Practical Transfusion Medicine

Description

Practical Transfusion Medicine Practical Transfusion Medicine, Sixth Edition The pace of change in transfusion medicine is relentless, with new scientific and technological developments and continuing efforts to improve transfusion practice. This sixth edition of Practical Transfusion Medicine has been updated significantly to reflect the rapid changes in transfusion medicine since the fifth edition was published in 2017. The primary purpose of this edition remains the same as the first: to provide a comprehensive guide to transfusion medicine. This book contains more depth of information than standard handbooks on transfusion medicine, whilst being more concise and approachable than a standard reference text. This book covers the principles of transfusion medicine, the complications of transfusion, practice in blood centres and hospitals and clinical transfusion practice. This sixth edition includes a new section on patient blood management, cellular and tissue therapy, organ transplantation and the development of the evidence base for transfusion. It also features a new chapter on transfusion-associated circulatory overload to underline its importance as a complication of transfusion, and a reconfiguration of the section on clinical transfusion practice to allow consideration of the transfusion management of medical, surgical and haematology patients with and without bleeding. This sixth edition of Practical Transfusion Medicine provides accessible and comprehensive coverage of the field of transfusion medicine. It is a standalone text that will be useful to clinical and scientific staff: not only for trainees who require an overview of the field, but also for established practitioners who are involved in some aspect of transfusion medicine and require a comprehensive, accessible reference book. Cover Title Page Copyright Page Contents List of Contributors Preface to the Sixth Edition Chapter 1 Introduction: Two Centuries of Progress in Transfusion Medicine 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 Chapter 2 Essential Immunology for Transfusion Medicine Cellular Basis of the Immune Response Innate Immune Cells Adaptive Immune Cells B-Cell Activation and T-Cell-Dependent Antibody Formation Humoral Immune Response Basis of Antibody Variability Antibody Effector Functions Red Blood Cell Antibodies Illustrating These Principles Antibody and Complement-Mediated Blood Cell Destruction Clinical Aspects Related to Alloimmunisation against Blood Cell Antigens Acknowledgement References Further Reading Chapter 3 Human Blood Group Systems The ABO System Clinical Significance Biosynthesis and Molecular Genetics H, the Biochemical Precursor of A and B The Rh System Rh Genes and Proteins D Antigen Anti-D Prediction of Fetal Rh Phenotype by Molecular Methods C and c, E and e Other Rh Antigens Other Blood Group Systems Kell System Duffy System Kidd System MNS System Biological and Clinical Significance of Blood Group Antigens References Further Reading Chapter 4 Human Leukocyte Antigens 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 HLA Nomenclature, Gene Polymorphism and Molecular HLA Typing PCR Sequence-Specific Priming PCR Sequence-Specific Oligonucleotide Probing DNA Sequencing-Based Typing Formation of HLA Antibodies HLA Antibody Detection CDC/Microlymphocytotoxicity Assay Solid-Phase Antibody Detection Assays Crossmatching for Compatibility Evaluation Physical Crossmatches Virtual Crossmatches HLA and Solid Organ Transplantation HLA and Haematopoietic Stem Cell Transplantation HLA and Blood Transfusion HLA and Disease Association HLA and Pharmacogenomics Acknowledgements References Further Reading Chapter 5 Platelet and Neutrophil Antigens Antigens on Platelets and Neutrophils Human Platelet Antigens Inheritance and Nomenclature Typing for HPAs Platelet Isoantigens, Autoantigens and Drug-Dependent Antigens Detection of HPA Alloantibodies Clinical Significance of HPA Alloantibodies Fetal and Neonatal Alloimmune Thrombocytopenia Human Neutrophil Antigens HNA-1 HNA-2 HNA-3 HNA-4 and HNA-5 Detection of Neutrophil Antibodies Clinical Significance of HNA Antibodies Neonatal Alloimmune Neutropenia FNHTR and TRALI Autoimmune Neutropenia Persistent Post–Bone Marrow Transplant Neutropenia Drug-Induced Neutropenia References Further Reading Chapter 6 Pretransfusion Testing and the Selection of Red Cell Products for Transfusion Determining the Recipient’s ABO Group and Screening for Unexpected Antibodies Clerical Check and Verification of Recipient’s Identity Determining the Recipient’s ABO Group Determining the Recipient’s D Type Difficulties in D Typing: Weak and Partial D Antibody Screening and Identification Antibody Detection Methods Liquid-Phase (‘Tube’) Systems Column-Agglutination Systems Solid-Phase Systems Autoantibodies Pretransfusion Molecular Testing Crossmatching Techniques Crossmatch Techniques for Patients without Current or Historical Antibodies Crossmatch Techniques for Patients with Current or Historical Antibodies Selection of Red Cells for Transfusion Selecting ABO-Compatible Red Cells Selecting D-Compatible Red Cells Clinical Significance of Unexpected Antibodies Use of Uncrossmatched Red Cells Selection of Platelets and Plasma Components References Further Reading Chapter 7 Investigation of Acute Transfusion Reactions Understanding the Clinical Presentation and Differential Diagnosis Patient History Medications Type of Blood Component Being Transfused Was Fever Present? Volume of Component Transfused Other Considerations General Approach for Investigation and Treatment of Acute Transfusion Reactions Action to Be Taken on the Clinical Unit Action to Be Taken in the Laboratory Algorithm References Further Reading Chapter 8 Haemolytic Transfusion Reactions Definition of a Haemolytic Transfusion Reaction Pathophysiology of Haemolytic Transfusion Reactions Antibody-Mediated haemolysis Antigen–Antibody Interactions Characteristics of the Antibody and Antigen Complement Activation Fc Receptor Interactions Cytokines Antibody Specificities Associated with Haemolytic Transfusion Reactions The Pathophysiology of Hyperhaemolysis (aka Post-Transfusion Haemophagocytic Syndrome) Acute Haemolytic Transfusion Reactions Aetiology and Incidence Symptoms and Signs Complications Immediate Management of Suspected Acute Haemolytic Transfusion Reactions Investigation of Suspected Acute Haemolytic Transfusion Reactions Other Reactions Characterised by Haemolysis Management of a Confirmed Acute Haemolytic Transfusion Reaction Prevention of Acute Haemolytic Transfusion Reactions Delayed Haemolytic Transfusion Reactions Aetiology and Incidence Signs and Symptoms Management Investigation of Suspected Delayed Haemolytic Transfusion Reactions (see Chapter 7) Prevention Haemolysis Resulting from Haemopoietic Stem Cell Transplantation (see Chapter 41) Delayed Haemolysis Following Organ Transplantation (Passenger Lymphocyte Syndrome) Haemophagocytic/Hyperhaemolytic Transfusion Reactions and Haemolytic Transfusion Reactions in Sickle Cell Disease Acute Haemolysis from ABO-Incompatible Platelet Transfusions References Further Reading Chapter 9 Febrile and Allergic Transfusion Reactions Febrile Non-haemolytic Transfusion Reactions Clinical Presentation Differential Diagnosis Frequency Pathogenesis Management of Febrile Non-haemolytic Transfusion Reactions Prevention of Febrile Non-haemolytic Transfusion Reactions Allergic Transfusion Reactions Clinical Presentation Differential Diagnosis Frequency Pathogenesis Management Prevention References Further Reading Chapter 10 Transfusion-Associated Circulatory Overload Definition Incidence and Outcomes Clinical Manifestations Pathophysiology Risk Factors Extremes of Age Fluid Balance Renal and Cardiac Dysfunction Transfusion Volume and Rate Type of Product Differential Diagnosis and Evaluation Patient Characteristics and Onset of Symptoms Symptoms Laboratory Assessment Radiological Evaluation Echocardiography Invasive Measurements Treatment and Prevention References Further Reading Chapter 11 Transfusion-Related Acute Lung Injury (TRALI) Definition Incidence, Outcomes and Recipient Risk Factors Clinical Manifestations Differential Diagnosis Pathogenesis Two-Hit Model Susceptibility Hit and Potential Role for Perioperative Third Hit Immune Cell Involvement Potential Therapeutic Avenues Mitigation Strategies Patient Management Reporting References Further Reading Chapter 12 Purported Adverse Effects of ‘Old Blood’ Randomised Controlled Trials of Red Blood Cell Storage Duration Recent Randomised Controlled Trials of Red Blood Cell Storage Duration in Children Recent Randomised Controlled Trials of Red Blood Cell Storage Duration in Adults Systematic Reviews and Secondary Analyses of Randomised Controlled Trials of Red Blood Cell Storage Duration Future Research Conclusions References Further Reading Chapter 13 Transfusion-Induced Immunomodulation 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 Chapter 14 Transfusion-Associated Graft-versus-Host Disease and Microchimerism Transfusion-Associated Graft-versus-Host Disease Pathogenesis Clinical Features Prevention Blood Component Factors Patients at Increased Risk Guidelines and Requirements for Irradiated Products Universal Irradiation Pathogen Inactivation Haemovigilance Transfusion-Associated Microchimerism Clinical Data References Further Reading Chapter 15 Posttransfusion Purpura Definition Incidence Clinical Features Differential Diagnosis Laboratory Investigations Pathophysiology Management Prevention of Recurrence of Posttransfusion Purpura References Further Reading Chapter 16 Heparin-Induced Thrombocytopenia Pathogenesis Epidemiology Heparin-Induced Thrombocytopenia: A ‘Clinicopathological’ Syndrome Iceberg Model Clinical Picture Thrombocytopenia Timing Thrombosis and Other Sequelae Pretest Probability Scores Laboratory Testing Platelet Activation Assays Platelet Factor 4–Dependent Immunoassays (Antigen Assays) Treatment Rapidly Acting, Non-heparin Anticoagulants Prevention of Warfarin-Induced Venous Limb Gangrene Management of Isolated Heparin-Induced Thrombocytopenia Adjunctive Therapies Repeat Heparin Exposure Vaccine-Induced Immune Thrombotic Thrombocytopenia References Further Reading Chapter 17 Transfusion-Transmitted Infections 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 Viruses Bacteria Parasitic Diseases Prions References Further Reading Chapter 18 Bacterial Contamination Incidence of Bacterial Contamination Blood Components Implicated in Adverse Transfusion Reactions Platelet Concentrates Red Blood Cells Plasma and Cryoprecipitate Contaminant Bacterial Species Platelet Concentrates Red Blood Cells Plasma and Cryoprecipitate Sources of Contamination Blood Donor Blood Collection and Production Processes Investigation of Transfusion Reactions Prevention Strategies Donor Screening Skin Disinfection First Aliquot Diversion Single-Donor Apheresis versus Pooled Platelet Concentrates Bacterial Detection Methods Pretransfusion Detection Methods Used by Blood Centres Bacterial Detection Methods to Be Used Prior to Transfusion Pathogen Reduction Technologies References Further Reading Chapter 19 Emerging Infections and Transfusion Safety 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 Pandemic Preparedness References Further Reading Chapter 20 Regulatory Aspects of Blood Transfusion The Components of Blood Regulation Guiding Principles and Law Standards Application and Enforcement of Regulations Inspection/Accreditation/Licensing Enforcement Threat Surveillance Vigilance: Haemovigilance/Feedback/Market Surveillance The Regulatory Bodies National Statutory Bodies with Powers of Enforcement Supranational Agencies with Statutory Powers Supranational Agencies with Treaty-Defined Powers and Remits Professional Organisations within the Blood Transfusion Community Itself That Set or Define Professional Standards Stakeholder Input into Regulatory Decision Making The Role of Blood Transfusion Agencies and Health Professionals vis-à-vis Regulatory Agencies References Further Reading Chapter 21 The Role of Hemovigilance in Transfusion Safety Haemovigilance System Organisational Structures Scope, Breadth and Analysis of Reporting Scope Analysis Standardisation of Data Elements for Data Capture Data Management Haemovigilance System Limitations Lessons Learned from Haemovigilance Call to Action and Future Directions References Further Reading Chapter 22 Donors and Blood Collection Blood Donors: Altruistic, Directed, Payback and Paid Risks to the Blood Donor Donor Selection and Deferral Iron Deficiency in Blood Donors Men Having Sex with Men and Blood Donation Blood Collection/Donation Process Obligations to Donors Acknowledgement Further Reading Chapter 23 Blood Donation Testing and the Safety of the Blood Supply Red Cell Serological Testing ABO and D Grouping, and Detection of Red Cell Antibodies High-Titre Anti-A and Anti-B Supplementary Testing Microbiological Testing of Blood Donations and Donor Follow-Up Samples Testing Process and Donor Management Principles of Investigating a Repeat Reactive Sample Principles of Infectious Disease Testing Immunoassays Nucleic Acid Testing Screening Tests and Donor–Recipient Matching Decision Making for Test Implementation Quality Framework and Operational Issues Acknowledgements References Further Reading Chapter 24 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 Platelet Production and Storage Plasma Production and Storage Cryoprecipitate Production and Storage Granulocyte Production and Storage Component Modifications References Further Reading Chapter 25 Blood Transfusion in Hospitals What Does Hospital Transfusion Practice Encompass? Lessons for Hospital Blood Transfusion Practice from Haemovigilance Programmes Key Features of Hospital Transfusion Governance Hospital Transfusion Committees Working Together to Improve the Transfusion Process The Multidisciplinary Hospital Transfusion Team The Role of the Patient and 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 and Feedback 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 Acknowledgement References Further Reading Guidelines and Other Resources Chapter 26 Disaster Preparedness Emergency Preparedness Disasters and Definitions Emergency Planning Organisational Preparation Blood Supply and Donors Clinical Shortage Plans and Transfusion Triage Mass Casualty Events Interoperability Major Incident Response Transfusion Demand Planning Transfusion Risks during Incidents Transfusion Laboratories Business Continuity Concurrency of Events Loss of Utilities and Information and Communications Technology Pandemics Documentation Recovery Phase Staff Support and Welfare Learning from Incidents Acknowledgements References Further Reading Chapter 27 Blood Transfusion in a Global Context Safety and Supply Testing Blood Products Blood Donors Use of Blood Products Systems Improvements Putting the World Health Organization Objectives into Practice in Sub-Saharan Africa Improving the Blood Supply Improving Screening for Blood-Transmitted Infections Meeting the Financial Requirements of Transfusion Services Improving the Clinical Use of Blood: Guidelines for Transfusion Practice Pandemics Conclusion: The Future of Blood Transfusion in a Global Context References Further Reading Chapter 28 Inherited and Acquired Disorders of Haemostasis Normal Haemostasis Investigation of Abnormal Haemostasis Inherited Haemostatic Defects Haemophilia A Haemophilia B Treatment of Patients with Factor VIII or IX Inhibitors Von Willebrand Disease Other Inherited Disorders Acquired Haemostatic Defects Disseminated Intravascular Coagulation Trauma Liver Disease Uraemia Complications of Anticoagulant and Thrombolytic Drugs Cardiopulmonary Bypass Thrombotic Thrombocytopenic Purpura References Further Reading Chapter 29 Point-of-Care Haemostasis Testing Limitations of Conventional Coagulation Testing Point-of-Care Testing Options Viscoelastic Testing Cartridge-Based Technology Use of Point-of-Care Tests in Trauma Adults Children Use of Point-of-Care Tests in Surgical Bleeding Cardiac Surgery Liver Transplant Surgery Other Surgery Populations Supplemental Assays Analysis of Platelet Function Conclusion References Further Reading Chapter 30 Transfusion in Bleeding Patients Volume Loss in Acute Bleeding Platelet Counts Assessment of Coagulation Factors Massive Blood Loss The Acute Coagulopathy of Trauma and Massive Injury Principles of Haemostatic Resuscitation The Limits of Conventional Blood Products Laboratory Support Evidence Can the Lessons of Damage Control Resuscitation for Trauma Be Extended to Other Massive Haemorrhage Situations? Tranexamic Acid Conclusion References Further Reading Chapter 31 Transfusion in Non-Bleeding Medical and Surgical Patients Red Cell Transfusion Thresholds for Red Cell Transfusion Red Cell Transfusion in Critical Illness (see Box 31.1) Perioperative Anaemia Acute Coronary Syndrome Neurological Injury Fresh Frozen Plasma Fresh Frozen Plasma for Bleeding Prophylaxis Fresh Frozen Plasma in Patients with Cirrhosis (see Box 31.2) Conclusion Platelet Transfusion Use of Platelets in the Critically Ill (see Box 31.3) Use of Platelets for Procedural Prophylaxis Harm from Excessive Use of Platelets References Chapter 32 Transfusion in Malignant Haematological Disease Red Cell Transfusions Patients Receiving Intensive Myelosuppressive/Myeloablative Treatment Red Cell Transfusions and Chronic Anaemias Use of Recombinant Erythropoietin in Haematological Disease Platelet Transfusions Indications for Platelet Transfusions Granulocyte Transfusions Approaches to Complications Associated with Blood Transfusion in Patients with Malignant Haematological Disease Transfusion-Transmitted Cytomegalovirus Infection Transfusion-Associated Graft-Versus-Host Disease Human Leucocyte Antigen Alloimmunisation and Refractoriness to Platelet Transfusions Alloimmunisation to Red Cell Antigens ABO-Incompatible Bone Marrow/Peripheral Blood Progenitor Cell Transplants Iron Overload References Further Reading Chapter 33 Transfusion in Benign Haematological Disease Benign Red Blood Cell Disorders Acquired Disorders of Haemolysis Congenital Disorders of Haemolysis Congenital and Acquired Microangiopathic Disorders Benign Platelet Disorders Congenital Disorders of Platelet Function Acquired Disorders of Platelet Function Acquired Immune-Mediated Platelet Disorders Conclusion References Further Reading Chapter 34 Transfusion in Patients with Haemoglobinopathies -Thalassemia -Thalassaemia Red Blood Cell Transfusion in Thalassaemia Sickle Cell Disease Red Blood Cell Transfusion in Sickle Cell Disease Red Blood Cell Transfusion Requirements Complications of Red Blood Cell Transfusion in Haemoglobinopathies Hyperhaemolysis Syndrome Iron Overload Acknowledgement References Further Reading Chapter 35 Transfusing Neonates and Infants Red Blood Cell Transfusion Red Blood Cell Transfusion Thresholds in Infants and Neonates Adverse Outcomes of Anaemia and Transfusion in Neonates Selection of Red Blood Cell Products for Neonates Platelet Transfusion Platelet Transfusion Thresholds in Infants and Neonates Pathogen-Inactivated Platelet and Plasma Transfusion Cellular Product Modifications for Neonates and Infants Non-cellular Plasma Products References Chapter 36 Immunodeficiency and Immunoglobulin Therapy Primary Immunodeficiency Disorders Predominant B-Cell Deficiency Disorders Investigation of Suspected Immunodeficiency Management of Immunodeficiency Immunoglobulin Therapy Immunoglobulin Replacement in Secondary Antibody Deficiency Adverse Effects of Intravenous Immunoglobulin Therapy Risks of Viral Transmission Practical Aspects of Immunoglobulin Therapy: Product Selection and Safe Use Subcutaneous Immunoglobulin References Further Reading Chapter 37 Development of a Patient Blood Management Programme Step 1: Leverage Computerised Physician Order Entry Systems to Guide Evidence-Based Transfusions 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 Chapter 38 Perioperative Patient Blood Management Anaemia and Surgery Blood Transfusion Patient Blood Management in Surgical Practice Preoperative Optimisation Intraoperative Management Postoperative Measures Current Challenges and Future Research in Patient Blood Management Conclusion References Further Reading Chapter 39 Restrictive Transfusion Practice and How to Implement It Level 1 Evidence Supports Restrictive Red Cell Transfusion Practices: Key Clinical Trials Transfusion Triggers and Targets Clinical Practice Guidelines Strategies for Improving Blood Utilisation Clinical Decision Support Improving Blood Utilisation: The Stanford Experience Future Directions Conclusion References Further Reading Chapter 40 Using Data to Support Patient Blood Management 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 Conclusions Conflicts of Interest References Further Reading Chapter 41 Regulation and Accreditation in Cellular Therapy Haematopoietic Stem Cell Transplant Activity The Structure of Stem Cell Transplant Programmes European Union Directives and Legislation International Identifiers: The Single European Code The Human Tissue Act 2004 International Identifiers: GRID Numbers US Food and Drug Administration Non-governmental (Voluntary) Accreditation FACT and JACIE NetCord–FACT AABB College of American Pathologists World Marrow Donor Association Histocompatibility Accreditation Advanced Therapy Medicinal Products Conclusion: How Do Haematopoietic Stem Cell Transplantation Programmes Respond to the Challenge? References Further Reading Chapter 42 Stem Cell Collection and Therapeutic Apheresis Cell Separators Patient Assessment and Treatment Planning Haematopoietic Progenitor Cell Mobilisation Poor Mobilisation: The Use of Plerixafor Peripheral Blood Haematopoietic Progenitor Cell Collection (Leucocytapheresis) Plasma Exchange Red Cell Exchange Extracorporeal Photochemotherapy Apheresis Applications for COVID-19 Patients Complications of Therapeutic Apheresis References Further Reading Chapter 43 Haemopoietic Stem Cell Processing and Storage Background Transplant Procedures Autologous Stem Cell Transplant Allogeneic Stem Cell Transplant Donor Lymphocyte Infusions Haemopoietic Progenitor Cell Products Bone Marrow Peripheral Blood Umbilical Cord Blood Haemopoietic Progenitor Cell Product Assessment and Specialised Procedures Storage of Haemopoietic Progenitor Cell Products Cryopreservation Red Cell Removal Thawing of Cryopreserved Haemopoietic Progenitor Cells Quality Assurance References Further Reading Chapter 44 Haematopoietic Cell Transplantation Principles of Haematopoietic Cell Transplants Indications for Haematopoietic Cell Transplants Source of Haematopoietic Cells Autologous Cells Syngeneic Cells Allogeneic Cells Donor Care and Selection Collecting Haematopoietic Cells Complications of Transplantation Regimen-Related Toxicity Rejection Graft-versus-Host Disease Relapse Infectious Complications Late Effects Bone Marrow Transplant Outcome Post–Bone Marrow Transplant Chimerism and Molecular Monitoring Regulatory Aspects of Haematopoietic Cell Transplantation Conclusion and Future Perspectives References Further Reading Chapter 45 CAR-T Cells and Recent Advances in Clinical Cellular Immunotherapy Cellular Immunotherapy in Haemopoietic Progenitor Cell Transplantation Non-specific T-Cell Immunotherapy The Immune Landscape of Cancer Tumour Antigens Targeting Tumour Antigens with Immunotherapy Chimeric Antigen Receptor T Cells Bispecific T-Cell Engagers and Bispecific Antibodies Tumour-Restricted Natural Killer Cell Immunotherapy Passive Cellular Immunotherapy of Infectious Disease Why Do T-Cell Immunotherapies Fail? Technical Advances Facilitating Translational Research in Cellular Immunotherapy Future Directions References Further Reading Chapter 46 Tissue Banking Regulation Consent Donor Selection and Testing Tissue Procurement Reducing Bacterial Contamination Tissue Processing Supply and Traceability of Tissues Clinical Applications Serious Adverse Events and Reactions Advances in Tissue Processing and Regenerative Medicine Decellularised Tissues Limbal Stem Cells Other Developments Conclusion References Further Reading Chapter 47 Observational and Interventional Trialsin Transfusion Medicine Types of Clinical Studies Observational Studies Randomised Controlled Trials Overall Design Approaches for Randomised Controlled Trials Randomised Controlled Trial Design Alternatives Selecting a Study Population Selecting the Comparator Selecting Outcomes Analysis Conclusion Acknowledgements References Further Reading Chapter 48 Getting the Most Out of the Evidence for Transfusion Medicine and Lessons from the COVID-19 Pandemic What Is Meant by Evidence-Based Medicine? Levels of Clinical Evidence Appraisal of Primary Research Evidence for Its Validity and Usefulness Reviews: Narrative and Systematic Evaluating the Evidence Included in Systematic Reviews Appraisal of Systematic Reviews Comparative Effectiveness Research Evidence Base for Transfusion Medicine Evidence Base for Transfusion Medicine: Individual Examples Conclusion References Chapter 49 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 Multiple Tests of Significance Trial Hypotheses and Common Pitfalls of Interpretation Superiority Trial Equivalence Trial Non-inferiority Trial Meta-analyses and Forest Plots Meta-analyses Forest Plots Emerging Data Science Approaches: Predictive Analysis in Transfusion Medicine Emerging Data Science Approaches: An Introduction to ‘Big Data’ Conclusion References Further Reading Chapter 50 A Primer on Health Economics How Economists Think about the Blood Supply and Transfusions Supply and Demand for Blood Economic Evaluation in Transfusion Medicine Design Model Analysis Conclusion Chapter 51 Scanning the Future of Transfusion Medicine Blood Centre Perspective Business Model Adjustments Real-Time Data Donor and Patient Safety Innovation Hospital Transfusion Service and Patient Care Perspectives Immunohaematological Progress Complications of Transfusion Clinical Transfusion Practice Transfusion Medicine Consultation Alternatives to Transfusion The Future of Cellular Therapy Cellular Therapies That Undergo Minimal Manipulation Cellular Therapies That Undergo More Than Minimal Manipulation The Evolving Role of Transfusion Medicine in Cellular Therapies References Index EULA