage red cells, but these observational data require confirmation in a randomised trial [19].

Figure 12.5 Proportion of patients surviving after diagnosis is shown for younger patients (<50 years of age) with acute leukaemia randomised to washed, leucocyte‐reduced, ABO‐identical, irradiated red cells and platelets versus unwashed, leucocyte‐reduced, ABO‐identical irradiated transfusions (n=12 for washed versus 10 for unwashed). P=0.03.

Chapter 14

Figure 14.1 A typical time course of PTP. Purpura and severe thrombocytopenia occurred 5–10 days after a blood transfusion. The figure indicates the secondary antibody response of anti‐HPA‐1a, and the postulated transient appearance of either free HPA‐1a antigen in the plasma, which binds to HPA‐1a negative platelets, HPA‐1a/anti‐HPA‐1a immune complexes, platelet autoantibodies or cross‐reacting HPA‐1a antibodies.

Figure 14.2 Haematological course of a patient with posttransfusion purpura showing the onset of profound thrombocytopenia six days after a blood transfusion. Initial treatment with random platelet concentrates caused rigors and bronchospasm, and there was no platelet increment. There was no response to prednisolone (60 mg/day) or plasma exchange (2.5 L/day for three days), but there was a prompt remission following high‐dose IVIgG (30 g/day for three days).

Chapter 19

Figure 19.1 Timeline of critical haemovigilance events.

Chapter 22

Figure 22.1 (a) Production of leucocyte‐reduced (LR) red cell concentrates (RCC), fresh frozen plasma (FFP) and platelet‐rich plasma (PRP)‐intermediate platelet concentrates (PC). (b) Production of RCCs, plasma frozen within 24 hours of phlebotomy (PF24) and buffy coat (BC)‐intermediate PCs.

Chapter 23

Figure 23.1 The hospital transfusion process: Steps in the transfusion process, and the staff predominantly responsible for each step.

Figure 23.2 How to perform an identity check between the patient and blood component.

Figure 23.3 Bedside checking using an electronic system. The traditional method of pretransfusion bedside checking requires two nurses and checks of multiple items of written documentation. With barcode technology, a handheld computer reads a barcode on the patient wristband containing full patient details. The handheld computer checks that the patient details on the wristband barcode match those on the barcode (in the red box) on the compatibility label attached to the unit after pretransfusion testing. This barcode also contains the unique number of the unit, and is matched with the barcode number of the unit (top left of the bag) to ensure that the blood transfusion laboratory has attached the right compatibility label.

Figure 23.4 Warning message displayed when a physician at a University of Pittsburgh Medical Center (UPMC, Pittsburgh, PA) hospital attempts to order red cells using the computerised order entry system for a patient whose most recent haemoglobin value is in excess of the institutional guidelines.

Chapter 25

Figure 25.1 ‘Cascade’ model of coagulation.

Figure 25.2 Cell‐based model of coagulation. Coagulation is initiated on the surface of tissue factor (TF)‐bearing cell, generating small amounts of thrombin (FIIa). In the amplification phase, platelets and factors V, VIII and XI are activated. In the propagation phase, large amounts of thrombin are generated, leading to activation of fibrin and factor XIII and production of cross‐linked stable clot.

Figure 25.3 Schematic representation of thromboelastography (TEG

®

). 1. The R value (clotting time) represents the time it takes to initiate clot formation. It is a reflection of coagulation factor activity. 2. The alpha angle represents the thrombin burst and conversion of fibrinogen to fibrin. 3. The MA is maximal amplitude or clot strength derived from platelet function. 4. The K value (kinetics of clot formation) is the time from the end of R until the clot reaches 20 mm and represents the speed of clot formation. 5. LY30 lysis time measures the degree of fibrinolysis.

Chapter 26

Figure 26.1 Proposed schema for a massive transfusion protocol.

Figure 26.2 Losses of platelet concentration and plasma coagulation factor activity with pooling blood components in ratios.

Chapter 27

Figure 27.1 Forest plot summarising the odds ratios from RCTs evaluating the relationship between red cell transfusion and 30‐day mortality. Upper panel shows odds ratios from RCTs that have compared liberal versus restrictive transfusion thresholds in patients with symptomatic cardiac disease. Lower panel shows odds ratios from RCTs in patients without symptomatic disease. An increasing odds ratio indicates increasing risk of death with transfusion.

Chapter 28

Figure 28.1 Example TEG tracing.

Source:

Allen SR, Kashuk JL. Unanswered questions in the use of blood component therapy in trauma. Scand J Trauma Resus Emerg Med 2011;19:5. Original reprinted with permission from Hemoscope Corporation, Niles, IL.

Figure 28.2 University of Pittsburgh Medical Center Massive Transfusion Protocol.

Chapter 29

Figure 29.1 The indirect Donath–Landsteiner test for paroxysmal cold haemoglobinuria.

Figure 29.2 Algorithm for the investigation and management of patients with platelet refractoriness. DIC, disseminated intravascular coagulation; HLA, human leucocyte antigen; HPA, human platelet antigen.

Figure 29.3 Responses to platelet transfusions in a female patient with acute myeloblastic leukaemia undergoing remission induction therapy. There were poor responses to the initial platelet transfusions and the patient was found to have human leucocyte antigen (HLA) antibodies. There were improved responses to platelet transfusions from HLA‐matched donors.

Figure 29.4 Recommendations for ABO type of blood components in ABO‐incompatible bone marrow/peripheral blood progenitor cell transplants. RBC, red blood cell.

Chapter 31

Figure 31.1 Pathogenesis of HIT. Platelet activation, either via binding of heparin to platelets (PLT) or by other mechanisms (e.g. surgery), leads to release of platelet factor 4 (PF4) from platelet α‐granules. PF4/heparin complexes form, which in some patients triggers generation of platelet‐activating anti‐PF4/heparin antibodies (‘HIT antibodies’), predominantly of the IgG class. Multimolecular complexes composed of PF4, heparin and IgG are formed on platelet surfaces, leading to cross‐linking of the platelet Fc receptors (FcγRIIa). This produces potent platelet activation, including conformational changes in the platelet fibrinogen receptors (GPIIb/IIIa), resulting in platelet aggregation; procoagulant changes in the platelet surface – including generation of procoagulant, platelet‐derived microparticles (MPs) – leading to thrombin generation; and further release of granule constituents such as PF4, triggering even more IgG‐mediated platelet activation. Further, PF4 binds to endothelial cell (EC) heparan sulfate, resulting in HIT antibody binding to endothelial PF4/heparin complexes and, possibly, EC activation and expression of endothelial tissue factor (open rectangle), contributing further to thrombin generation. Thrombin activates platelets and endothelium, leading to thrombosis.

Figure 31.2 Iceberg model using published data [11]. The central ‘iceberg’ depicts three different antibody reaction profiles, as defined by a platelet activation test (HIPA) and two ELISAs (IgG‐ELISA, poly‐ELISA). The table on the far left shows the pretest probability scores (4Ts) for the three different antibody reaction profiles, as well as for patients who test negative in both ELISAs (bottom row of 4Ts table). On the far right, the corresponding results in the particle gel immunoassay (PaGIA) are shown. The data demonstrate that the sensitivity of the PaGIA for definite HIT (35 patients depicted as the ‘tip of the iceberg’) is only 94% (33/35). At the other extreme, ˜5% of the patients who have no antibodies by ELISA will test positive in the PaGIA (17/376). ELISA, enzyme‐linked immunosorbent assay (or enzyme‐immunoassay); HIT, heparin‐induced thrombocytopenia; PaGIA, particle gel immunoassay.

Chapter 32

Figure 32.1 Major events in T‐cell development and sites of mutations leading to immunodeficiencies. T‐cell development in the thymus from a progenitor cell proceeds sequentially from a double‐negative state (CD4–, CD8–) to mature T‐cells expressing either CD4 or CD8. Stages of T‐cell differentiation associated with mutations and deficiencies of proteins are depicted in boxes.

Figure 32.2 Major events in B‐cell development and sites of mutations leading to immunodeficiencies. B‐cell development in the bone marrow proceeds from a progenitor cell sequentially to plasma cells in the periphery. Stages of B‐cell differentiation associated with mutations and deficiencies of proteins are depicted in boxes.

Figure 32.3 Cumulative probability of survival in SCID patients, according to donor source (related or unrelated donor) and HLA matching, and year of transplantation.

Figure 32.4 Immunomodulatory actions of intravenous immunoglobulin.

Chapter 34

Figure 34.1 Computerised Physician Order Entry Page for Red Blood Cells.

Figure 34.2 Transfusion variance report.

Figure 34.3 The rainbow draw.

Figure 34.4 Anaemia management algorithm.

Figure 34.5 Benchmarking report.

Chapter 35

Figure 35.1 The three‐pillar, nine‐field matrix of perioperative patient blood management. This matrix, designed for the Western Australia Patient Blood Management Program, highlights the multiple patient blood management strategies that may be considered in the perioperative period in a patient/procedure‐specific context. GI, gastrointestinal.

Figure 35.2 Flowchart for anaemia classification. ACI, anaemia of chronic inflammation; ID, iron deficiency; IDA, iron deficiency anaemia; TSAT, transferrin saturation.

Figure 35.3 Major haemorrhage protocol (Royal Marsden NHS Foundation Trust).

Figure 35.4 Pathways to surgery for patients with preoperative anaemia. IV, intravenous; PBM, patient blood management; PO, per os.

Chapter 36

Figure 36.1 Best practices alert (BPA) screenshots at Stanford University Medical Centrr (SUMC). Screenshot from an electronic physician order entry (POE) for blood transfusion in adult patients at Stanford Hospital and Clinics (SHC) illustrates an ‘interruptive alert’ as a reminder for the merits of a restrictive transfusion practice versus liberal transfusion practice. An acknowledgment/exception field allows the physician to provide the indication for transfusion (acute bleeding, haemoglobin <80 g/L in the acute coronary syndrome or postcardiothoracic surgery patient, other clinical scenario) if such clinical scenarios were not updated in the problem list. The BPA for paediatric patients at Lucille Packard’s Children’s Hospital (LPCH) triggers only for children ages 1–18 years with haemoglobin >70 g/L who are normotensive in the last six hours. The alert did not trigger in patients from cardiac, haematology‐oncology and neonatal ICU wards.

Figure 36.2 Trends in blood utilisation. Blood components issued to patients at Stanford Health Care. Transfusion of red cells decreased by 24% from 2009 through 2014.

Chapter 37

Figure 37.1 Haemoglobin (Hb) triggers (the Hb before transfusion) and Hb targets (the Hb after transfusion) are shown from the five large randomised trials [2,4,19–21] that compared restrictive and liberal transfusion strategies. Although the trial results advocate for the use of a restrictive transfusion strategy, with Hb triggers of 70–80 g/L for most patients, the Hb target concentration in the restrictive group was 85–95 g/L. When this finding is considered in the Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS) trial, for example, the two groups compared (Hb trigger 80 versus 100 g/L) had actual daily average Hb concentrations that were 95 in the restrictive group and 110 g/L in the liberal group.

Figure 37.2 Effect of a patient blood management programme (PBM) on red blood cell utilisation. (a) The number of red cell units/month that were ordered with a preceding haemoglobin (Hb) >80 g/L is shown over a five‐year period. With a multifaceted PBM programme that includes education, and computerised provider order entry with clinician decision support and a best practice alert, we achieved a 54% decrease in out‐of‐guideline red cell transfusions between the months of January 2009 and November 2013. (b) We also saw an overall decrease in red cell utilisation for eight out of 10 surgical services and an overall decrease in surgical blood utilisation of 14.3% over the same time period.

Figure 37.3 Comparison of mean transfusion haemoglobin (Hb) triggers and targets for all surgeons and anaesthesiologists who had 10 or more patients in the anaesthesia information management system (AIMS) database. The mean Hb triggers are designated by the left edge of the red bars and the mean Hb targets by the right edge of the red bars. The span between the lowest and highest Hb triggers was 26 g/L for surgeons and 24 g/L for anaesthesiologists. The span between lowest and highest Hb targets was 30 g/L for surgeons and 28 g/L for anaesthesiologists.

Figure 37.4 These data were taken from the computerised provider order entry system. Individual physicians (y‐axis) were compared by the number of red blood cell orders placed (x‐axis) over a three‐month time period, along with the percentage of orders placed by haemoglobin (Hb) trigger. The proportion of orders for which the most recent Hb preceding the order was <70 g/L is shown in green, 70–79 g/L in yellow and ≥80 g/L in red. An accompanying table for each department is provided showing the five‐digit codes on the y‐axis correspond to the names of attending physicians.

Figure 37.5 Intraoperative blood component requirements are plotted as a function of Case Mix Index (CMI). Left side: CMI is represented by the weighted Medicare Severity Diagnosis‐Related Group (MS‐DRG Weight). Right side: CMI is represented by the weighted All Patient Refined Diagnosis‐Related Group (APR‐DRG Weight). The data show a clear relationship between a higher CMI value and greater intraoperative transfusion requirements for red blood cells, fresh frozen plasma (FFP) and platelets (PLTS). Differences in CMI values among transfusion requirement groups are significant for all six analyses shown (P < 0.0001).

Chapter 38

Figure 38.1 Timeline of involvement of different organisations in the field of cellular therapy. AABB (formerly the American Association of Blood Banks); CAP, College of American Pathologists; FACT, Foundation for the Accreditation of Cellular Therapy; EU, European Union; FDA, US Food and Drug Administration; JACIE, Joint Accreditation Committee (ISCT and EBMT); NMDP, National Marrow Donor Program.

Figure 38.2 Comparison of the types of HSCT (a) and source of grafts (b) in Europe and the US in 2013 and 2012, respectively. HPC, haematopoietic progenitor cells; UCB, umbilical cord blood unit; URD, unrelated donor.

Figure 38.3 Regulatory environment for haematopoietic stem cell transplantation. Note that this figure does not reflect all potential regulatory reporting requirements for transplantation centres.

Chapter 39

Figure 39.1 Kinetics of plasma exchange.

Chapter 43

Figure 43.1 Generation of CAR or TCR gene‐modified T‐cells for cancer immunotherapy. Retroviral and lentiviral vectors encoding CAR or TCR molecules can be used to redirect the specificity of human T‐cells. CAR molecules recognise proteins that are expressed on the surface of cancer cells. TCR molecules can recognise peptides that are derived from intracellular proteins, including mutated proteins.

Figure 43.2 Schematic illustrating mispairing with endogenous TCR chains by the introduced TCR chains following retroviral TCR gene transfer.

Figure 43.3 Ligands controlling NK cell activation and triggering.

Figure 43.4 Capping of KIR molecules on NK cell. Anti‐KIR antibody (

green

) shows co‐localisation of KIR and MHC class I molecules at the synapse between the NK and autologous normal cell. In contrast, the MHC‐negative tumour cell fails to initiate capping of the KIR molecules.

Chapter 45

Figure 45.1 Observational study designs: case–control and cohort studies.

Figure 45.2 Design approaches for randomised controlled trials. (a) Randomised two‐group parallel design: subjects randomly assigned to treatment A or B. (b) Factorial design: all subjects randomly assigned to treatment A, treatment B, treatment A + B or no treatment. (c) Randomised crossover design: subjects randomly assigned to treatment A followed by treatment B (after wash‐out period) or treatment B followed by treatment A. (d) Randomised cluster design: all subjects in one group/area (e.g. by physician, by hospital, by ward) are assigned to treatment A or B.

Chapter 46

Figure 46.1 A hypothetical forest plot.

Figure 46.2 A guide for judging the validity of evidence for treatment decisions from different types of studies and reviews.

Figure 46.3 The forest plot for total arterial thromboembolic events.

Chapter 47

Figure 47.1 Measurements of disease/case frequency.

Figure 47.2 Example of the use of a Fagan nomogram. You wish to assess whether a young male seen in your clinic has splenomegaly as a potential reason for thrombocytopenia. Assuming the prevalence of splenomegaly is 3% in the general population, we would normally take the pretest probability as 0.03. However, on history, he has been complaining of early satiety and was referred to you with lymphadenopathy. You assume his pretest probability is higher at 0.15. Now you wish to use percussion of Traube’s space (a physical examination manoeuvre) to try and investigate this further. If this test is positive, it has a positive likelihood ratio of 2.21. If this test is negative, it has a negative likelihood ratio of 0.53. The thick line on the nomogram demonstrates the post‐test probability if the test were positive and the thin line demonstrates the post‐test probability if the test were negative. This patient would have a post‐test probability of 0.3 if positive and 0.085 if negative.

Figure 47.3 Example of a forest plot. Meta‐analysis of the weighted mean difference in the 1‐hour corrected count increments of whole blood‐derived (WBD) platelets compared to apheresis platelet concentrates (APC).

Chapter 48

Figure 48.1 Representative costs associated with transfusion. Costs associated with transfusion can be categorised by the order in which they are experienced: pre‐transfusion, transfusion and post‐transfusion. Within each of these categories, direct medical, direct nonmedical and intangible costs are borne by donors (D), blood suppliers (S), hospitals (H) and patients (P). For hospitals that both collect and transfuse blood products, both the supplier and hospital costs would be incorporated. An economic evaluation may choose to focus on one of these perspectives and some or all of these cost categories.

Figure 48.2 Illustration of cost‐effectiveness outcomes. Each quadrant of this graph represents one of four potential scenarios resulting from a cost‐effectiveness analysis comparing one proposed strategy to a baseline strategy. The lower right quadrant (1) represents a scenario where the change in costs (∆C) is negative (the cost of the proposed is less than the cost of the baseline), and the change in effectiveness (∆E) is positive (the effectiveness of the proposal is greater than the effectiveness of the baseline). Any scenario falling in this quadrant will be cost saving and considered dominant over the baseline. The upper right quadrant (2) represents the situation where both ∆C and ∆E are positive. If the incremental cost‐effectiveness ratio (ICER), calculated as shown, falls below a given threshold (e.g. $50 000/QALY), the proposed strategy is considered cost effective. However, if the ICER is greater than the threshold, the proposed strategy would not be considered cost effective. The upper left quadrant (3) represents the scenario where ∆C is positive and ∆E is negative. Any scenario falling in this quadrant would be excluded, since neither of the dimensions (cost or effectiveness) is enhanced under the proposed strategy. Finally, in the lower left quadrant (4), ∆C and ∆E are both negative. This is not a commonly considered scenario, since the proposed strategy being evaluated is generally either more costly or less effective than a baseline.

Figure 48.3 Illustration of example calculations and comparisons for cost‐effectiveness ratios. In this example, the decision involves four mutually exclusive strategies, where Strategy 1 represents a baseline, and Strategies 2–4 represent alternative proposals. Costs and effectiveness are shown for each of these strategies, and the proposed strategies are arranged in order of increasing effectiveness. The average cost‐effectiveness ratio (ACER) for Strategies 2–4 is calculated using Strategy 1 as comparison group, while the incremental cost‐effectiveness ratio (ICER) is calculated using the next lowest effectiveness strategy as the comparison (Strategy 4 uses Strategy 3 as comparison, Strategy 3 uses Strategy 2 as comparison and Strategy 2 uses Strategy 1 as comparison). The ICER values are then compared to determine if particular strategies can be eliminated. The top table shows that Strategy 3 is ‘strongly dominated’ by Strategy 4: Strategy 3 is less effective and more costly than Strategy 4. Thus, Strategy 4 is clearly preferable to Strategy 3, and we eliminate Strategy 3 from our list of potential strategies (second table). The ICERs are then recalculated, using Strategy 2 as the comparison group (next lower effectiveness) for Strategy 4. These results show that Strategy 2 is ‘weakly dominated’ by Strategy 4: the ICER for Strategy 4 is less than the ICER for Strategy 2 (third table). This indicates that the marginal cost of obtaining the effectiveness associated with Strategy 2 is greater than the marginal cost of an alternative. Strategy 2 is thus eliminated (fourth table).

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Practical Transfusion Medicine

FIFTH EDITION

Edited By

Michael F. Murphy, MD, FRCP, FRCPath, FFPath

Professor of Blood Transfusion MedicineUniversity of OxfordConsultant HaematologistNHS Blood and Transplant and Department of Haematology, Oxford University HospitalsOxford, UK

David J. Roberts, MB, ChB, D.Phil, FRCPath

Professor of HaematologyUniversity of OxfordConsultant HaematologistNHS Blood and Transplant and Department of Haematology, Oxford University HospitalsOxford, UK

Mark H. Yazer, MD

Professor of PathologyUniversity of PittsburghAdjunct Professor of Clinical ImmunologyUniversity of Southern DenmarkOdense, DenmarkMedical DirectorRBC Serology Reference Laboratory, ITXM Centralized Transfusion ServiceAssociate Medical DirectorITXM Centralized Transfusion ServicePittsburgh, USA

This edition first published 2017

© 2001, 2005, 2009, 2013 by John Wiley & Sons Ltd

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The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting scientific method, diagnosis, or treatment by physicians for any particular patient. The publisher and the authors make no representations or warranties with respect to the accuracy and completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of fitness for a particular purpose. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. Readers should consult with a specialist where appropriate. The fact that an organization or website is referred to in this work as a citation and/or potential source of further information does not mean that the authors or the publisher endorses the information the organization or website may provide or recommendations it may make. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this works was written and when it is read. No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the authors shall be liable for any damages arising herefrom.

Library of Congress Cataloging‐in‐Publication Data

Names: Murphy, Michael F. (Michael Furber), editor. | Roberts, David J. (David John) (Consultant hematologist), editor. | Yazer, Mark H., editor.Title: Practical transfusion medicine / edited by Michael F. Murphy, David J. Roberts, Mark H. Yazer.Description: Fifth edition. | Hoboken, NJ : John Wiley & Sons Inc., 2017. | Preceded by Practical transfusion medicine / edited by Michael F. Murphy, Derwood H. Pamphilon, Nancy M. Heddle. 4th ed. 2013. | Includes bibliographical references and index.Identifiers: LCCN 2016053360 | ISBN 9781119129417 (cloth) | ISBN 9781119129448 (Adobe pdf) | ISBN 9781119129424 (epub)Subjects: | MESH: Blood Transfusion | Blood Grouping and Crossmatching | Hematopoietic Stem Cell Transplantation | Blood Preservation | Cross Infection–prevention & controlClassification: LCC RM171 | NLM WB 356 | DDC 615.3/9–dc23LC record available at https://lccn.loc.gov/2016053360

List of Contributors

Louis H. AlarconProfessor of Departments of Surgery and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, USA

Jean Pierre AllainNHS Blood and Transplant and Division of Transfusion Medicine, Department of Hematology, University of Cambridge, Cambridge, UK

Imelda BatesProfessor of Clinical Tropical Haematology, Liverpool School of Tropical Medicine, Liverpool, UK

Ravishankar Rao BaikadyConsultant in Anaesthesia, The Royal Marsden, NHS Foundation Trust, London, UK

Neil BlumbergDepartment of Pathology and Laboratory Medicine, University of Rochester; Blood Bank/Transfusion Service of Strong Memorial Hospital, Rochester, USA