Transfusion Medicine and Hemostasis

Clinical and Laboratory Aspects

4th Edition - November 16, 2024
Imprint: Elsevier Science
Editors: Beth H. Shaz, Christopher D. Hillyer, Joseph (Yossi) Schwartz, Morayma Reyes Gil
Language: English
Paperback ISBN:
9 7 8 - 0 - 3 2 3 - 9 6 0 1 4 - 4
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 9 6 0 1 5 - 1

Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects, Fourth Edition continues to be the only "pocket-size" quick reference for pathology and transfusion medicine… Read more

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Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects, Fourth Edition continues to be the only "pocket-size" quick reference for pathology and transfusion medicine for residents and fellows. It is helpful to all physicians and allied health professionals who order and administer blood components, cellular therapies, specialized factors for hemostatic abnormalities, coagulation testing, and those who consult and care for these often very ill patients. This book is ideal for pathology, medicine, surgery, and anesthesia residents, transfusion, hematology, and anesthesia fellows, and certified and specialized practitioners, as well as medical technologist in transfusion, cellular therapy, hematology, and coagulation. This new edition covers the many new developments that have occurred since the previous edition to include new blood products, new indications, or clinical conditions in which blood products are used. Similarly, new hemostasis testing is introduced as well as new clinical scenarios due the COVID-19 pandemic that area relevant to hemostasis and transfusion medicine. This includes COVID coagulopathy, Vaccine Induced Thrombotic Immune Thrombocytopenia, Pediatric reference range in coagulation testing, Platelet rich plasma and MNC products – CAR-T cells.

Title of Book
Cover image
Title page
Table of Contents
Copyright
List of Contributors
About the Editors
Preface
Acknowledgments
Part I. Blood banking and transfusion medicine
Chapter 1. Introduction to Blood Banking and Transfusion Medicine
Blood Transfusion History
Blood Groups
Blood Storage
Blood Derivatives
Blood Component Therapy
Apheresis
Adverse Effects of Transfusion
Donor Safety
Decade of “Right-Sizing” Utilization
Blood Industry
Discipline
Blood Banking
Transfusion Service
National Structure
United States Structure
Chapter 2. Quality Principles in Transfusion Medicine
Basic Principles
Quality Control
Quality Assurance
Quality Management Systems
Association for the Advancement of Blood & Biotherapies
Organization
Resources
Equipment
Supplier and Customer Issues
Process Control
Documents and Records
Deviations, Nonconformances, and Adverse Events
Assessments: Internal and External
Process Improvement
Facilities and Safety
Other Quality Management Systems
The Joint Commission
College of American Pathologists
Clinical and Laboratory Standards Institute
ISO 15,189
Summary
Chapter 3. Regulatory Issues in Transfusion Medicine
Regulation Versus Accreditation
The Food and Drug Administration
Registration and Licensure
Inspections and Compliance Actions
Food and Drug Administration Sanctions
Current Good Manufacturing Practices
Laboratory Laws and Regulations
Other Regulatory Agencies
International Regulation
Chapter 4. Hemovigilance
Origin and Development
Structure and Key Components
Donor Hemovigilance
Recipient Hemovigilance
Vein-to-vein Databases
Advances in Hemovigilance
Future Perspectives
Blood Banking
Chapter 5. Role of the Physician in the Blood Center
Specific Roles
Quality Systems and Laboratories
Risk Management
Clinical and Laboratory Services
Clinical Apheresis
Immunohematology Reference, Platelet, Histocompatibility, and Hematopoietic Progenitor Cell/Tissues Laboratories
Response to Unique Challenges
Research and Development
Education and Training
Donation Process
Chapter 6. The Blood Donor, Donation Process and Technical Aspects of Blood Collection
Blood Donors
The Blood Donor, Donation Process and Technical Aspects of Blood Collection
Recruitment Materials
Educational Materials
Registration
Health Screening
Mini Physical Exam
Donor History Questionnaire
Donor Informed Consent
Technical Aspects
Identification
Venipuncture Site Preparation
Phlebotomy
Postdonation Care
Chapter 7. Apheresis Blood Component Collections
RBC Apheresis Collections
Plateletpheresis Collections
Plasmapheresis Collections
Chapter 8. Recipient Specific Blood Donation
Exceptional Medical Need
Directed Donation
Autologous Donation
Chapter 9. Adverse Donor Reactions
Complications of Whole Blood Donation
Hematoma
Nerve Injury
Vasovagal
Prolonged Recovery
Arterial Puncture
Iron Loss
Complications of Apheresis Donations
Citrate-Induced Hypocalcemia
Machine Malfunction
Allergic Reactions
Lymphocyte Depletion
Granulocytapheresis
Approach to the Donor and Donation Process
Prevention
Predonation Education
Drive Setup and Environment
Selection Criteria
Distraction
Water Ingestion
Applied Muscle Tension
Salty Snacks
Biovigilance and Reporting
Depletion of Iron Stores
Donor and Product Testing
Chapter 10. Serologic Testing of Donor Products
ABO Group Typing
D Antigen Phenotype
Antibody Screening for the Presence of Unexpected RBC Antibodies
Phenotyping RBC Products
Antibody Titer Anti-A, Anti-B
International
Chapter 11. Overview of Infectious Disease Testing
Background
Chapter 12. Human Immunodeficiency Virus Screening
Description
Infection
HIV Types
Determination of Need and Requirement for Testing
Anti-HIV Testing
Nucleic Acid Testing
Automation
Blood Unit Management
Donor Management
For Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)
Chapter 13. Hepatitis B Virus Screening
Determination of Need and Requirement for Testing
HBsAg
Anti-HBc
HBV NAT
Donor Management
For Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)
Chapter 14. Hepatitis C Virus Screening
Determination of Need and Requirement for Testing
Anti-HCV
HCV NAT
Supplemental Testing
Donor Management
For Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)
Chapter 15. West Nile Virus Screening
Determination of Need and Requirement for Testing
NAT Screening
Confirmatory Test
Donor Management
Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)
Chapter 16. Zika Virus Screening
Background
Blood Donor Testing for ZIKV
Donor Screening and Testing for HCT/Ps
Chapter 17. Babesia Screening
Description
Determination of Need and Requirement for Testing
NAT Screening
Antibody Screening
Confirmatory Testing
Blood Unit Management
Donor Management
Chapter 18. Syphilis, Human T-Cell Lymphotropic Virus, and Chagas Screening
Syphilis
Background
Determination of Need and Requirement for Testing
Serologic Screening Tests
Confirmatory/Supplemental Tests
Donor Management
Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)
Human T-Cell Lymphotropic Virus
Background
Determination of Need and Requirement for Testing
Screening Tests
Confirmatory/Supplemental Tests
Donor Management
Human Cells, Tissues, and Cellular and Tissue-Based Products
Chagas Disease
Description
Determination of Need and Requirement for Testing
Screening Test
Confirmatory Tests
Donor Management
Human Cells, Tissues, and Cellular and Tissue-Based Products
Chapter 19. Bacterial Screening
Methods to Minimize Bacterial Contamination
Donor Screening
Skin Preparation
Diversion Pouch
Collection Platform
Methods to Inhibit or Inactivate Bacteria
Cold Storage
Storage Solutions
Pathogen Inactivation
Methods to Detect Contaminated Product
Culture-Based Methods
Immunoassay
Future Considerations
Cellular Therapy Products
Transfusion Medicine
Chapter 20. Role of the Transfusion Service Physician
Specific Roles of the Transfusion Service Physician/Medical Director
Consultative Role for Patient Care
Role in Daily Laboratory Operations
Pretransfusion Testing and Blood Product Selection
Inventory Management
Role in Quality Management for Compliance with Regulatory Agencies
Coordination of a Patient blood Management Program
Hospital Transfusion Committee
Maximum Surgical Blood Order
Informed Consent
Disaster Preparedness and Contingency Plan
Education
Research
Summary
Patient Testing
Chapter 21. Pretransfusion Testing
Patient Identification
Pretransfusion Orders
Type and Screen Request
Request for Transfusion
Patient Specimen
Specimen Storage and Retention
Specimen Age
Pretransfusion Testing
Serologic Testing
Method
Detection Techniques
Automation
Molecular Methods
Recipient Testing
ABO Blood Type
D Type
Antibody Screen
Comparison With Previous Records
Donor Unit Testing
Blood Component Selection
ABO Compatibility
D Compatibility
Other Blood Groups
Crossmatch
Electronic Crossmatch
Immediate Spin Crossmatch
AHG Crossmatch
Labeling and Release of Blood Components
Special Clinical Situations
Neonates
Urgent Requirement for Blood
Quality Assurance
Chapter 22. Antibody Identification
Clinical Significance
Unexpected Antibody Identification
Preanalytical Considerations
Age
Gender
Transfusion History
Race/Ethnicity
Medical History
Drugs
Specimen Requirements
Reagents
Antibody Identification Panel
Antiglobulin Reagent
Testing
Immediate Spin (Room Temperature) Phase
37°C Phase
AHG Phase
Interpretation of Results
How to Read a Panel?
Autologous Control (Autocontrol)
Positive Direct Antiglobulin Test in a Recently Transfused Patient
Phenotyping
Frequency of Testing
Techniques Used in Complex Antibody Identification Cases
Enhancement Media
Enzyme or Chemically Treated RBCs
Prewarm Technique
Cold Antibody Screen
Neutralization
Adsorption
Autologous Adsorption
Allogeneic Adsorption
Immunohematology Reference Laboratory
Determining Clinical Significance of Identified Antibody(ies)
Selection of Blood for Patients With Unexpected Antibody(ies)
Patients Requiring Rare Blood
Chapter 23. Direct Antiglobulin Test
Clinical Indications
Antibody Identification
Autoimmune Hemolytic Anemia
Drug-Induced Immune Hemolytic Anemia
Hemolytic Disease of the Fetus and Newborn
Hemolytic Transfusion Reactions
Testing Methods
Evaluation of a Positive Direct Antiglobulin Test and Additional Testing
Eluate
Panagglutinin
Nonreactive Eluate
Evaluation of a False-Negative Direct Antiglobulin Test
False-Positive Direct Antiglobulin Test
Antigens
Chapter 24. Molecular DNA-Based Blood Group Typing
Genomic Basis of Blood Groups
Source Sample
Approach to the Interpretation of Molecular Blood Group Assays
Testing Methodologies
Real-Time Polymerase Chain Reaction
Bead Technology
Probe Elongation Arrays
DNA Sequencing
Complementary DNA (cDNA) Sequencing
Phenotype-Genotype Discrepancies
Clinical Applications
Recently Transfused Patients
Alloantibody Versus Autoantibody
Hemoglobinopathies and Chronic Transfusion Therapy
Determination of D Status
Transfusion Support for Hematopoietic Stem Cell Transplantation
Drug Interference
Hemolytic Disease of the Fetus and Newborn
Extended Donor Typing and Identification of Rare Donors
Future Perspectives
Chapter 25. ABO & H Blood Group Systems
Antigens
A and B Subgroups
Bombay and Para-Bombay Phenotypes
Antibodies
Antibody Titers
ABO-Incompatible Transplantation
Plasma-Rich Blood Components
ABO-Typing Discrepancies
Genes Encoding H and ABO Antigens
ABO Genotyping
Chapter 26. Rh and RhAG Blood Group Systems
Common Antigens
D Antigen
Weak D
Partial D
C/c and E/e Antigens
G Antigen
V and VS Antigens
Partial Rhce Antigens
Rh-Null
D-Typing Discrepancies
RH Genotyping
Management of RhIG in Pregnancy
Expression
Antibodies
Autoantibodies
Chapter 27. Kell, Kx, and Kidd Blood Group Systems
KEL and Kx Blood Group Systems
Antigens and Their Molecular Basis
McLeod Phenotype
Expression
Antibodies
Kidd Blood Group System
Antigens and Their Molecular Basis
Expression
Antibodies
Chapter 28. MNS and Duffy Blood Group Systems
MNS Blood Group System
Antigens and Genetic Basis
Expression
Antibodies
Duffy Blood Group System
Antigens and Genetic Basis
Expression
Antibodies
Chapter 29. Lewis, I, P1PK, FORS, and GLOB Blood Group Systems
Lewis Blood Group System
Antigens and Genetic Basis
Expression
Antibodies
I Blood Group System
Antigens and Genetic Basis
Expression
Antibodies
Autoantibodies
Alloantibodies
P1PK, Globoside (GLOB), and FORS Blood Group Systems
Antigens and Genetic Basis
Expression
Antibodies
Anti-P1
Anti-PX2
Anti-PP1Pk
FORS Blood Group System
Antigen and Genetic Basis
Antibody
GLOB Collection
Chapter 30. Other Blood Group Systems, Collections, and Antigens
Potentially Clinically Significant Blood Group Systems
LU (ISBT005)
DI (ISBT010)
YT (ISBT011)
SC (ISBT013)
DO (ISBT014)
CO (ISBT015)
GE (ISBT020)
IN (ISBT023)
OK (ISBT024)
GIL (ISBT029)
JR (ISBT032)
LAN (ISBT033)
VEL (ISBT034)
AUG (ISBT036)
PEL (ISBT040)
MAM (ISBT041)
EMM (ISBT042)
ER (ISBT044)
CD36 (ISBT045)
Blood Group Systems Not Considered Clinically Significant
XG (ISBT012)
LW (ISBT016)
CH/RG (ISBT017)
CROM (ISBT021)
KN (ISBT023)
RAPH (ISBT025)
JMH (ISBT026)
CD59 (ISBT035)
SID (ISBT038)
Blood Group Systems of Unknown Clinical Significance
KANNO (ISBT037)
CTL2 (ISBT039)
ABCC1 (ISBT043)
200 (Collections), 700 Series, and 901 Series
Chapter 31. Human Platelet Antigens
Platelet-specific Antigens
Mode of Inheritance
Molecular Basis of Type
Disease Associations
Neonatal Alloimmune Thrombocytopenia
Posttransfusion Purpura
Immune Platelet Refractoriness
Laboratory Diagnosis
Serology
Molecular Techniques for Human Platelet Antigen Typing
Flow Cytometry for HPA Antibody Detection
Solid Phase Techniques for HPA Antibody Detection
Chapter 32. Human Neutrophil Antigens
Nomenclature of HNA Antigens
Disease Associations
Transfusion-Related Acute Lung Injury
Neonatal Alloimmune Neutropenia
Autoimmune Neutropenia
Transfusion-Related Alloimmune Neutropenia
Laboratory Diagnosis
Granulocyte Agglutination Test
Granulocyte Immunofluorescence Test
Monoclonal Antibody Immobilization of granulocyte Antigens Assay
Fluorescent Bead Test
Polymerase Chain Reaction With Sequence-specific Primers
Chapter 33. HLA Antigens
The HLA System
HLA Genes
HLA Antigens
Polymorphism
HLA Typing
DNA Typing Methods
Low Resolution
High Resolution
Allelic Resolution
HLA Nomenclature
Reporting of Ambiguous Typing Results
Anti-HLA Antibodies
HLA and Transplantation
Hematopoietic Stem Cell Transplantation
Number and Direction of Mismatch
Unrelated Adult Volunteer Donors
Unrelated Cord Blood Grafts
Donor Registries
Anti-HLA Antibodies
Solid Organ Transplantation
HLA Matching
Anti-HLA Antibodies
HLA and Transfusion
HLA and Diseases
HLA and Drug Hypersensitivity
Blood Products
Chapter 34. Component Preparation and Manufacturing
Whole Blood
Component Manufacturing
Anticoagulant-Preservative Solutions
RBC Components
Additive Solutions
RBC Modification
Plasma Components
Cryoprecipitate
Cryoprecipitate-Reduced Plasma
Platelet Components
Buffy Coat Platelets
Platelet Modification
Granulocytes
Component Labeling
Chapter 35. Red Blood Cell Products
RBC Storage Lesion
Transfusion Guidelines
Indications
RBC Exchange
Transfusion Trigger
Guidelines
Restrictive Versus Liberal Transfusion Strategies
Special RBC Products and Circumstances
Administration
ABO/D Compatibility
Quality Assurance
Dose
Adverse Events
Alternatives and Future Considerations
International Considerations
Chapter 36. Plasma Products
Product Names
Description
Plasma Products
FFP, FP24, PF24RT24, and Thawed Plasma
CRP
S/D Plasma
PR Plasma
Liquid Plasma
Recovered and Source Plasma (Plasma for Manufacture)
Indications
Liver Disease
Massive Transfusion
Rapid Warfarin Reversal
Disseminated Intravascular Coagulation
Plasma Exchange Replacement Fluid
Congenital Coagulation Factor Deficiencies
Other Multiple Coagulation Defects
Prophylactic Use
Dosage
Compatibility
Adverse Events
Alternatives to Plasma Products
Chapter 37. Platelet Products
Product Names
Description
Indications
Relative Contraindications
Platelet Products and Their Modifications
Whole Blood–Derived Platelets
Apheresis
Buffy Coat–Prepared Platelets
Storage
Bacterial Testing
Pathogen-Reduced Versus Standard Platelets
Leukoreduction
Irradiation
Washing or Volume Reduction
Aliquots
Quality Control
Dose
Product Selection
ABO Compatibility
D Compatibility
Adverse Events
Chapter 38. Cryoprecipitate and Fibrinogen Concentrates
Products
Description
Indications
Acquired Hypofibrinogenemia
Massive Transfusion
Fibrin Glue/Sealant
Factor XIII Deficiency
Bleeding Complications after Thrombolytic Therapy
Uremic Bleeding
Processing and Storage
Preparation and Administration
ABO/D Compatibility
Thawing and Pooling
Expiration
Quality Assurance
Dose
Fibrinogen Replacement
Factor XIII Replacement
Adverse Events
International Standards
Chapter 39. Granulocyte Products
Indications
Neonatal Sepsis
Neutrophil Function Defects
Neutropenia and Sepsis
Collection
Storage
Patient Selection
Dose
Preparation
Administration
Toxicities
Quality Assurance
International Issues
Chapter 40. Albumin and Related Products
Albumin
Indications
Therapeutic Plasma Exchange
Ovarian Hyperstimulation Syndrome
Cirrhosis With Spontaneous Bacterial Peritonitis
Large-Volume Paracentesis
Hepatorenal Syndrome Type 1
Nephrotic Syndrome
Sepsis
Burns
Contraindications
Adverse Effects
Cost and Usage
Manufacturing
Storage
Preparation and Administration
Dosing
Adult
Pediatric
Other Colloid Solutions
Plasma Protein Fraction
Dextrans
Gelatins
Hydroxyethyl Starch
Chapter 41. Human Immune Globulin Preparations
Description
Mechanism of Action
Indications and Dose
Preparation and Administration
Production
Plasma Collection
Processing
Selecting a Product
Administration
Adverse Events
Anaphylactic Reactions
Aseptic Meningitis
Hemolytic Transfusion Reactions
Infectious Disease Transmission
Passively Acquired Antibodies
Renal Failure
Thromboembolic Events
Transfusion-Related Acute Lung Injury
Chapter 42. Hyperimmune Products
Description
Pathophysiology
Preparation and Administration
Infection-Associated Hyper-Ig Products
Non-Infection-Associated Hyper-Ig Products
Adverse Events
Chapter 43. Rh Immune Globulin
Preparation and Administration
Indications to Prevent Anti-D Formation
Perinatal Administration
D-Positive Blood Product Transfusion Into D-Negative Recipients
Indications for Use in Immune Thrombocytopenia
Adverse Reactions
International Standards
Chapter 44. Coagulation Factor Products
Coagulation Factor Concentrate Production
Coagulation Factor Therapy Monitoring
Coagulation Factor Concentrate Dosing
Chapter 45. Autologous Platelet Gel
Manufacturing
Application
Mechanism of Action
Indications
Hemostasis
Wound Sealing
Bone Graft Coalescence and Osteogenesis
Contraindications
Limitations
Chapter 46. Convalescent Plasma
Mechanism of Action
Modes of Deployment and Use in US During COVID-19 Pandemic
Summary of Clinical Evidence of CCP Use
AABB Guidelines for CCP Use
Summary
Chapter 47. Pharmacologic Approaches to Bleeding
Antifibrinolytic Agents
Lysine Analogs
Aprotinin
Protamine
Desmopressin
Recombinant Coagulation Products and Purified Factor Concentrates
Recombinant Activated Factor VIIa
Prothrombin Complex Concentrates
Chapter 48. Blood Pharming and Alternative Blood Products
Donor Dependency Risks in the Future Blood Supply
Synthetic Blood Alternatives to Substitute Blood Cells
Red blood Cells
Platelets
Manufacturing Mature Blood Cells From Stem Cells
Directed Differentiation of iPSCs Toward Mature Blood Cells
Current Challenges with iPSC-Derived RBCs
Current Challenges with iPSC-Derived Platelets
Humanized Xenogeneic Blood Production
Product Modifications
Chapter 49. Irradiation of Blood Products
Indications
Guidelines and Standards for Irradiation and Mitigation of TA-GVHD
Universal Irradiation
Blood Products Requiring Irradiation
Processing and Storage
Sources of Irradiation
Dose
Quality Assurance
Storage and Expiration
Adverse Events
International Considerations
Chapter 50. Leukoreduction of Blood Products
Definitive Indications
Decreasing Incidence of Febrile Nonhemolytic Transfusion Reactions
Decreasing Incidence of HLA Alloimmunization
Decreasing Cytomegalovirus Transmission
Potential Indications
Decreasing Other Human Herpesvirus Transfusion-Transmitted Infections
Prion Disease
Reduction in the Risk of Transfusion-Associated Graft Versus Host Disease
Controversial Indication
Transfusion-Related Immunomodulation
Contraindication
Quality Assurance
In-Lab Versus Bedside Leukoreduction
International Differences
Chapter 51. CMV- Safe Products
Description
Indications
Processing and Storage
CMV-Safe by Leukoreduction of Cellular Blood Components
CMV-Safe by Pathogen Reduction
CMV Screening of Donors
Practice Guidelines
Quality Assurance
International Practices
Chapter 52. Frozen Blood Products
Cryopreserved RBC Products
Indications
Cryopreservation with Glycerol
Rejuvenation
Thawing and Deglycerolization
Cryopreserved Platelets Products (CPP)
Chapter 53. Washed Blood Products
Washed RBC Products
Washed Platelet Products
Possible Indications (Table 53.1)
Prevention of Severe Allergic/Anaphylactic Transfusion Reactions
Other Transfusion Reactions
ABO Out-of-Group Transfusion
Large Volume or Rapid Transfusion into Neonates and Small Children
Cardiopulmonary Bypass
Fetal and Neonatal Alloimmune Thrombocytopenia
Paroxysmal Nocturnal Hemoglobinuria
Extracellular Vesicles
Chapter 54. Volume-Reduced Blood Products
RBC Products
Methods
Indications
Adverse Effects
Platelet Products
Methods
Indications
ABO Out-of-Group Platelet Transfusion
Prevention of Transfusion-Associated Cardiovascular Overload
Decrease in Febrile Nonhemolytic Transfusion Reactions
Adverse Effects
Hematopoietic Progenitor Cell Products
Chapter 55. Pathogen Reduction Technologies
Pathogen Reduction Technologies
Solvent/Detergent (S/D)
THERAFLEX Methylene Blue
THERAFLEX UV-C
Mirasol (Riboflavin/UV Light)
INTERCEPT (Amotosalen/UVA)
INTERCEPT (Amustaline/Glutathione)
PR Blood Components
Plasma
Platelets
Whole Blood/Red Blood Cells
Summary
Specific Clinical Settings
Chapter 56. Neonatal and Pediatric Transfusion Medicine
Red Blood Cell Transfusions
RBC Transfusion Considerations in Neonates
RBC Product Selection for Neonates
Leukoreduction
Cytomegalovirus-Seronegative
Irradiation
Neonatal RBC Compatibility Testing
Neonatal RBC Exchange Transfusion Considerations
RBC Transfusions in Children and Adolescents
RBC Product Selection in Children and Adolescents
Platelet Transfusions
Platelet Transfusions in Neonates
Platelet Transfusions in Children
Platelet Product Selection
ABO/RhD Compatibility
Leukoreduction
Cytomegalovirus-Seronegative
Irradiation
Washing or Volume Reducing
Pathogen Inactivation
Plasma Transfusions
Plasma Product Selection
Cryoprecipitate Transfusions
Cryoprecipitate Product Selection
Granulocyte Transfusions
Granulocyte Product Selection
Chapter 57. Perinatal Transfusion Medicine and Hemolytic Disease of the Fetus and Newborn
Hemolytic Disease of the Fetus and Newborn
Prevention of HDFN
Prenatal and Neonatal Transfusion Testing
Determining D Type for RhIg Prophylaxis Eligibility
RhIg Prophylaxis
Fetomaternal Hemorrhage Testing
Rosette Test (Fetal RBC Screen [Qualitative])
Kleihauer–Betke Test (Fetal RBC Count [Quantitative])
Flow Cytometry (Fetal RBC Count [Quantitative])
RhIg Dosing in the Presence of Fetomaternal Hemorrhage
Other Strategies for the Prevention of HDFN
Testing for the Detection of HDFN
Alloantibodies Currently or Previously Detected
Phenotype the Father
Antibody Titration
Middle Cerebral Artery Peak Systolic Velocity
Amniocentesis
Periumbilical Cord Blood Sampling
Perinatal Transfusion Management of HDFN
Intrauterine RBC Transfusions
RBC Product Selection
Postnatal Management of HDFN
Neonatal Testing
Treatment of the Neonate with HDFN
RBC Exchange Transfusion
Chapter 58. Autoimmune Hemolytic Anemias
Clinical Presentation and Predictors of Outcome
Warm Autoimmune Hemolytic Anemia
Pathogenesis
Treatment
Transfusion Management
Direct Antiglobulin Test Negative Autoimmune Hemolytic Anemia
Alternative Testing Techniques
Cold Agglutinin Hemolytic Anemia
Pathogenesis
Treatment
Transfusion Management
Mixed AIHA
Paroxysmal Cold Hemoglobinuria
Pathogenesis
Treatment
Transfusion Management
Drug-Induced Immune Hemolytic Anemia
Drug Adsorption (Hapten) Hypothesis
Immune Complex Hypothesis
Autoantibody Induction by Drugs
Nonimmunologic Protein Adsorption (Membrane Modification)
Transfusion Management
Summary
Chapter 59. Transfusion Management of Patients With Sickle Cell Disease and Thalassemia
Sickle Cell Disease
Pathophysiology
RBC Transfusion
RBC Product Selection
Antigen Matched
Risks of Transfusion
Alloantibody Formation
Autoantibody Formation
Infection
Iron Overload
Hyperhemolytic Transfusion Reaction
Thalassemia
Pathophysiology
β-Thalassemia
α-Thalassemia
RBC Transfusion
Risks of Transfusion
Alloantibody and Autoantibody Formation
Transfusion Reactions
Iron Overload
Chapter 60. Transfusion Management of Patients Undergoing Hematopoietic Stem Cell
Product Selection
Leukoreduction
Cytomegalovirus Safe
Irradiation
ABO/RhD Compatibility
Red Blood Cell Transfusion
Platelet Transfusion
Plasma Transfusion
Granulocyte Transfusion
Special Considerations Based on Donor/Recipient ABO Mismatch
Chapter 61. Transfusion of Patients Undergoing Solid Organ Transplantation
Product Selection
Leukoreduction
Irradiation
ABO/RhD Compatibility
Special Considerations Based on Donor/Recipient ABO Incompatibility
RBC Transfusion
Platelet Transfusion
Plasma Transfusion
Other Considerations
Chapter 62. Transfusion Support and Hemostatic Monitoring in Patients Connected to Extracorporeal Membrane Oxygenation-Related Devices
Cardiopulmonary Bypass
Extracorporeal Life Support
Anticoagulation in Extracorporeal Circuits
Cardiopulmonary Bypass
Extracorporeal Life Support
Transfusion Support and ECLS
Chapter 63. Transfusion Management of Patients Receiving Antithrombotic Therapy
Venous Thrombosis Prophylaxis
Warfarin
Heparins
Direct Xa Inhibitors
Direct Thrombin Inhibitors
Arterial Thrombosis Prophylaxis
Aspirin
Adenosine Diphosphate (ADP) Receptor Inhibitors
Protease-Activated Receptor 1 (PAR-1)Inhibitors
GPIIb/IIIa Inhibitors
Lab-Guided Platelet Transfusion
Chapter 64. Blood Transfusion in Low-Resource Settings
Provision of Blood for Transfusion
Blood Systems and Financing
Blood Supply
Blood Donors
Blood Screening for Transfusion-Transmissible Infections
Blood Processing
Hospital Management of Blood and Blood Transfusions
Hospital Transfusion Procedures
Clinical Use of Blood
Hospital Transfusion Committees
Hemovigilance
Regulation and Accreditation
Addressing Transfusion Challenges
WHO Action Framework
Transfusion Medicine Research
Chapter 65. Management of Patients Who Decline Blood Transfusion
Introduction
Patient Approach
Perioperative Management
Intraoperative Management
Critical Anemia Management
Blood Substitutes
Summary
Chapter 66. Platelet Transfusion Refractory Patients
Calculation of Refractoriness
Nonimmune Refractoriness
Immune Refractoriness
Laboratory Testing for Immune-Mediated Platelet Transfusion Refractoriness
Human Leukocyte Antigen Antibody Detection
Human Glycoprotein Platelet Antigen Antibody Detection
Platelet Transfusion Support for the Human Leukocyte Antigen Alloimmunized Patient
Human Leukocyte Antigen-Matched Platelets
Crossmatched Platelets
Human Leukocyte Antigen Antibody-Specific Prediction
Bleeding, Platelet Refractory Patients
Summary
Chapter 67. Massive Transfusion
Massive Transfusion in Trauma
Coagulopathy of Trauma
Hemostatic Resuscitation in Trauma
Massive Transfusion in Nontrauma-Related Hemorrhage
Component Therapy During Massive Transfusion
Red Blood Cells
Plasma, Platelets, and Cryoprecipitate
Whole Blood
Massive Transfusion Protocols
Pharmacologic Agents
Chapter 68. Patient Blood Management
Implementing a Hospital-Wide Blood Management Program
National Trends in Blood Utilization: Objective Nationwide Evidence of PBM Effectiveness
Key Tenets in Patient Blood Management (Table 68.1)
Minimizing Inappropriate Blood Use Through Evidence-Based Guidelines
Minimizing Phlebotomy-Related Blood Loss
Treating Preoperative Anemia and Coagulopathy
Autologous Blood Conservation
Preoperative Autologous Donation
Acute Normovolemic Hemodilution
Intraoperative Blood Recovery
Postoperative Blood Recovery
Adverse Events
Minimizing Perioperative Blood Loss
Drugs
Topical Hemostatic Agents
Operative Techniques
Adequate Postoperative Management
Summary
Transfusion Adverse Events
Chapter 69. Overview of Adverse Events and Outcomes after Transfusion
Serious Hazards of Transfusion
Leading Causes of Transfusion-Associated Death
Transfusion-Related Acute Lung Injury
Transfusion-Associated Circulatory Overload
Hemolytic Transfusion Reaction and Mistransfusion
Developing Noninfectious Serious Hazards of Transfusion
Transfusion-Associated Morbidity and Mortality
Hemovigilance Systems
Chapter 70. Febrile Nonhemolytic Transfusion Reactions
Clinical Presentation
Diagnosis
Incidence
Platelets
Red Blood Cells
Plasma
Pathophysiology
Treatment
Prevention
Chapter 71. Allergic Transfusion Reactions
Incidence
Clinical Manifestations
Pathophysiology
IgA Deficiency and Anti-IgA
Diagnosis
Differential Diagnosis
Management
Mild Allergic Transfusion Reactions
Severe Allergic Transfusion Reactions
Prevention
Prophylactic Premedication
Chapter 72. Acute Hemolytic Transfusion Reactions
Incidence
Transfusion of ABO-Incompatible RBCs
Transfusion of Non-ABO-Incompatible RBCs to Alloimmunized Recipients
Transfusion of Significant Amounts of Incompatible Plasma
Clinical Manifestations, Diagnosis, and Evaluation
Transfusion Service Evaluation
Other Causes of Acute Hemolysis
Pathophysiology
Intravascular Hemolysis
Clinical Sequelae
Management
Prevention
Chapter 73. Delayed Hemolytic Transfusion Reactions
Incidence
Clinical Manifestations
Pathophysiology
Diagnosis
Differential Diagnosis
Management
Prevention
Hyperhemolytic Transfusion Reaction
Chapter 74. Transfusion-Associated Circulatory Overload
Incidence
Clinical Manifestations
Pathophysiology
Diagnosis
Differential Diagnosis
Management
Prevention
Summary
Chapter 75. Transfusion-Related Acute Lung Injury
Incidence
Clinical Manifestations
Pathophysiology
Diagnosis
Differential Diagnosis
Management
Donor/Recipient Investigation
Prevention
Summary
Chapter 76. Septic Transfusion Reactions
Clinical Presentation
Management
Incidence and Implicated Bacteria
RBC Products
Platelets (Apheresis and Whole Blood–Derived) Products
Plasma and Cryoprecipitate Products
Mitigation Strategies
RBC Products
Platelet Products
Summary
Chapter 77. Transfusion-Associated Dyspnea, Hypotensive Reactions, Metabolic and Other Acute Complications of Transfusion
Transfusion-Associated Dyspnea
Clinical Features
Diagnosis
Treatment
Hypotensive Transfusion Reactions
Pathophysiology
Clinical Features
Diagnosis
Treatment
Prevention
Metabolic Complications of Transfusion
Pathophysiology
Hyperkalemia and Hypokalemia
Hypothermia
Hypocalcemia
Hypomagnesemia
Clinical Features
Diagnosis
Treatment
Prevention
Chapter 78. Posttransfusion Purpura
Pathophysiology
Clinical Manifestations
Diagnosis
Treatment
Prevention
Chapter 79. Transfusion-Associated Graft-Versus-Host Disease
Normal Clearance of Transfused Lymphocytes
Pathophysiology
Clinical Manifestations
Diagnosis
Treatment
Prevention
Blood Product Factors
Age of Blood
Patients at Increased Risk
Congenital Immunodeficiency Patients
Allogeneic and Autologous Hematopoietic Progenitor Cell Recipients
Hematologic Malignancies
Recipients of Fludarabine, Other Purine Analogs and Drugs/Antibodies That Affect T-Lymphocyte Number or Function
Fetuses and Neonates
Aplastic Anemia
Patients Receiving Chemotherapy and Immunotherapy
Solid Organ Transplantation Recipients
Human Immunodeficiency Virus and Acquired Immune Deficiency Syndrome Patients
Cardiovascular Surgery
Immunocompetent Patients
Transfusion-Associated Microchimerism
Chapter 80. Transfusion-Related Immunomodulation
Accepted Transfusion-Related Immunomodulation Effects
Solid Organ Transplantation
Decreased Likelihood of Recurrent Spontaneous Abortions
Debated Transfusion-Related Immunomodulation Effects
Cancer, Infection, and Autoimmunity
Proposed Mechanisms of Transfusion-Related Immunomodulation
Traditional TRIM
Recent TRIM
Potential Problems With Transfusion-Related Immunomodulation Science
Chapter 81. Iron Overload
Pathophysiology
Clinical Manifestations
Diagnosis
Management
Chapter 82. Transfusion-Transmitted Diseases
General Mitigation Strategies
Retroviruses
Human Immunodeficiency Virus
Risk of Transfusion-Transmission
Human T-Lymphotropic Viruses 1 and 2 (Primate T-Lymphotropic Virus-1/2)
Risk of Transfusion-Transmission
Hepatitis Viruses
Hepatitis C Virus
Risk of Transfusion-Transmission
Hepatitis B Virus
Acute Infections
Chronic Infections
Risk of Transfusion-Transmission
Hepatitis A Virus
Risk of Transfusion Transmission
Hepatitis E Virus
Risk of Transfusion Transmission
Herpes Viruses
Cytomegalovirus
Risk of Transfusion Transmission
Epstein–Barr Virus
Human Herpes Virus 8
Parvovirus B19
Risk of Transfusion-Transmission
Arboviruses
West Nile Virus
Risk of Transfusion-Transmission
Dengue Virus
Risk of Transfusion-Transmission
Chikungunya Virus
Risk of Transfusion-Transmission
Zika Virus
Risk of Transfusion-Transmission
Powassan Virus
Atypical Bacteria
Anaplasma Phagocytophilum
Risk of Transfusion Transmission
Protozoa
Plasmodium spp. (Malaria)
Risk of Transfusion-Transmission
Trypanosoma Cruzi
Risk of Transfusion-Transmission
Babesia
Risk of Transfusion-Transmission
Toxoplasma Gondii
Leishmania
Prions
Transmissible Spongiform Encephalopathies
Ensuring Responsiveness to Future Emerging
Therapeutic Apheresis and Phlebotomy
Chapter 83. Overview of Therapeutic Apheresis
Principle
Methods
Vascular Access
Volume to Exchange and Frequency of TA Procedures
Calculations
Replacement Solutions
Anticoagulation
Citrate
Heparin
Adverse Events
Allergic Reactions
Citrate Toxicity
Hypotension
ACE Inhibitor Reactions
Evaluation of a New Patient for Therapeutic Apheresis Initiation
Chapter 84. Therapeutic Plasma Exchange
Pathophysiology
Volume Exchanged
Replacement Fluid
Drug Removal During Apheresis
The American Society for Apheresis (ASFA) Guidelines
Category I Indications for TPE (ASFA Guidelines, 2023)
Acute Inflammatory Demyelinating Polyradiculoneuropathy
Antiglomerular Basement Membrane Disease with Diffuse Alveolar Hemorrhage (DAH) or Dialysis-independence (Dialysis-dependence, No DAH Is a Category III)
Catastrophic Antiphospholipid Syndrome (CAPS)
Chronic Acquired Demyelinating Polyneuropathies, IgG/IgA/IgM Related
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Focal Segmental Glomerulosclerosis (FSGS) Recurrent in Kidney Transplant (Steroid Resistant in Native Kidney Is Category III)
Hyperviscosity in Hypergammaglobulinemia (Symptomatic or Prophylaxis for Rituximab)
Myasthenia Gravis, Acute Short-term treatment (Long-term treatment Is Category II)
N-methyl-d-aspartate Receptor Antibody Encephalitis
Thrombotic Microangiopathy, Complement-mediated, Factor H Autoantibody (Complement Factor Gene Mutations Is Category III)
Thrombotic Microangiopathy, Drug Induced, Ticlopidine (Clopidogrel Is Category III, Gemcitabine/Quinine Is Category IV)
Thrombotic Microangiopathy, Thrombotic Thrombocytopenic Purpura (TTP)
Transplantation, Kidney, ABO Compatible, Antibody Mediated Rejection or Desensitization/Prophylaxis, Living Donor
Transplantation, Kidney, ABO Incompatible Desensitization, Living Donor (Antibody Mediated Rejection Is Category II)
Transplantation, Liver, Desensitization, ABO Incompatible Living Donor (Desensitization, ABO Incompatible Deceased Donor/Antibody Mediated Rejection Is Category III)
Wilson Disease, Fulminant
Category II Indications for TPE (ASFA Guidelines, 2023)
Acute Disseminated Encephalomyelitis, Steroid Refractory
Acute Toxins, Venoms and Poisons, Mushroom Poisoning (Envenomation, Other Are Category III)
Autoimmune Hemolytic Anemia, Severe Cold Agglutinin Disease (Severe Warm Autoimmune Is a Category III)
Cryoglobulinemia, Severe/symptomatic
Erythropoietic Protoporphyria (EPP), Liver Disease
Familial Hypercholesterolemia
Lambert–Eaton Myasthenic Syndrome
Multiple Sclerosis, Acute Attack/Relapse (Chronic Is Category III)
Myasthenia Gravis, Long-term treatment (Acute, Short-term treatment Is Category I)
Myeloma Cast Nephropathy
Neuromyelitis Optica Spectrum Disorder, Acute Attack/Relapse (Maintenance Is Category III)
Pediatric Autoimmune Neuropsychiatric Disorders, PANDAS/PANS Exacerbation (Sydenham's Chorea, Severe Is Category III)
Phytanic Acid Storage Disease
Steroid-Responsive Encephalopathy Associated with Autoimmune Thyroiditis (SREAT)
Systemic Lupus Erythematosus, Severe
Thyroid Storm
Transplantation, Heart, Desensitization/Rejection Prophylaxis (Antibody Mediated Rejection Is Category III)
Transplantation, Hematopoietic Stem Cell, ABO Incompatible (Different Subsets of this Disease Are Category II or III, Refer to ASFA Guidelines for Complete Delineations)
Transplantation, Kidney, ABO Incompatible, Antibody Mediated Rejection (Desensitization, Living Donor Is Category I)
Vasculitis, Hepatitis B Polyarteritis Nodosa (Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Are Category III)
Voltage-Gated Potassium Channel Antibody-mediated Diseases
Chapter 85. Therapeutic Erythrocytapheresis
Exchange Volume
Replacement Fluid
Adverse Events
Indications for ET and RBCx (First Line Therapeutics in Accordance with the American Society for Apheresis (ASFA) Guidelines)
Hereditary Hemochromatosis
Polycythemia Vera and Erythrocytosis
Sickle Cell Disease
Chapter 86. Therapeutic Thrombocytapheresis
Method
Volume Exchanged
Replacement Fluid
Anticoagulant
Frequency
Indications
Thrombocytosis
Chapter 87. Therapeutic Leukocytapheresis and Adsorptive Cytapheresis
Adsorptive Cytapheresis Devices
Processing Volume
Replacement Fluid
Indications: (First or Second Line Therapeutics in Accordance with the American Society for Apheresis (ASFA) Guidelines)
Hyperleukocytosis
Behçet's Disease (BD)
Other Indications
Chapter 88. Extracorporeal Photopheresis
Extracorporeal Photopheresis Principles
Methods
Anticoagulant
Adverse Effects
Indications
Cardiac Allograft Rejection (for Prophylaxis or Treatment of Rejection)
Cutaneous T-Cell Lymphoma (Erythrodermic Mycosis Fungoides and Sézary Syndrome)
Graft-Versus-Host Disease (for Acute or Chronic GVHD)
Lung Allograft Rejection
Chapter 89. LDL Apheresis
Anticoagulant
Adverse Events and Contraindications
Indications
Familial Hypercholesterolemia
Focal Segmental Glomerulosclerosis (FSGS) Refractory to Standard Therapies
Peripheral Vascular Disease (PVD)
Refsum's Disease
Sudden Sensorineural Hearing Loss
Chapter 90. Immunoadsorption
Protein A Immunoadsorption
Adverse Effects
Indications
Cryoglobulinemia
Dilated Cardiomyopathy With New York Heart Association (NYHA) II–IV
Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders
Paraneoplastic Neurologic Syndromes
Paraproteinemic Polyneuropathies Caused by IgG, IgA, or IgM
Renal Transplant
Chapter 91. Therapeutic Phlebotomy
Indications
Hereditary Hemochromatosis
Secondary Iron Overload
Polycythemia Vera
Secondary Erythrocytosis
Recommended Approach
Adverse Events
Cellular Therapy, Regenerative Medicine, and Tissue Banking
Chapter 92. Overview of Cellular Therapy
Donors
Sources of Cells
Stem Cells
Hematopoietic Progenitor Cell Products
Human Embryonic Stem Cells (hESC)
Induced Pluripotent Stem Cells (iPSC)
Mesenchymal Stromal Cells
Differentiated Cells
Immunomodulatory Cells
Adoptive Cell Transfer
Release Testing
Development of New Cellular Therapies
Chapter 93. Hematopoietic Progenitor Cell Products Derived From Bone Marrow and Peripheral Blood
Hematopoietic Stem Cell Transplantation
Hematopoietic Progenitor Cell Products
HPC, Marrow
HPC, Apheresis
HPC, Marrow versus HPC, Apheresis
Processing HPC Products
Plasma and RBC Reduction
Positive and Negative Cell Selection
Purity and Potency
Cryopreservation and Storage
Thawing, Infusion, and Adverse Events
Chapter 94. Cord Blood Banking
Cord Blood as a Hematopoietic Stem Cell Source for Unrelated Transplantation
Advantages
Considerations
Types of Cord Blood Banking
Recommendations
Public Cord Blood Banking
Collection
Processing
Cryopreservation
Storage
Testing
Potency Evaluation
Bacteriology
Infectious Disease Markers
Identity Testing
Hemoglobinopathy Screening
Search Inventory
Cord Blood Unit Release for Clinical Transplantation
Transportation to the Transplant Centers
Thawing and Preparation for Infusion
National Cord Blood Inventory
Oversight and Regulatory Aspects of Public Cord Blood Banking
Food and Drug Administration
Current Good Manufacturing Practices
NETCORD-FACT and AABB
Unrelated Cord Blood Grafts in Clinical Transplantation
Ex Vivo Expansion of Cord Blood Hematopoietic Progenitor Cells to Improve Engraftment
Cord Blood in Regenerative Medicine
Chapter 95. Hematopoietic Progenitor Cell and Mononuclear Cell Collections
Hematopoietic Progenitor Cell Collections
Hematopoietic Progenitor Cell Mobilization
Hematopoietic Progenitor Cell Apheresis Collection
Mononuclear Cell Collections
Chapter 96. Regenerative Medicine
Definitions
Stem Cell
Embryonic Stem Cells
Induced Pluripotent Stem Cells
Regenerative Approaches to Retinal Disease
Stem Cell Approaches to Inherited Retinal Diseases
Human Retinal Progenitors
Pluripotent Cell-Derived Retinal Pigment Epithelial Cells
HESC-RPE in Suspension
HESC-RPE Suspensions Directed Specifically Over Areas on Geographic Atrophy
HESC-RPE on a Membrane
Autologous iPSC-RPE in Suspension
Autologous iPSC-RPE on a Membrane
Summary
Chapter 97. T Cell and Related Immunotherapies
Engineered, Redirected T Cells
Tumor-Infiltrating Lymphocytes
Antiviral Cellular Therapy and Prophylaxis
Transfusion Medicine Interface with Cellular Immunotherapies
Chapter 98. Gene Therapy
Historical Milestones in Gene Therapy
Considerations for Gene Therapy Development and Application
Systemic or Local Effect
Direct or Cell-Based Delivery
Nonviral or Viral Vectors
Gene Addition or Editing
Recent Clinical Advances
Chapter 99. Adverse Events Associated with HPC Products
Incidence
Common Symptoms
Nausea and Vomiting
Fever and Chills
Hypertension and hypotension
Bradycardia
Chest Tightness and Shortest of Breath
Hemoglobinuria
Neurological Symptoms
Nonimmunologic Reactions
DMSO Toxicity
Hemolysis and Aggregate Formation Toxicities
Circulatory Overload
Bacterial Contamination and Septic Reaction
Immunologic Reactions
Major ABO Incompatibility
Minor ABO Incompatibility
Passenger Lymphocyte Syndrome
Allergic Reactions
Transfusion Related Acute Lung Injury
Febrile Nonhemolytic Transfusion Reaction
Activated T Cells
Graft Versus Host Disease
Strategies for Reduction and Prevention of Adverse Reactions
Reporting and Investigation
Chapter 100. Regulatory and Quality Issues in Cellular Therapy
Accreditation Standards
Foundation for the Accreditation of Cellular Therapy
Association for the Advancement of Blood and Biotherapies
College of American Pathologists
Regulatory Standards
The Clinical Laboratory Improvement Amendments
Investigational New Drug
Current Good X Practice
Donor Eligibility
Quality Program
Personnel
Procedures
Facilities
Equipment
Supplies and Reagents
Recovery
Processing and Process Controls
Process Changes and Validation
Labeling
Storage
Receipt and Distribution
Records
Complaint File
Licensure
HPC, Cord Blood
Future
Chapter 101. Tissue Banking in the Hospital Setting
Tissue Types
Regulatory Oversight
Tissue Recovery
Hospital Tissue Services
Decentralized Tissue Services
Centralized Tissue Services
Part II. Hemostasis
Chapter 102. Overview of the Coagulation System
Primary Hemostasis
Platelet Adhesion
Platelet Activation
Platelet Secretion
Microparticle Secretion
Platelet Aggregation
Secondary Hemostasis
Role of Endothelial Cells in Regulating Coagulation
Tertiary Hemostasis: Fibrinolysis
Clinical Coagulation
Chapter 103. Approach to the Bleeding Child
Basic Considerations for Evaluation of a Pediatric Patient With a Bleeding Disorder
Am I Dealing With Bleeding Disorder?
Is Bleeding Congenital or Acquired?
Am I Dealing With Defect in Primary Hemostasis or Secondary Hemostasis?
Laboratory Evaluation
Clinical Testing for Evaluating Primary Hemostasis
Platelet Function Assay (PFA-100)
Clinical Assays for Evaluating Secondary Hemostasis
Global Coagulation Assays
Limitations to the Current Laboratory Assays
Neonatal Thrmbocytopenia
Chapter 104. Congenital Thrombocytopenia
Diagnosis
Differential Diagnosis
Management
Congenital Thrombocytopenias
Disorders With Small Platelets (Microthrombocytopenia)
Wiskott–Aldrich Syndrome and X-Linked Thrombocytopenia
Congenital Autosomal Recessive Microthrombocytopenia Associated with FYB Mutations
Disorders with Normal-Sized Platelets (Normocytic Thrombocytopenia)
Congenital Amegakaryocytic Thrombocytopenia
Amegakaryocytic Thrombocytopenia with Radio/Ulnar Synostosis
Thrombocytopenia Absent Radii
Familial Platelet Disorder with Predisposition to Acute Myelogenous Leukemia
Familial Thrombocytopenia Two or ANKRD26-Related Thrombocytopenia
ETV6-Associated Thrombocytopenia with Predisposition to Acute Lymphoblastic Leukemia
Paris-Trousseau/Jacobsen Syndrome
Disorders with Large Platelets (Macrothrombocytopenia)
Bernard–Soulier Syndrome, 22q11.2 Deletion Syndrome, Mediterranean Macrothrombocytopenia, and Platelet-Type von Willebrand Disease
MYH9-Related Diseases
Autosomal Dominant Macrothrombocytopenia Associated with Hearing Loss
Gray Platelet Syndrome
GATA-1-Related Thrombocytopenia
Other Macrothrombocytopenias
Chapter 105. Fetal and Neonatal Alloimmune Thrombocytopenia
Pathophysiology
Clinical Presentation
Diagnosis
Differential Diagnosis
Management
Antenatal
Screening
Prophylaxis
Chapter 106. Acquired Neonatal Thrombocytopenia
Pathophysiology
Clinical Presentation
Differential Diagnosis
Diagnosis of Acquired Thrombocytopenia
Chronic Fetal Hypoxia
Infections
Necrotizing Enterocolitis
Thrombocytopenia Secondary to Maternal Immune Thrombocytopenia
Vascular Consumption
Management
Etiology-Specific Treatment
Thrombocytopenia Due to Maternal Immune Thrombocytopenia
Vascular Consumption
Inherited Platelet Function Disorders
Chapter 107. Bernard–Soulier Syndrome and Other GPIb-IX-Related Receptor Defects
Bernard–Soulier Syndrome
Benign Mediterranean Macrothrombocytopenia
Thrombocytopenia and Velocardiofacial (DiGeorge) Syndrome
Platelet-Type von Willebrand Disease (Gain of Function Mutation of GPIb-IX)
Chapter 108. Glanzmann Thrombasthenia
Pathophysiology
Variant Glanzmann Thrombasthenia
Diagnosis
Management
Chapter 109. Other Platelet Glycoprotein Disorders
Glycoprotein VI
Glycoprotein IV
Glycoprotein Ia/IIa
Future
Chapter 110. Platelet Storage Granule Defects
Diagnosis
Management
Hermansky–Pudlak Syndrome
Chediak–Higashi Syndrome
Gray Platelet Syndrome(s)
White Platelet Syndrome
Other Granule Defects
Chapter 111. Failure to Release and Aspirin-Like Defects
Examples of Failure of Granule Release and Aspirin-Like Defects
Thromboxane Pathway Defects
ADP/ATP Receptor Defects
Defects in Platelet Intracellular Signaling Pathways
Defects in Platelet Procoagulant Activity
Diagnosis
Management
Chapter 112. Other Platelet Abnormalities
Platelet Abnormality as a Side Effect of Medications and Supplements
Platelet Abnormalities Related to Shear Stress and Artificial Surfaces
Thrombocytopathy Associated with Systemic Derangements
Uremia
Trauma and Resuscitation
Acquired Inhibitors of Platelet Function
Chapter 113. Acquired Platelet Disorders
Drug-Induced Platelet Dysfunction
Immune-Mediated Acquired Platelet Disorders
Systemic Disorders with Acquired Platelet Dysfunction
Acquired Platelet Disorders Complicating Bone Marrow Disorders
Diagnostic Approach
Treatment of Acquired Platelet Disorders
Immune Thrombocytopenia
Chapter 114. Acute (Childhood) Immune Thrombocytopenia
Pathophysiology
Clinical Manifestations
Diagnosis
Clinical Evaluation
Laboratory Evaluation
Differential Diagnosis
Management
Chapter 115. Chronic Immune Thrombocytopenia
Pathophysiology
Clinical Manifestations
Laboratory Evaluation
Differential Diagnosis
Management
First-Line Therapies
Splenectomy
Refractory Immune Thrombocytopenia
Chapter 116. Drug-Induced Thrombocytopenia
Pathophysiology
Decreased Production
Increased Destruction
Hapten-Induced Antibody
Drug-Dependent (Quinine Type) Antibody Formation
GPIIb/IIIa Inhibitors
Drug-Induced Antibody
Immune Complex
Apoptosis
Clinical Manifestations
Diagnosis
Clinical Evaluation
Laboratory Evaluation
Differential Diagnosis
Management
Chapter 117. Heparin-Induced Thrombocytopenia
Epidemiology
Heparin-Related Risk Factors
Host-Related Risk Factors
Pathophysiology
Diagnosis
Clinical Diagnosis
Timing of Platelet Count Fall
Degree of Platelet Count Fall
Thrombosis and Hemorrhage
Unusual Clinical Sequelae
Alternative Causes of Thrombocytopenia
Clinical Scoring Systems
Laboratory Diagnosis
Management
Argatroban
Bivalirudin
Danaparoid
Fondaparinux
Direct Oral Anticoagulants
Limitations of Current Therapies
Transitioning to Oral Therapy
Duration of Anticoagulation
Intravenous Immunoglobulin
Platelet Transfusion
Heparin Reexposure in Patients With a History of Heparin-Induced Thrombocytopenia
Chapter 118. Vaccine-Induced Immune Thrombotic Thrombocytopenia
Clinical Presentation
Pathophysiology
Diagnosis
Treatment
VITT after Non-adenoviral Vector-Based Vaccines
Administration of Vaccine Boosters in VITT Patients
Summary
Chapter 119. Autoimmune Lymphoproliferative Syndrome
Pathophysiology
Genetics
Clinical Manifestations
Diagnosis
Differential Diagnosis
Management
Immune Mediated Coagulopathies
Chapter 120. Hemolytic Uremic Syndrome
Pathophysiology
Hemolytic Uremic Syndrome
Atypical Hemolytic Uremic Syndrome
Clinical Manifestation
Laboratory Features and Diagnosis
Complete Blood Count and Coagulation Markers
Renal Function
Complement Levels
Differential Diagnosis
Management/Prognosis
Hemolytic Uremic Syndrome
aHUS
Chapter 121. Thrombotic Thrombocytopenic Purpura
Pathophysiology
Epidemiology
Clinical Manifestations
Diagnosis
Differential Diagnosis
Management
Refractory Disease
Relapse
Congenital Thrombotic Thrombocytopenic Purpura
Non-Immune TTP
Chapter 122. Antiphospholipid Syndrome
Antigenic Specificities and Pathophysiology of Antiphospholipid Antibodies
β2-glycoprotein I
Other Antigenic Targets of Antibodies Associated With Antiphospholipid Syndrome
Clinical Manifestations of the Antiphospholipid Syndrome
Venous and Arterial Thromboembolism
Pregnancy Complications
Noncriteria Clinical Manifestations Associated With Antiphospholipid Syndrome
Catastrophic Antiphospholipid Syndrome
Pediatric Antiphospholipid Syndrome
Treatment of Patients with Antiphospholipid Syndrome
Thrombotic Antiphospholipid Syndrome Treatment
Obstetric Antiphospholipid Syndrome Treatment
Management of Noncriteria Clinical Manifestations
Catastrophic Antiphospholipid Syndrome Treatment
Refractory Antiphospholipid Syndrome Treatment
Management of Patients with Clinical Manifestations and Low-Titer Antiphospholipid Antibody Positivity
Management of Asymptomatic Antiphospholipid Antibody-Positive Patients
Antiphospholipid Syndrome Treatment Duration and Monitoring
Future Management of Antiphospholipid Syndrome
Congenital Bleeding Disorders
Chapter 123. von Willebrand Disease
The Protein
Platelet-Derived von Willebrand Factor
Pathophysiology
Overview of Molecular Variants and Prevalence
Type 1 von Willebrand Disease
Type 2 von Willebrand Disease
Type 2A von Willebrand Disease
Type 2B von Willebrand Disease
Type 2M von Willebrand Disease
Type 2N von Willebrand Disease
Type 3 von Willebrand Disease
Platelet-Type or Pseudo-von Willebrand Disease
Diagnosis
von Willebrand Disease Screening Tests
Acquired von Willebrand Syndrome
Management
Antifibrinolytics
Desmopressin
Chapter 124. Hemophilia A
Pathophysiology
Clinical Manifestations
Diagnosis
Differential Diagnosis
Management
Comprehensive Care
Factor Concentrates
Prophylaxis
Desmopressin
Antifibrinolytic Therapies
Complications
Infectious Complications
Inhibitors
Joint Disease
Recent Advances in Hemophilia Care
Gene Therapy
Nonfactor Replacement Products
Chapter 125. Hemophilia B
Pathophysiology
Genetics
Clinical Manifestations
Diagnosis
Differential Diagnosis
Management
Comprehensive Care
Factor Concentrates
Antifibrinolytic Therapies
Gene Therapy
Nonfactor Replacement Therapies
Complications
Infectious Complications
Inhibitors
Nephrotic Syndrome
Joint Disease
Chapter 126. Factor XI Deficiency
Pathophysiology
Role in Coagulation
Genetics
Clinical Manifestations
Diagnosis
Management
Chapter 127. Factor VII Deficiency
Pathophysiology
Genetics
Clinical Manifestations
Diagnosis
Differential Diagnosis
Management
Chapter 128. Inherited Deficiencies of Factor II, Factor V, & Factor X
Pathophysiology
Role in Coagulation
Genetics
Diagnosis
Differential Diagnosis
Management
Chapter 129. Congenital Disorders of Fibrinogen
Pathophysiology
Role in Coagulation
Genetics
Clinical Manifestations
Diagnosis
Differential Diagnosis
Management
Chapter 130. Factor XIII, α2-Antiplasmin, and Plasminogen Activator Inhibitor Type 1 Deficiencies
Pathophysiology
Role in Coagulation
Genetics
Clinical Manifestations
FXIII Deficiency
Α2-AP Deficiency
PAI-1 Deficiency
Diagnosis
Differential Diagnosis
Management
FXIII Deficiency
α2-AP and PAI-1 Deficiencies
Acquired Bleeding Disorders
Chapter 131. Bleeding Disorders in Pregnancy
Congenital Disorders
Preconception and Prenatal Counseling
von Willebrand Disease
Management of Labor and Delivery
Management of Bleeding and Breastfeeding
Carriers of Hemophilia A or B
Mode of Delivery in Carriers of Severe Hemophilia
Factor XI Deficiency
Platelet Function Defects
Other Inherited Defects
Delivery of a Fetus With a Potential Bleeding Disorder
Acquired Disorders
Acquired Factor VIII Inhibitors
Thrombocytopenia
Gestational Thrombocytopenia
Immune Thrombocytopenia
Disseminated Intravascular Coagulation
Hemolysis, Elevated Liver Enzymes, and Low Platelets
Acute Fatty Liver of Pregnancy
Thrombotic Thrombocytopenia Purpura
Chapter 132. Vascular Bleeding Disorders
Hereditary Vascular Malformations
Hereditary Hemorrhagic Telangiectasia (Osler–Weber–Rendu Disease)
Hereditary Connective Tissue Disorders
Ehlers–Danlos Syndromes
Pseudoxanthoma Elasticum
Acquired Vascular Disorders
Purpura Simplex (Idiopathic Purpura)
Senile Purpura
Purpura Due to Infections
Scurvy
Henoch–Schönlein Purpura
Chapter 133. Hemostasis in Liver Disease
Decreased Synthesis of Pro- and Anticoagulant Factors
Vitamin K Deficiency
Thrombocytopenia
Fibrinogen
Clinical Manifestations
Monitoring Laboratory Parameters in Liver Disease
Management
Anticoagulation in Liver Disease
Chapter 134. Bleeding Risks With Vitamin K Deficiency
Pathophysiology
Etiology
Clinical Features
Diagnosis
Differential Diagnosis
Management
Chapter 135. Bleeding Risks With Cardiac Disease
Cardiac Disease
Cardiac Surgery
Left Ventricular Assist Devices
Screening Laboratory in Cardiopulmonary Bypass Bleeding Assessment
Chapter 136. Bleeding Risks With Renal Disease
Pathophysiology
Vessel Wall-Related Factors
Biochemical Changes Due to Uremia
Role of Red Cell Mass
Role of the Fibrinolytic Pathway
Role of Platelets (Platelet Dysfunction)
External Factors
Nephrotic Syndrome
Clinical Manifestations
Diagnosis
Management
Prophylactic Strategies to Prevent Bleeding
Acute Bleeding Control
Chapter 137. Bleeding Risks With Cancer
Etiology and Pathogenesis
Vascular Etiology
Platelet Disorders
Coagulation and Fibrinolysis
Clinical Manifestations
Diagnosis
Management
Chapter 138. Disseminated Intravascular Coagulopathy
Pathophysiology
Clinical Manifestations
Diagnosis
Differential Diagnosis
Management
Blood Product Support
Anticoagulant Pathway Therapy
Anticoagulants
Antifibrinolytic Therapy
Chapter 139. Thrombosis in Sickle Cell Disease
Alteration of Coagulation
Challenges in Thrombosis Prevention in SCD
Chapter 140. COVID-19-Related Coagulopathy
Mechanisms Involved in COVID-19 Coagulopathy
Endothelial Injury and Activation
Involvement of Native Immunity
Activation of Coagulation
Anticoagulation
Chapter 141. Platelets in COVID-19 Coagulopathy
Platelet Count
Platelet Production
Platelet Function
Platelet–Leukocyte Aggregates
Antiplatelet Agents
Summary
Chapter 142. Acquired Coagulation Factor Inhibitors
Inhibitors of Factor VIII
Pathophysiology and Epidemiology
Clinical Manifestations
Diagnosis
Management
Hemostatic Treatment
Eradication of the Inhibitor
Inhibitors of von Willebrand Factor
Pathophysiology and Epidemiology
Clinical Manifestations
Diagnosis
Management
Hemostatic Therapy
Antibody Eradication
Inhibitors of Factor V
Inhibitors of Prothrombin and Thrombin
Laboratory Testing of Coagulation
Chapter 143. Overview of Purposes of Hemostasis Testing and Common Sources of Error
Screening to Assess Risk of Hemorrhage in Otherwise Asymptomatic Patients Before an Invasive Procedure
Measuring the Effect of Hemostasis System-Modifying Drugs
Monitoring Hemostasis System Under Stress and Assessing the Need for Replacement Products
Diagnostic Workup to Assess Risk of Recurrent Thrombosis or Bleeding in Patients With Unexpected Thromboembolic or Hemorrhagic Event
Sources of Diagnostic Errors in Hemostasis Testing
Wrong Timing of the Test
Wrong Test
Wrong Patient
Wrong Sample Type
Sample Collection
Compromised Sample
Sample Handling
Postanalytic Issues
Chapter 144. Pediatric Reference Ranges in Coagulation Testing
Routine Coagulation Testing
Coagulation Factors Levels
Endothelial Derived Hemostatic Factors
Anticoagulants in Children
Fibrinolysis in Children
Platelet Studies
Viscoelastic Testing in Children
Other Vascular Conditions
Chapter 145. Hematology and Coagulation in Gender Diverse People
Introduction to Gender Diversity
Hematology in Gender Diverse People
Coagulation in Gender Diverse People
Chapter 146. Prothrombin Time
Quick and Owren Prothrombin Time
International Normalized Ratio
Test Limitations
Temperature and Time of Sample Storage
Effect of Collection Tubes, High Hematocrit, Underfilled Tubes, and Anemia
Plasma Discoloration
Effect of Medications
Lupus Anticoagulants
Factor VII R304Q Variant
Test Interpretation
Chapter 147. Activated Partial Thromboplastin Time
Test Utility
Test Limitations
Interlaboratory Variation
Preanalytical and Analytical Considerations
Storage Requirements
Effect of Collection Tubes, High Hematocrit, Underfilled Tubes, and Anemia
Plasma Discoloration
Effect of Medications
Lupus Anticoagulant
Effect of High FVIII
Test Interpretation
Laboratory Assessment of Coagulation Disorders
Chapter 148. Mixing Studies
Methods
Interpretation
Test Performance
Sources of Error
Heparin
Therapeutic Agents
Weak Inhibitors
Quality Assurance
Chapter 149. Coagulation Factor Testing
Methods
FVIII Activity
FVIII Antigen
FIX Activity
FIX Antigen
FXI and FXII Activities
FII, FV, FVII, and FX Activities
FXIII Activity
FXIII Antigen
Test Performance
Sources of Error
Quality Assurance
International Standards
Chapter 150. Testing of Nonfactor Therapies: Emicizumab
Emicizumab: Mechanisms of Action
Emicizumab Indications
Emicizumab Interference With Coagulation Testing
How to Monitor Patients With Factor VIII Inhibitors on Emicizumab
How to Monitor Emicizumab
Emicizumab Inhibitors
Adverse Events
Chapter 151. Specific Factor Inhibitor Testing
Methods and Test Interpretation
FVIII Inhibitors
FIX Inhibitors
FXI Inhibitors
FV, FVII, FX, and FXIII Inhibitors
von Willebrand Factor Inhibitors
Sources of Error
Chapter 152. Thrombin Time and Fibrinogen Evaluation
Physiologic Role of Fibrinogen
Clinical Significance
Testing Overview
Functional Fibrinogen Determination
Clauss Fibrinogen Test
Prothrombin Time–Based Tests
Viscoelastic Testing
Functional Fibrinogen Test Interpretation
Test Limitations
Total Fibrinogen Determination
Test Interpretation
Test Limitations
Thrombin Time
Test Interpretation
Thrombin Time 1:1 Mix
Test Limitations
Chapter 153. Laboratory Diagnosis of Inherited von Willebrand Disease
Methods
von Willebrand Factor Antigen
Ristocetin Cofactor
Glycoprotein Ib Binding Assays
Monoclonal Antibody Assays
Factor VIII Coagulant Activity
Collagen Binding Assay
Ristocetin-Induced Platelet Aggregation
von Willebrand Factor Multimers
von Willebrand Factor Binding to Platelets
Factor VIII Binding to von Willebrand Factor
von Willebrand Factor Propeptide
DNA Sequencing
von Willebrand Factor Inhibitor
Test Interpretation
Type 1 von Willebrand Disease
Type 2 von Willebrand Disease
Type 2A
Type 2B
Type 2M
Type 2N
Type 3 von Willebrand Disease
Platelet-Type or Pseudo–von Willebrand Disease
Sources of Error
Chapter 154. Laboratory Diagnosis of Acquired von Willebrand's Syndrome
Methods
Test Interpretation
Sources of Error
Chapter 155. Laboratory Assessment of Treatment of von Willebrand Disease
Methods
Treatment Modalities
Desmopressin
von Willebrand Factor Replacement
Adjunctive Therapies
Chapter 156. Measurement of Platelet Count, Mean Platelet Volume, and Reticulated Platelets
Methodology Overview
Manual Platelet Counts
Immunoreactive Platelet Count
Coulter Impedance Method
Optical Count
Test Limitations
General Considerations
Coulter Impedance
Optical Counting
Mean Platelet Volume
Test Limitations
Reticulated Platelets
Test Limitations
Chapter 157. Platelet Function Analyzer
Methods
Test Interpretation
Sources of Error
False Positive
False Negative
Quality Assurance
Chapter 158. Thromboelastography/Thromboelastometry
Principles of Testing
Result Interpretation
Reference Ranges
Use of Results to Manage Transfusion Protocols and Pharmacologic Therapy
Fibrinolysis Detection
Hypercoagulability Assessment
Platelet Function Assessment
TEG Platelet Mapping and ROTEM Platelet
Test Limitations
Quality of Data
Sample Handling
Correlation With Conventional Test Modalities
Chapter 159. Platelet Aggregation Studies
Methods
Light-Transmission Aggregometry
Whole-Blood Aggregometry
Platelet Adenosine Triphosphate Release
Test Interpretation
Sources of Error
Chapter 160. Laboratory Diagnosis of Platelet Functional Defects
Methods
Platelet Function Analyzer
Platelet Aggregation Studies
Electron Microscopy
Flow Cytometry
DNA Sequence Analysis
Test Interpretation–Genetic Platelet Function Disorders
Primary Aggregation Defects
Storage Pool Disorders
Release Defects
Adhesion Defects
Receptor Defects
Platelet Procoagulant Activity Defects
Test Interpretation–Acquired Platelet Function Defects
Uremia
Myeloproliferative Disorders
Hepatic Disease
Gammopathies
Autoimmunity to Platelet Proteins
Disseminated Intravascular Coagulopathy
Extracorporeal Membrane Oxygenation
Chapter 161. Confirmatory Testing for Diagnosis of Platelet Disorders
Platelet Transmission Electron Microscopy
Platelet Ultrastructural Defects
Shape and Size Abnormalities
α-Granule Defects
Abnormal α-Granule Ultrastructure
Dense Granule Deficiency
Hermansky–Pudlak Syndrome
Wiskott–Aldrich Syndrome and X-Linked Microthrombocytopenia
Abnormal Inclusions in Neutrophils
MYH9 Mutation–Related Disorders
Chediak–Higashi Syndrome
Flow Cytometric Studies
Glanzmann Thrombasthenia
Macrothrombocytopenia in Bernard–Soulier Syndrome, Mediterranean Macrothrombocytopenia, and DiGeorge or Velocardiofacial Syndrome
Collagen Receptor Deficiencies
Platelet Functional Test by Flow Cytometry
Molecular Genetic Testing
Confirmatory Testing Algorithm
Chapter 162. Antiplatelet Therapy Monitoring
Methods
Light-Transmission Aggregometry
Whole-Blood Aggregometry
Platelet Function Analyzer-100
VerifyNow
Plateletworks
Thromboelastography
Flow Cytometry
Measurement of Thromboxane A2 Metabolites
Bleeding Time
Test Interpretation and Sources of Error
Aspirin
P2Y12 Antagonists
Phosphodiesterase Inhibitors
GPIIb/IIIa Inhibitors
Chapter 163. Laboratory Evaluation of Factor XIII Deficiency
Factor XIII Activity Assays
Clot Solubility
Quantitative Factor XIII Activity Assays
Amine Incorporation Assay
Ammonia Release Assay
Antigenic Assays
Test Limitations
Clot Solubility
Amine Incorporation
Ammonia Release Assays
Antigenic Assays
Test Interpretation
Chapter 164. Fibrinolytic Testing
Physiology
Hereditary Fibrinolytic Bleeding
Plasminogen Activator Inhibitor 1 Deficiency
Antiplasmin Deficiency
Acquired Fibrinolytic Bleeding Disorders
Cardiopulmonary Bypass Surgery
Liver Transplantation
Shock/Trauma/Disseminated Intravascular Coagulation
Fibrinolytic Thrombosis
Increased Plasminogen Activator Inhibitor 1
Dysfibrinogen
Plasminogen Deficiency
Increased Thrombin-Activatable Fibrinolysis Inhibitor
Chapter 165. Age-Adjusted D-Dimer Cut Offs to Rule out Thrombosis
D-Dimer to Rule Out VTE
D-Dimer in the Elderly
D-Dimer in Children
Ethnicity and Gender
Pregnancy
D-Dimer in Disseminated Intravascular Coagulopathy
D-Dimer in Aortic Dissection
Summary
Chapter 166. Laboratory Techniques in Fibrinolysis Testing
Screening Tests
Euglobulin Lysis Time
Thromboelastometry/Thromboelastography
Specific Tests
Fibrinogen: See Chapter 155
D-Dimer
Plasminogen
Antiplasmin
Tissue Plasminogen Activator
Plasminogen Activator Inhibitor One
Thrombin Activatable Fibrinolysis Inhibitor
Tests for Hyercoagulable State
Chapter 167. Laboratory Evaluation of Long-Term Thrombophilic Disorders
Testing Recommendations
Testable Thrombophilia Risk Factors
Deleterious Mutations in Genes Encoding Natural Anticoagulants
Increased Concentration, Gain of Function, or Delayed Inactivation of Procoagulant Proteins
Hereditary Nonhemostatic Factors That Result in Prothrombotic State
Acquired Testable Risk Factors
Chapter 168. Thrombophilia Testing in the Pediatric Population
Laboratory Evaluation of Thrombophilia
Impact of Thrombophilia in Childhood Thrombosis
Screening Recommendations
Chapter 169. Antithrombin Testing
Physiologic Role and Mechanism of Action
Congenital Antithrombin Deficiency
Testing Indications
Preanalytical Considerations
Testing Overview
Testing Methodologies
Activity Determination in the Presence of Heparin
Test Interpretation
Sources of Error
Antigenic Tests
Test Interpretation
Sources of Error
Determining the Subtype of Type II Antithrombin Deficiency
Chapter 170. Protein C Deficiency Evaluation
Epidemiology and Clinical Presentation
Testing Recommendations
Protein C Deficiency Testing Overview
Diagnostic Guidelines
Timing of the Test
Test Selection
Protein C Testing Methodologies
Clottable Protein C
Chromogenic Protein C Activity
Protein C Antigen
DNA-Based Tests
Limitations of Protein C Testing
Clot-Based Protein C Activity Determination
Chromogenic Protein C Activity Determination
Protein C Antigen
Test Interpretation
Chapter 171. Protein S Deficiency Evaluation
Physiologic Role
Nonhemostatic Function of Protein S
Epidemiology
Test Recommendations
Types of Protein S Deficiency
Diagnostic Guidelines
Testing Modalities
Protein S Activity
Analytical Interferences of Protein S Activity Testing
Protein S Free Antigen
Protein S Total Antigen
C4b-Binding Protein
Molecular Testing
Test Interpretation
Chapter 172. Testing for Activated Protein C Resistance
Activated Protein C Resistance Assays
Methods
Test Interpretation
Test Performance
Sources of Error
False Positives
Discrepancies Between APC Resistance Assay and Molecular Testing for FVL
Chapter 173. Molecular Testing for Factor V Leiden and Prothrombin Gene Mutations
Factor V Leiden
Prothrombin Gene Mutation
Diagnostic Testing
Factor V Leiden
Prothrombin Mutation
Methods
Test and Result Interpretation
Sources of Error
Chapter 174. Chronic Elevated Levels of Factor VIII and Other Coagulation Factors
Elevated Factor VIII
Elevated Factor IX
Elevated Factor XI
Elevated Prothrombin
Other Coagulation Factors
Chapter 175. Acquired Prothrombotic Conditions
Classic Acquired Prothrombotic Conditions
Role of Inflammation in Acquired Prothrombotic Conditions
Role of Infection in Acquired Prothrombotic Conditions
Recently Utilized (Nontraditional) Laboratory Assays (Table 175.2)
von Willebrand factor
Thromboelastography and Thrombin Generation Testing
Microparticles
Concluding Remarks
Chapter 176. Laboratory Evaluation of Heparin-Induced Thrombocytopenia
Antigen Assays
Solid-Phase Enzyme Immunoassays
Fluid-Phase Enzyme Immunoassays
Rapid Immunoassays
Particle Gel Immunoassay
Particle Immunofiltration Assay
Latex Immunoassay
Chemiluminescent Immunoassays
Antigen Assay Interpretation
Platelet Activation (Functional) Assays
Platelet Aggregation Test
Serotonin Release Assay
Heparin-Induced Platelet Activation Test
Interpretation of Functional Platelet Assays
Other Methodologies
Chapter 177. Laboratory Evaluation of Thrombotic Thrombocytopenic Purpura
Measurement of ADAMTS13 Activity
Whole Substrate Methods
Peptide Substrate Methods
FRET-VWF73 Assay
Other Peptide Methods
Test Limitations
ADAMTS13 Activity Test Interpretation
Use in Diagnosis
Use in Prognosis
Measurement of Anti-ADAMTS13 Autoantibodies
Interpretation
Chapter 178. Laboratory Diagnosis of Lupus Anticoagulant and Antiphospholipid Antibodies
Antiphospholipid Syndrome Criteria Assays
Prevalence of Antiphospholipid Antibodies and Appropriateness of Testing
Lupus Anticoagulant Tests
Activated Partial Thromboplastin Time Tests
Dilute Russell Viper Venom Time
Antiphospholipid Immunoassays
Anticardiolipin Antibody Assay
Anti-β2GPI Antibody Assay
Multipositivity for Antiphospholipid Syndrome Criteria Assays and Clinical Risk
“Noncriteria” Laboratory Assays
Anticardiolipin and Anti-β2-glycoprotein I IgA Assays
Antiphosphatidylserine/Prothrombin Assays
Other Antiphospholipid Immunoassays
Antidomain I of β2GPI Assay
Annexin A5 Assays
Genetic, Genomic, and Proteomic Studies in Antiphospholipid Syndrome
Chapter 179. D-DIMER Testing in COVID Coagulopathy
Laboratory Support of Anticoagulation
Chapter 180. Laboratory Monitoring for Heparins, Fondaparinux, Direct Thrombin Inhibitors, and Oral Anti-Xa Medications
Unfractionated Heparin
Testing Recommendations
Testing Modalities
Partial Thromboplastin Time Correlation/Calibration for Heparin Monitoring
Anti-Xa Assays for Direct Measurement of Heparin Activity
Preanalytical Considerations and Result Interpretation
Result Interpretation
Low-Molecular-Weight Heparin and Fondaparinux
Testing Recommendations
Testing Modalities
Test Interpretations
Direct Anti-Xa Inhibitors
Testing Indications
Test Modalities
Test Interpretation
Direct Thrombin Inhibitors
Testing Indications
Testing Modalities
Activated Partial Thromboplastin Time
Thrombin-Based Assays
Test Interpretation
Reversal Agents
Chapter 181. DOAC Interferences in Coagulation Testing: DOAC Detection, Removal and Monitoring
What are DOACs
Advantages
DOAC Interference With Coagulation Testing
DOACs Removing Protocols
Monitoring of DOACs
Issues With Monitoring DOACs
DOAC to Heparin Transition and Vice Versa
Warfarin and DOACs
Antidote and Reversing Protocols
Chapter 182. Laboratory Support for Warfarin Monitoring
Laboratory Testing for Warfarin Monitoring
Prothrombin Time
Interpretation
Special Considerations and Sources of Error
Variability in Responsiveness to Thromboplastin Reagents
Standardization of Reporting
Point-of-Care International Normalized Ratio Testing
Abnormal Warfarin Responsiveness
Genetic Factors
Environmental and Drug Interactions
Chapter 183. Anticoagulation During Mechanical Circulatory Support Devices
Mechanical Circulatory Support Devices
Left Ventricle to Aorta Devices
Left Atrium to Systemic Artery Devices
Right Atrium to Pulmonary Arterial Devices
VA-ECMO Devices
Anticoagulation
Unfractionated Heparin
Direct Thrombin Inhibitors
Outcomes With Differing Anticoagulation Agents
Emerging Topics in Hemostasis Testing
Chapter 184. Molecular Testing in Coagulation
Bleeding
Thrombosis
Platelet Disorders
Controversial Coagulopathic Entities
Hyperhomocysteinemia and Methylenetetrahydrofolate Reductase
von Willebrand Disease
Fibrinogen
Protein S
Summary
Chapter 185. Circulating Microparticles
Composition of Microparticles
Classification of Microparticles
Mechanisms of Microparticle Release
Role of Microparticles
Microparticles in Human Disease
Venous Thromboembolism
Cardiovascular Disease
Sepsis
Thrombotic Thrombocytopenic Purpura
Heparin-Induced Thrombocytopenia
Preeclampsia
Processing of Microparticles
Methods for Detection of Microparticles
Microparticle Size and Count
Cellular Derivation of Microparticles
Platelet and Red Blood Cell Microparticles
Endothelial-Derived Microparticles
Monocyte-Derived Microparticles
Causation Versus Association
Therapeutic Opportunities
Chapter 186. Thrombin Generation Assays
Assay Methodology Overview
Test Interpretation
Test Limitations
Chapter 187. Diagnostic Use of Venoms
Fibrinogen Assessment
Reptilase Time
Principle of the Tests and Interpretation
Meizothrombin Assessment
Ecarin Clotting Time
Principles of the Test and Interpretation
Factor V Assessment
Factor X Assessment
RVV-X From Russell's Viper Venom
Principles and Interpretation of the Test
Lupus Anticoagulant Assessment
Dilute Russell's Viper Venom Time
Textarin/Ecarin Ratio
Taipan Venom Time
Protein C Assessment
Protac
Principles of the Test and Interpretation
Clot-Based Assay
Chromogenic Assay
Resistance to Activated Protein C
Pefakit APCR Factor V Leiden
dRVVT-Based APCR
Botrocetin
Therapeutics Use of Exogenous Factors
Capoten (Captopril)
Aggrastat (Tirofiban)
Integrilin (Eptifibatide)
Angiomax (Bivalirudin)
Byetta (Exenatide)
Prialt (Ziconotide)
Chapter 188. Laboratory Testing of Contact Factors
What is the Contact Pathway?
Role of Contact Pathway in Angioedema
Contact Pathway Factor Deficiency
Role of Contact Pathway in Fibrinolysis
Role of Contact Pathway in Thrombosis
Activation of the Contact Pathway by Medical Devices
Inhibitors of Contact Pathway
Laboratory Assessment of Contact Pathway
Abbreviations
General Handbook References
Index

Beth H. Shaz

Beth H. Shaz, MD, is Chief Medical and Scientific Officer, Executive Vice President at New York Blood Center, and Adjunct Assistant Professor, Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University. Beth is responsible for all medical and scientific activities throughout the NYBC network, which includes Rhode Island Blood Center, Innovative Blood Resources (Memorial Blood Center and Nebraska Blood Center), Community Blood Center of Greater Kansas City, and Blood Bank of Delmarva. Medical activities comprise of hemophilia services, clinical apheresis services, perioperative autologous transfusion services, cellular therapy, medical education, medical consultation, transfusion services, bone marrow donor recruitment, and donor management. Scientific activities include basic science at the Lindsey F. Kimball Research Institute and Comprehensive Cell Solutions (CCS), which contains translational and clinical research. NYBC’s scientific and medical activities focus on transfusion medicine, cell therapy, regenerative medicine, infectious disease, hematology, and personalized medicine. Beth is an editor of ten books in transfusion medicine, author of over 130 articles pertaining to transfusion medicine. She is an associate editor of TRANSFUSION and on the editorial board of BLOOD. Previously, she was an Associate Professor at Emory University School of Medicine and director of the transfusion service at Grady Memorial Hospital. Also, she was an instructor at Harvard Medical School and associate director of the transfusion service at Beth Israel Deaconess Medical Center in Boston. Beth received her MD with research distinction from the University of Michigan and BS in chemical engineering with distinction from Cornell University. She completed a general surgery internship at Georgetown University, an anatomic & clinical pathology residency at Beth Israel Deaconess Medical Center, and a transfusion medicine fellowship at Harvard Medical School.

Affiliations and expertise

Chief Medical and Scientific Officer and Executive Vice President, New York Blood Center and Adjunct Assistant Professor, Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA

Christopher D. Hillyer

Christopher D. Hillyer, MD, is President and CEO of New York Blood Center and Professor, Department of Medicine, Weill Cornell Medical College, New York, NY. Previously, he was the tenured, endowed Distinguished Service Professor, Department of Pathology and Laboratory Medicine, Emory University School of Medicine and served as director of the Emory Center for Transfusion and Cellular Therapies with responsibility for all aspects of clinical and academic transfusion medicine at Emory’s seven principle hospitals. Dr. Hillyer is an editor of twelve textbooks in transfusion medicine, author of over 160 articles pertaining to transfusion, human immunodeficiency virus, and herpes viruses, most notably cytomegalovirus. Nationally recognized as an expert in hematology and blood transfusion, Dr. Hillyer is also a past-president, board of directors of AABB and a former trustee of the National Blood Foundation. Dr. Hillyer has been awarded many million dollars in research funding from the National Institutes of Health, the Centers for Disease Control and Prevention and other agencies. He was an associate editor of Transfusion and serves on several other editorial boards. Dr. Hillyer was formally recognized for his work in Africa as part of the AABB/Emory cooperative agreement from the President’s Emergency Plan For AIDS Relief (PEPFAR), and is a recipient of two Tiffany Awards from the American Red Cross where he also served as a medical director and a member of their national Medical Advisory Board. He also received the 2014 Emily Cooley Award from AABB for his “significant commitment and contributions to the field of transfusion medicine through extensive teaching, mentoring and professional leadership, and the countless clinical, scientific and innovative resource materials he has created to educate others”. He is a co-founder of Transfusion & Transplantation Technologies, Inc (3Ti) and holds over 20 patents or patents pending. Dr. Hillyer is board certified in transfusion medicine, hematology, medical oncology and internal medicine. He received his BS from Trinity College, and his MD from the University of Rochester School of Medicine, with postgraduate training and fellowships in hematology-oncology, transfusion medicine and bone marrow transplantation at Tufts-New England Medical Center.

Affiliations and expertise

President and Chief Executive Officer, New York Blood Center and Professor, Department of Medicine, Weill Cornell Medical College, New York, NY, USA

Joseph (Yossi) Schwartz

Joseph (Yossi) Schwartz, MD, MPH received his MD from the Technion – Israel Institute of Technology and his MPH from Columbia University Mailman School of Public Health. He completed Internal Medicine & Hematology Fellowship in Israel and then completed Transfusion Medicine/Blood Banking fellowship at the New York Blood Center. He was as previously a Professor of Pathology & Cell Biology at the Columbia University Medical Center and served as the Director of the Transfusion Medicine & Cellular Therapy Service. He oversaw the Blood Bank, The Cell Therapy facility and the Apheresis unit.

Affiliations and expertise

Professor of Pathology, Molecular and Cell–based Medicine, Icahn School of Medicine, Mount Sinai, NY, USA

Morayma Reyes Gil

Morayma Reyes Gil, MD, PhD, is an associate professor in the Department of Pathology at Montefiore Medical Center (MMC) and Albert Einstein College of Medicine. As the director of hematology and special coagulation laboratories, Dr. Reyes Gil oversees all hematology and coagulation laboratories at all MMC hospitals, collaborates in clinical research and clinical trial studies and continues translational research in vascular biology. She started her career in academic pathology at the University of Washington as an assistant professor in the Department of Pathology and laboratory Medicine. Dr. Reyes Gil has been a recipient of several awards and research grants from private research foundations and from the National Institutes of Health. Dr. Reyes Gil is board certified in clinical pathology and has authored over 50 peer-reviewed articles in the field of vascular biology. Dr. Gil is a graduate of the University of Puerto Rico. She received her MD and PhD from the University of Minnesota. She then completed a residency in clinical pathology and specialized in coagulation and benign hematology at the University of Washington.

Affiliations and expertise

Director of Hematology and Coagulation Laboratories, Montefiore Medical Center and Associate Professor, Department of Pathology and Laboratory Medicine, Albert Einstein College of Medicine, New York, NY, USA

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Transfusion Medicine and Hemostasis

Clinical and Laboratory Aspects

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Beth H. Shaz

Christopher D. Hillyer

Joseph (Yossi) Schwartz

Morayma Reyes Gil

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