Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects
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Transfusion Medicine and Hemostasis - Beth H. Shaz
Abshire
Brief Table of Contents
Copyright Page
About the Editors
Contributors
Preface
Acknowledgments
I. Blood Banking and Transfusion Medicine
Chapter 1. Blood Banking and Transfusion Medicine – the Field, the Discipline and the Industry
Chapter 2. Brief History of Blood Transfusion
Chapter 3. Introduction to Quality Systems and Quality Management
Chapter 4. The Role of the Physician in the Blood Center
Chapter 5. The Blood Donor, Donation Process and Technical Aspects of Blood Collection
Chapter 6. Apheresis Blood Component Collections
Chapter 7. Recipient-specific Blood Donations
Chapter 8. Adverse Donor Reactions
Chapter 9. Component Preparation and Manufacturing
Chapter 10. Serologic Testing of Donor Products
Chapter 11. Overview of Infectious Disease Testing
Chapter 12. HIV Screening of Donor Products
Chapter 13. Hepatitis B Screening of Donor Products
Chapter 14. Hepatitis C Screening of Donor Products
Chapter 15. West Nile Virus Screening of Donor Products
Chapter 16. Syphilis, HTLV and Chagas Testing of Donor Products
Chapter 17. Bacterial Detection Methods
Chapter 18. The Role of the Transfusion Service Physician
Chapter 19. Pretransfusion Testing
Chapter 20. Antibody Identification
Chapter 21. Direct Antiglobulin Test
Chapter 22. ABO and H Blood Group Systems
Chapter 23. Rh Blood Group System
Chapter 24. Kell and Kidd Blood Group Systems
Chapter 25. MNS and Duffy Blood Group Systems
Chapter 26. Lewis, I and P Blood Group Systems
Chapter 27. Other Blood Group Systems, Collections and Antigens
Chapter 28. Red Blood Cells and Related Products
Chapter 29. Plasma Products
Chapter 30. Platelet Products
Chapter 31. Cryoprecipitate
Chapter 32. Granulocyte products
Chapter 33. Albumin and Related Products
Chapter 34. Human Immunoglobulin Preparations
Chapter 35. Rh Immune Globulin
Chapter 36. Irradiation of Blood Products
Chapter 37. Leukoreduction of Blood Products
Chapter 38. CMV-safe Blood Products
Chapter 39. Frozen Blood Products
Chapter 40. Washed Blood Products
Chapter 41. Volume-reduced Products
Chapter 42. Neonatal and Pediatric Transfusion Medicine
Chapter 43. Perinatal Transfusion Medicine
Chapter 44. Autoimmune Hemolytic Anemias
Chapter 45. Transfusion Management in Patients with Hemoglobinopathies
Chapter 46. Transfusion of Patients Undergoing HPC and Solid-organ Transplantation
Chapter 47. Transfusion of HIV-positive Patients
Chapter 48. Management of Patients Who Refuse Blood Transfusion
Chapter 49. Platelet Transfusion Refractory Patients
Chapter 50. Massive Transfusion
Chapter 51. Perioperative Blood Management
Chapter 52. Adverse Events and Outcomes Following Transfusion
Chapter 53. Febrile Non-hemolytic Transfusion Reactions
Chapter 54. Allergic, Anaphylactoid and Anaphylactic Reactions
Chapter 55. Acute Hemolytic Transfusion Reactions
Chapter 56. Delayed Hemolytic Transfusion Reactions
Chapter 57. Transfusion Associated Circulatory Overload
Chapter 58. Transfusion Related Acute Lung Injury
Chapter 59. Septic Transfusion Reactions
Chapter 60. Metabolic, Hypotensive and Other Acute Reactions and Complications
Chapter 61. Posttransfusion Purpura
Chapter 62. Transfusion Associated Graft Versus Host Disease
Chapter 63. Microchimerism
Chapter 64. Transfusion Related Immunomodulation
Chapter 65. Iron Overload
Chapter 66. Transfusion Transmitted Diseases
Chapter 67. Overview of Therapeutic Apheresis
Chapter 68. Therapeutic Plasma Exchange
Chapter 69. Therapeutic Erythrocytapheresis
Chapter 70. Therapeutic Thrombocytapheresis
Chapter 71. Therapeutic Leukapheresis
Chapter 72. Extracorporeal Photopheresis
Chapter 73. LDL Pheresis
Chapter 74. Immunoadsorption
Chapter 75. Therapeutic Phlebotomy
Chapter 76. HPC Products
Chapter 77. Tissue Banking in the Hospital Setting
II. Coagulation
Chapter 78. Overview of the Coagulation System
Chapter 79. Approach to the Bleeding Patient
Chapter 80. Congenital Thrombocytopenia
Chapter 81. Neonatal Alloimmune Thrombocytopenia
Chapter 82. Acquired Neonatal Thrombocytopenia
Chapter 83. Bernard-Soulier Syndrome and Other GPIb-IX-V Related Receptor Defects
Chapter 84. Glanzmann Thrombasthenia
Chapter 85. Platelet Storage-granule Defects
Chapter 86. Failure to Release and Aspirin-like Defects
Chapter 87. Acute (Childhood) Immune Thrombocytopenic Purpura
Chapter 88. Chronic Immune Thrombocytopenic Purpura
Chapter 89. Drug-induced Thrombocytopenia
Chapter 90. Heparin-induced Thrombocytopenia
Chapter 91. Autoimmune Lymphoproliferative Syndrome
Chapter 92. Hemolytic Uremic Syndrome
Chapter 93. Thrombotic Thrombocytopenic Purpura
Chapter 94. Antiphospholipid Antibody Syndrome
Chapter 95. von Willebrand Disease
Chapter 96. Hemophilia A
Chapter 97. Hemophilia B
Chapter 98. Congenital Disorders of Fibrinogen
Chapter 99. Factor XIII, α2-Antiplasmin and Plasminogen Activator Inhibitor-1 Deficiencies
Chapter 100. Factor XI Deficiency
Chapter 101. Factor VII Deficiency
Chapter 102. Factor II, Factor V and Factor X Deficiencies
Chapter 103. Bleeding Disorders in Pregnancy
Chapter 104. Vascular Bleeding Disorders
Chapter 105. Bleeding Risks with Liver Disease
Chapter 106. Bleeding Risks with Vitamin K Deficiency
Chapter 107. Bleeding Risks with Cardiac Disease
Chapter 108. Bleeding Risks with Renal Disease
Chapter 109. Bleeding Risks in Cancer
Chapter 110. Disseminated Intravascular Coagulopathy
Chapter 111. Acquired Coagulation Factor Inhibitors
Chapter 112. Introduction to Coagulation Testing
Chapter 113. Prothrombin Time and Activated Partial Thromboplastin Time
Chapter 114. Platelet Count
Chapter 115. Global Tests of Primary Hemostasis
Chapter 116. Platelet Aggregation Studies
Chapter 117. Laboratory Diagnosis of Genetic Platelet Function Defects
Chapter 118. Laboratory Diagnosis of Acquired Platelet Function Defects
Chapter 119. Laboratory Diagnosis of Immune Thrombocytopenic Purpura
Chapter 120. ADAMTS13 Testing
Chapter 121. Laboratory Diagnosis of Heparin-induced Thrombocytopenia
Chapter 122. Molecular Biology of von Willebrand Disease
Chapter 123. Laboratory Diagnosis of Inherited von Willebrand Disease
Chapter 124. Laboratory Diagnosis of Acquired von Willebrand Syndrome
Chapter 125. Laboratory Assessment of Treatment of von Willebrand Disease
Chapter 126. Coagulation Factor Testing
Chapter 127. Mixing Studies
Chapter 128. Specific Factor Inhibitor Testing
Chapter 129. Laboratory Diagnosis of Dysfibrinogenemia and Afibrinogenemia
Chapter 130. Laboratory Assessment of Fibrinolysis
Chapter 131. General Overview of the Hypercoaguable State
Chapter 132. Antithrombin Testing
Chapter 133. Proteins C, S and Z Testing
Chapter 134. Activated Protein C Resistance and Factor V Leiden Testing
Chapter 135. Prothrombin Gene Mutation Testing
Chapter 136. Laboratory Diagnosis of Hyperhomocysteinemia
Chapter 137. Laboratory Diagnosis of Lupus Anticoagulant and Antiphospholipid Antibodies
Chapter 138. Lipoprotein (a) Testing
Chapter 139. Laboratory Diagnosis of Factor Level Abnormalities Associated with Thrombosis
Chapter 140. Laboratory Management of DIC
Chapter 141. Laboratory Support for Heparin Monitoring
Chapter 142. Laboratory Support for Warfarin Monitoring
Chapter 143. Prothrombin Complex Concentrates
Chapter 144. von Willebrand Factor Concentrates
Chapter 145. Factor VIII Concentrates
Chapter 146. Factor IX Concentrates
Chapter 147. Factor VII Concentrates
Chapter 148. Antithrombin Concentrates
Chapter 149. Protein C Concentrates
Table of Contents
Copyright Page
About the Editors
Contributors
Preface
Acknowledgments
I. Blood Banking and Transfusion Medicine
Chapter 1. Blood Banking and Transfusion Medicine – the Field, the Discipline and the Industry
Blood Banking and Transfusion Medicine as a Discipline:
Blood Banking Defined:
Transfusion Medicine Defined:
The Blood Pipeline:
Additional Services:
Structure of Blood Banks and Transfusion Services:
Structure of Blood Banks and Transfusion Services within the US:
The Blood Industry:
Blood Banking and Transfusion Medicine as a Medical Specialty:
Subspecialties within Blood Banking and Transfusion Medicine:
The Role of the Physician in Blood Centers and Hospital Transfusion Services:
Oversight and Regulation of the Blood Industry:
The Federal Food and Drug Administration (FDA):
Other Applicable Regulatory Agencies:
Current Good Manufacturing Practices:
Oversight by Non-governmental Organizations:
AABB:
The Joint Commission:
College of American Pathologists:
Recommended Reading
Chapter 2. Brief History of Blood Transfusion
Early Transfusion:
Blood Groups:
Blood Storage:
Blood Derivatives:
Blood Component and Derivative Therapy:
Apheresis:
Adverse Effects of Transfusion:
Current Transfusion Medicine and Blood Banking:
Recommended Reading
Chapter 3. Introduction to Quality Systems and Quality Management
Compliance versus Quality:
Background:
Quality System Essentials:
Other Systems:
NCCLS GP26-A:
World Health Organization:
Quality as a Philosophy and Culture:
Additional and Related Terms:
Facility Inspections:
Recommended Reading
Chapter 4. The Role of the Physician in the Blood Center
Blood Center Table of Organization:
Specific Roles in Blood Center Core Operations:
Collections: Donor Selection and Complications:
Manufacturing and Processing:
Quality Systems and Laboratories:
Clinical Services:
Therapeutic Apheresis:
Immunohematology Reference, HLA and HPC Laboratories:
Financial Issues and Conflict of Interest:
Research and Advancement of the Field:
Recommended Reading
Chapter 5. The Blood Donor, Donation Process and Technical Aspects of Blood Collection
Blood Donor:
Blood Donation Process:
Recruitment Materials:
Educational Materials:
Registration:
Donor History Questionnaire:
Drug Therapy:
Medical History:
Donor Informed Consent:
Technical Aspects of Blood Donation:
Identification:
Preparation of the Venipuncture Site:
Phlebotomy:
Post-donation Care:
Donor Adverse Reactions:
Recommended Reading
Chapter 6. Apheresis Blood Component Collections
Apheresis RBC Collections:
Platelet Apheresis (Plateletpheresis) Collections:
Plasmapheresis Collections:
Recommended Reading
Chapter 7. Recipient-specific Blood Donations
Exceptional Medical Need:
Directed Donation:
Autologous Donation:
Chapter 8. Adverse Donor Reactions
Complications of Whole Blood Donation:
Minor Local Tissue Injury:
Nerve Injury:
Vasovagal Reactions:
Prolonged Recovery:
Arterial Puncture:
Complications of Apheresis Donations:
Apheresis-specific Reactions:
Hypocalcemia:
Machine Malfunction:
Allergic Reactions:
Platepheresis/Granulocytapheresis:
Approach to the Donor and Donation Process:
Recommended Reading
Chapter 9. Component Preparation and Manufacturing
Whole Blood:
Component Manufacturing:
Anticoagulant-preservative Solutions:
RBC Components:
Additive Solutions:
RBC Modification:
Plasma Components:
Cryoprecipitate:
Cryoprecipitate-reduced Plasma:
Plasma Derivatives:
Platelet Components:
Buffy Coat Platelets:
Platelet Modification:
Granulocytes:
Component Labeling:
Recommended Reading
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:
Recommended Reading
Chapter 11. Overview of Infectious Disease Testing
Background:
Approach to Testing:
Determination of Need and Requirement for Testing:
Selection of a Testing Methodology:
The Biology of an Infection, the Window Period and Testing Strategies:
Recommended Reading
Chapter 12. HIV Screening of Donor Products
Description:
Infection:
HIV Types:
Methods and Interventions to Ensure the Safety of the Blood Supply:
Donor Deferral:
Early HIV Testing – Anti-HBc and Anti-HIV:
HIV p24 Antigen:
Nucleic Acid Testing:
Automation:
Determination of Need and Requirement for Testing:
Approach to Testing:
Current US Methods and Approach:
International Considerations:
Recommended Reading
Chapter 13. Hepatitis B Screening of Donor Products
Determination of Need and Requirement for Testing:
Approach to Donor Testing:
HBsAg:
Anti-HBc:
HBV NAT:
International Considerations:
Recommended Reading
Chapter 14. Hepatitis C Screening of Donor Products
Determination of Need and Requirement for Testing:
Approach to Testing:
Anti-HCV:
HCV NAT:
International Standards:
Recommended Reading
Chapter 15. West Nile Virus Screening of Donor Products
Determination of Need and Requirement for Testing:
Approach to Testing:
Confirmatory Test:
Donor Deferral:
International Considerations:
Recommended Reading
Chapter 16. Syphilis, HTLV and Chagas Testing of Donor Products
Syphilis:
Background:
Determination of Need and Requirement for Testing:
Approach to Testing:
Donor Deferral:
International Considerations:
Human T-cell Lymphotropic Virus:
Background:
Determination of Need and Requirement for Testing:
Approach to Testing:
International Considerations:
Chagas Disease:
Description:
Determination of Need and Requirement for Testing:
Approach to Testing:
Confirmatory Tests:
Recommended Reading
Chapter 17. Bacterial Detection Methods
Methods to Avoid Bacterial Contamination:
Donor Screening:
Skin Preparation:
Methods to Reduce Bacterial Contamination:
Diversion Pouch:
Leukoreduction:
Methods to Inhibit or Inactivate Bacteria:
Cold Storage:
Storage Solutions:
Pathogen Inactivation:
Methods to Detect Contaminated Products:
Culture-based Methods:
Methods Performed Just Prior to Product Release:
Future Considerations:
Recommended Reading
Chapter 18. The Role of the Transfusion Service Physician
Organization chart:
Specific TM physician roles:
Transfusion Service:
Transfusion Service Management:
Quality Management:
Patient Care:
Transfusion Committee:
Audit:
Transfusion Practice Guidelines:
Maximum Surgical Blood Order:
Informed Consent:
Inventory Management:
Education:
Research:
TS Medical Direction Within Small- to Medium-sized Community Hospitals:
TM as a Career:
Recommended Reading
Chapter 19. Pretransfusion Testing
Patient Identification:
Specimen Requirements:
Method:
Immediate Spin Phase:
Anti-human Globulin Phase:
AHG Reagents:
Detection Techniques:
Tube Test:
Gel Test:
Solid Phase Test:
Automation:
ABO Blood Type:
D Type:
D Type of a Blood Product:
Antibody Screen:
Blood Component Selection:
ABO Compatibility:
D Compatibility:
Crossmatch:
Immediate Spin Crossmatch:
Electronic Crossmatch:
AHG Crossmatch:
Neonates:
Labeling and Release of Blood Components:
Causes of Unexpected Test Results:
Quality Assurance:
Recommended Reading
Chapter 20. Antibody Identification
Antibody Identification Panel:
Determination of Clinical Significance:
History of Antibody:
Indication:
Specimen Requirements:
Method:
Panel of RBCs of Known Antigenic Composition:
RBC Phenotype:
Prewarm Technique:
Cold Antibody Screen:
Enzyme-treated RBCs:
Neutralization:
Adsorption:
Autologous Adsorption:
Allogeneic Adsorption:
Blood Component Selection:
Warm Autoimmune Hemolytic Anemia:
Paroxysmal Nocturnal Hemoglobinuria (PNH):
Crossmatch:
Warm Autoantibodies:
Neonates:
Quality Assurance:
Recommended Reading
Chapter 21. Direct Antiglobulin Test
Indication:
Specimen Requirements:
Method:
Evaluation of a Positive DAT:
Eluate:
Panagglutinin:
Non-reactive Eluate:
Enhancement of Reactivity:
False-negative DAT:
False-positive DAT:
Clinical Significance of a Positive DAT:
Recommended Reading
Chapter 22. ABO and H Blood Group Systems
Antigens:
ABO variants:
Expression:
Antibodies:
Antibody Titers:
Plasma-rich Blood Components:
Solid Organ Transplantation:
Incompatible HPC Transplantation:
Typing Discrepancies:
Resolving Discrepancies Due to Absence of Expected Antigens:
Resolving Discrepancies Due to Unexpected Reactions with Anti-A/Anti-B:
Resolving Discrepancies Due to Unexpected Serum Reactions:
Genotyping:
Recommended Reading
Chapter 23. Rh Blood Group System
Antigens:
D Antigen:
Weak D:
Partial D:
C/c and E/e Antigens:
G Antigen:
V and VS Antigens:
Variation in e Antigens:
Rh-null:
D Typing Discrepancies:
RH Genotyping:
Expression:
Antibodies:
Autoantibodies:
Recommended Reading
Chapter 24. Kell and Kidd Blood Group Systems
Kell Blood Group System:
Antigens:
McLeod Phenotype:
Expression:
Antibodies:
Kidd Blood Group System:
Antigens:
Expression:
Antibodies:
Recommended Reading
Chapter 25. MNS and Duffy Blood Group Systems
MNS Blood Group System:
Antigens:
Expression:
Antibodies:
Duffy Blood Group System:
Antigens:
Expression:
Antibodies:
Recommended Reading
Chapter 26. Lewis, I and P Blood Group Systems
Lewis Blood Group System:
Antigens:
Expression:
Antibodies:
Ii Antigens:
Antigens:
Expression:
Antibodies:
P and GLOB Blood Group Systems:
Antigens:
Expression:
Antibodies:
Autoanti-P:
Recommended Reading
Chapter 27. Other Blood Group Systems, Collections and Antigens
Blood Group Systems:
Chido/Rogers Blood Group System:
Colton Blood Group System:
Cromer Blood Group System:
Diego Blood Group System:
Dombrock Blood Group System:
Gerbich Blood Group System:
Indian Blood Group System:
John Milton Hagen Blood Group System:
Knops Blood Group System:
Lutheran Blood Group System:
LW Blood Group System:
Ok Blood Group System:
Raph Blood Group System:
Scianna Blood Group System:
Yt Blood Group System:
Xg Blood Group System:
Blood Group Collections:
Cost Blood Group Collection:
Er Blood Group Collection:
High-incidence RBC Antigens:
Vel Antigen:
Lan Antigen:
Jra Antigen:
AnWj Antigen:
Sda Antigen:
Low-incidence RBC Antigens:
Chapter 28. Red Blood Cells and Related Products
Product Names:
Description:
RBC Storage Lesion:
Indications:
Signs and Symptoms of Anemia:
RBC Exchange:
As an Adjunct to Radiation Therapy:
Laboratory Values as Transfusion Triggers and Guidelines for RBC Administration:
Special RBC Products and Circumstances:
Contraindications:
Processing and Storage:
Preparation and Administration:
ABO/D Compatibility:
Quality Assurance:
Dose:
Adverse Events:
Alternatives and Future Considerations:
International Considerations:
Recommended Reading
Chapter 29. Plasma Products
Product Names:
Description:
Fresh Frozen Plasma:
Plasma Frozen within 24 hours After Phlebotomy:
Thawed Plasma:
Recovered Plasma (Plasma for Manufacture):
Source Plasma:
Cryoprecipitate-reduced Plasma:
Solvent-detergent Plasma (SD Plasma):
Indications:
Liver Disease and Transplantation:
Massive Transfusion:
Rapid Reversal of Warfarin:
Disseminated Intravascular Coagulopathy:
Plasma as a Replacement Fluid for Plasma Exchange:
Thrombotic Thrombocytopenic Purpura:
Congenital Coagulation Factor Deficiencies:
Other Multiple Coagulation Defects:
Dosage:
Compatibility:
Adverse Events:
Alternatives to Plasma Products:
International Considerations:
Recommended Reading
Chapter 30. Platelet Products
Product Names:
Description:
Indications:
Prophylactic Platelet Transfusion:
Therapeutic Platelet Transfusion:
Transfusion for Platelet Dysfunction:
Platelet Transfusion for Neonates:
Relative Contraindicated for Platelet Transfusions:
Preparation and Administration:
Whole Blood Derived:
Apheresis:
Storage:
Storage Containers:
Bacterial Testing:
TRALI Reduction Strategies:
Leukoreduction:
Irradiation:
Washing or Volume Reduction:
Aliquots:
Quality Assurance:
Dose:
Prophylactic Transfusion:
Therapeutic Transfusion:
Product Selection:
ABO Compatibility:
D Compatibility:
Adverse Events:
Alternatives and Future Considerations:
International Standards:
Buffy Coat Prepared:
Platelet Solutions:
Pathogen-reduction/-inactivation Technologies:
Quality Assurance:
Recommended Reading
Chapter 31. Cryoprecipitate
Product Names:
Description:
Indications:
Fibrinogen Replacement:
Massive Transfusion:
Fibrin Glue or Fibrin 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 Deficiency States:
Factor XIII Deficiency States:
Adverse Events:
International Standards:
Recommended Reading
Chapter 32. Granulocyte products
Description:
Indications:
Neonatal Sepsis:
Neutrophil Function Defects:
Neutropenic Patients:
Processing and Storage:
Collection:
Storage:
Patient Selection, Dose Preparation, Administration and Toxicities:
Patient Selection:
Dose:
Preparation:
Administration:
Toxicities:
Quality Assurance:
International Issues:
Recommended Reading
Chapter 33. Albumin and Related Products
Indications:
Therapeutic Plasma Exchange:
Ovarian Hyperstimulation Syndrome:
Cirrhosis with Spontaneous Bacterial Peritonitis:
Large-volume Therapeutic Paracentesis:
Nephrotic Syndrome:
Hypoalbuminemia:
Contraindications:
Adverse Effects:
Cost and Usage:
Manufacturing:
Storage:
Preparation and Administration:
Albumin Dosing:
Adult Dosing:
Pediatric Dosing:
Other Colloid Solutions:
Plasma Protein Fraction:
Dextrans:
Gelatins:
Hydroxyethylene Starch:
Recommended Reading
Chapter 34. Human Immunoglobulin Preparations
Intravenous Immune Globulin (IVIG):
Description:
Mechanism of Action:
Indications and Dose:
Organ Transplantation:
Preparation and Administration:
Adverse events:
Hyperimmune Globulin Products:
Pathophysiology:
Preparation and Administration:
Adverse Events:
Recommended Reading
Chapter 35. Rh Immune Globulin
Indications in the Prevention of Anti-D Formation:
Perinatal Administration:
D-positive Blood Product Transfusion into a D Negative Recipient:
Indications in Idiopathic Thrombocytopenia Purpura:
Preparation and Administration:
Adverse Events:
International Standards:
Recommended Reading
Chapter 36. Irradiation of Blood Products
Risk of TA-GVHD:
Indications for Irradiated Products:
Guidelines and Standards for Irradiation and Mitigation of TA-GVHD:
Universal Irradiation:
Blood Products Requiring Irradiation:
Processing and Storage:
Sources of Irradiation:
Dose:
Storage and Expiration:
Quality Assurance:
Adverse Events:
International Considerations:
Recommended Reading
Chapter 37. Leukoreduction of Blood Products
Indications for Leukoreduction:
Decreasing Incidence of Febrile Non-Hemolytic Transfusion Reactions (FNHTR):
Decreasing Incidence of HLA Alloimmunization:
Decreasing Cytomegalovirus (CMV) Transmission:
Potential Indications:
Decreasing other Human Herpesvirus Transfusion Transmitted Infections:
Prion Disease:
Controversial Indications:
Transfusion Related Immunomodulation (TRIM):
Contraindications:
Methods of Leukoreduction:
Filtration Leukoreduction:
Process Leukoreduction:
Quality Assurance:
Pre-storage versus Bedside Leukoreduction:
Universal versus Diagnosis-specific Leukoreduction:
International Differences:
Recommended Reading
Chapter 38. CMV-safe Blood Products
Description:
Indications:
Processing and Storage:
CMV Seronegative Products:
CMV Seronegative versus CMV-safe by Leukoreduction:
Quality Assurance:
Antibody Tests:
Adverse Events:
International Differences:
Recommended Reading
Chapter 39. Frozen Blood Products
Cryopreservation of RBC Products:
Cryopreservation with Glycerol:
Rejuvenation:
Thawing of Frozen RBC Product:
Refreezing of Thawed RBC Products:
Indications:
Cryopreservation of HPC Products:
Cryopreservation with DMSO:
Thawing of HPC Product:
Recommended Reading
Chapter 40. Washed Blood Products
Washing of RBC Products:
Washing of Platelet Products:
Indications:
Prevention of Recurrent Severe Allergic/Anaphylactic Transfusion Reactions:
Neonatal Alloimmune Thrombocytopenia:
Large-volume or Rapid Transfusion into Neonates and Small Children:
Irradiated RBC Products:
Patients with T-Activation:
Paroxysmal Nocturnal Hemoglobinuria:
Recommended Reading
Chapter 41. Volume-reduced Products
Red Blood Cell Products:
Methods:
Indications:
Adverse Effects:
Platelet Products:
Methods:
Indications:
Adverse Effects:
Hematopoietic Progenitor Cell Products:
Recommended Reading
Chapter 42. Neonatal and Pediatric Transfusion Medicine
Red Blood Cell Transfusions:
RBC Transfusion Considerations in Neonates:
RBC Product Selection for Neonates:
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:
Plasma Transfusions:
Plasma Product Selection:
Cryoprecipitate Transfusions:
Cryoprecipitate Product Selection:
Granulocyte Transfusions:
Granulocyte Product Selection:
Recommended Reading
Chapter 43. Perinatal Transfusion Medicine
Hemolytic Disease of the Fetus and Newborn:
Prenatal Testing:
D Positive, No Alloantibodies:
D Negative, Unsensitized to the D Antigen:
Alloantibodies Currently or Previously Detected:
Intrauterine Transfusions:
RBC Transfusions:
Platelet Transfusions:
Neonatal Testing:
Treatment of the Neonate with HDFN:
RBC Exchange Transfusion:
Recommended Reading
Chapter 44. Autoimmune Hemolytic Anemias
Clinical Manifestations:
Warm Autoimmune/Hemolytic Anemia:
Pathogenesis:
Treatment:
Blood Bank and Transfusion Management:
AIHA Associated with a Negative DAT:
Cold Agglutinin Disease:
Pathogenesis:
Treatment:
Blood Bank and Transfusion Management:
Combined Cold and Warm AIHA:
Paroxysmal Cold Hemoglobinuria:
Drug-induced Hemolytic Anemia:
Drug Adsorption (Hapten) Hypothesis:
Immune Complex Hypothesis:
Autoantibody Induction by Drugs:
Non-immunologic Protein Adsorption (Membrane Modification):
Recommended Reading
Chapter 45. Transfusion Management in Patients with Hemoglobinopathies
Sickle Cell Disease:
Pathophysiology:
Methods
Calculations:
Indications for Acute Transfusions:
Indications for Chronic Transfusions:
Controversial Indications for Transfusion:
Not Indicated for Transfusion:
RBC Product Selection:
Adverse Effects:
β-Thalassemia:
Pathophysiology:
Indications:
Management:
Adverse Effects:
Recommended Reading
Chapter 46. Transfusion of Patients Undergoing HPC and Solid-organ Transplantation
Transfusion of Patients Undergoing HPC Transplantation:
Description:
Red Blood Cell Transfusion and Product Selection:
Platelet Transfusion:
Plasma Transfusion:
Granulocyte Transfusion:
Transfusion of Patients Undergoing Solid-organ Transplantation:
Description:
ABO-incompatible Transplantation:
RBC Product Selection:
Platelet Product Selection:
Plasma Product Selection:
Recommended Reading
Chapter 47. Transfusion of HIV-positive Patients
Pathophysiology:
Anemia in HIV-positive Patients:
Thrombocytopenia in the HIV-positive Patient:
RBC Transfusion:
Indication:
RBC Product Selection:
Leukoreduction:
Irradiation:
Platelet Transfusion:
Indication:
Platelet Product Selection:
Leukoreduction and Irradiation:
Adverse Effects:
Transfusion-transmitted Diseases:
Recommended Reading
Chapter 48. Management of Patients Who Refuse Blood Transfusion
Specific Circumstances:
Trauma:
Pregnant Women and Children:
Blood Management:
Documentation of Consent or Non-consent:
Recommended Reading
Chapter 49. Platelet Transfusion Refractory Patients
Non-immune Refractoriness:
Immune Refractoriness:
Calculation of Refractoriness:
Testing:
HLA Antibody Detection:
HPA Antibody Detection:
Treatment of the Alloimmunized Patient:
HLA Antigen Based Selection:
Platelet Crossmatching:
Sibling Donors:
Bleeding, Platelet-refractory Patient:
Prevention:
Recommended Reading
Chapter 50. Massive Transfusion
Clinical Significance:
Resuscitation Approaches:
Crystalloid versus Colloid Replacement:
RBC Transfusion:
Component Therapy Based Approaches:
Massive Transfusion Protocols:
Multidisciplinary Communication:
Complications of Massive RBC Transfusion:
Recommended Reading
Chapter 51. Perioperative Blood Management
Factors Influencing the Risk of Transfusion:
Preoperative Factors:
Intraoperative Factors:
Postoperative Factors:
Blood Utilization Guidelines:
Pharmaceutical Preparations:
Desmopressin:
Antifibrinolytics:
Recombinant Factor VIIa:
Fibrin Sealant:
Autologous Blood:
Advantages:
Disadvantages:
Costs:
Preoperative Autologous Donation:
Autologous Platelet-rich Plasma:
Acute Normovolemic Hemodilution:
Intraoperative Autologous Transfusion:
Postoperative Autologous Transfusion:
Controlled Hypotension:
Recommended Reading
Chapter 52. Adverse Events and Outcomes Following Transfusion
Transfusion Reactions:
Posttransfusion Complications:
Serious Hazards of Transfusion:
Efforts to Mitigate the Leading Causes of Transfusion-associated Death:
Developing NiSHOTs:
Recommended Reading
Chapter 53. Febrile Non-hemolytic Transfusion Reactions
Incidence:
Diagnosis, Differential Diagnosis and Evaluation:
Pathophysiology:
Management:
Prevention:
Recommended Reading
Chapter 54. Allergic, Anaphylactoid and Anaphylactic Reactions
Pathophysiology:
Anti-IgA:
Antibodies to Other Normal Serum Proteins:
Components Within the Blood Product:
Latex Allergy:
Clinical Features:
Diagnosis:
Treatment:
Mild Allergic Reactions:
Severe Allergic Reactions:
Risks of Diphenydramine Administration:
Prevention:
Prophylactic Premedication in Patients without Prior History:
Prophylactic Premedication in Patients with a Prior History of Allergic Reactions:
IgA Deficiency:
Prophylaxis for Patients with IgA Deficiency and History of Anaphylactic Reactions:
Recommended Reading
Chapter 55. Acute Hemolytic Transfusion Reactions
Transfusion of Incompatible RBCs:
Incidence:
Clinical Manifestations:
Pathophysiology:
DIC, Blood Pressure Fluctuation, Shock and Renal Failure:
Diagnosis and Evaluation:
Management:
Sources of Mistransfusion:
Prevention:
Transfusion of Significant Amounts of Incompatible Plasma:
Out-of-group Platelet Transfusion:
Prevention:
Recommended Reading
Chapter 56. Delayed Hemolytic Transfusion Reactions
Incidence:
Clinical Manifestations:
Pathophysiology:
Diagnosis:
Differential Diagnosis:
Timeline of DHTR:
Management:
Prevention:
Hyperhemolytic Transfusion Reaction:
Recommended Reading
Chapter 57. Transfusion Associated Circulatory Overload
Incidence:
Clinical Manifestations:
Pathophysiology:
Diagnosis:
Differential Diagnosis:
Management:
Prevention:
Recommended Reading
Chapter 58. Transfusion Related Acute Lung Injury
Definition:
Clinical Manifestations:
Pathophysiology:
Diagnosis:
Differential Diagnosis:
Management:
Future Transfusion Considerations:
Donor/recipient Investigation:
Prevention:
Recommended Reading
Chapter 59. Septic Transfusion Reactions
Incidence:
RBC Products:
Platelet Products:
Plasma and Cryoprecipitate:
Clinical Manifestations:
Diagnosis:
Differential Diagnosis:
Treatment:
Contamination Source:
Organisms:
Prevention:
Recommended Reading
Chapter 60. Metabolic, Hypotensive and Other Acute Reactions and Complications
Metabolic Complications of Transfusion:
Pathophysiology:
Clinical Features:
Diagnosis:
Treatment:
Prevention:
Hypotensive Reactions:
Pathophysiology:
Clinical Features:
Diagnosis:
Treatment:
Prevention:
Red Eye Syndrome:
Pathophysiology:
Clinical Features:
Diagnosis:
Treatment:
Prevention:
Back Pain:
Pathophysiology:
Clinical Features:
Diagnosis:
Treatment:
Prevention:
Recommended Reading
Chapter 61. Posttransfusion Purpura
Pathophysiology:
Clinical Manifestations:
Diagnosis:
Treatment:
Prevention:
Recommended Reading
Chapter 62. Transfusion Associated Graft Versus Host Disease
Graft versus Host Disease:
Pathophysiology of TA-GVHD:
HPC Associated versus TA-GVHD:
Post-operative Erythroderma:
Diagnosis, Treatment and Prevention of TA-GVHD:
Diagnosis:
Treatment:
Prevention:
Blood Product Factors Contributing to the Risk of TA-GVHD:
Age of Blood:
Leukocyte Dose:
Blood Products:
Patients at Increased Risk for TA-GVHD:
Congenital Immunodeficiency Patients:
Allogeneic and Autologous HPC Recipients:
Patients with Hematologic Malignancies:
Recipients of Fludarabine and Other Purine Analogues as Well as Other Drugs/antibodies that Affect T-lymphocyte Number or Function:
Fetuses and Neonates:
Patients with Aplastic Anemia:
Patients Receiving Chemotherapy and Immunotherapy:
Solid-organ Transplantation Recipients:
Human Immunodeficiency virus and Adult Immunodeficiency Syndrome Patients:
Cardiovascular Surgery Patients:
Immunocompetent Patients:
Recommended Reading
Chapter 63. Microchimerism
Pathophysiology of TA-MC:
Normal Clearance of Transfused Lymphocytes:
Transfusion-associated Microchimerism:
Clinical Elements of TA-MC:
Diagnosis:
Testing Limitations:
Prevention:
Recommended Reading
Chapter 64. Transfusion Related Immunomodulation
Accepted TRIM Effects:
Solid Organ Transplantation:
Reduction in the Likelihood of Spontaneous Abortion:
Debated TRIM Effects:
Cancer, Infection and Autoimmunity:
Proposed Mechanisms of TRIM:
Recommended Reading
Chapter 65. Iron Overload
Pathophysiology:
Clinical Manifestations:
Diagnosis:
Management:
Recommended Reading
Chapter 66. Transfusion Transmitted Diseases
Hepatitis Viruses:
Hepatitis A:
Hepatitis B:
Hepatitis D:
Hepatitis C:
Hepatitis E:
Hepatitis G:
TTV and SEN-V:
Retroviruses:
Human Immunodeficiency Virus:
Human T-cell Lymphotropic Virus:
Herpesviruses:
Cytomegalovirus:
Epstein Barr Virus:
HHV-8:
Other Viruses:
Parvovirus B19:
West Nile Virus:
Protozoa:
Plasmodium spp. (Malaria):
Trypanosoma Cruzi (Chagas' Disease):
Toxoplasma Gondii (Toxoplasmosis):
Babesia Microti/Divergens (Babesiosis):
Leishmania spp. (Leishmaniasis):
Prions:
Transmissible Spongiform Encephalopathies (Creutzfeldt-Jakob Disease):
Other Emerging Infections:
Recommended Reading
Chapter 67. Overview of Therapeutic Apheresis
Methods:
Volumes Exchanged:
Calculation of Total Blood Volume, Total RBC Volume, and Total Plasma Volume:
Total Extracorporeal Volume and Total RBC Extracorporeal Volume:
Replacement Solutions:
Vascular Access:
Anticoagulation:
Citrate:
Heparin:
Adverse Events:
Citrate Toxicity:
Allergic Reactions:
ASFA Indication Categories:
Category I:
Category II:
Category III:
Category IV:
Evaluation of a New Patient for The Initiation of TA:
Rationale:
Impact:
Technical Issues:
Therapeutic Plan:
Clinical and/or Laboratory End-points:
Timing and Location:
Recommended Reading
Chapter 68. Therapeutic Plasma Exchange
Pathophysiology:
Methods:
Volume Exchanged:
Timing and Frequency:
Replacement Fluids:
Indications:
ABO-incompatible Hematopoietic Progenitor Cell Transplantation (Category II):
ABO-incompatible Solid-organ Transplantation (Category II for Kidney and Heart [Infants Only] and Category III for Liver):
Acute Disseminated Encephalomyelitis (Category III):
Acute Liver Failure (Category III):
Acute Inflammatory Demyelinating Polyneuropathy (AIDP; Guillain-Barré Syndrome) (Category I):
Amyloidosis, Systemic (Category IV):
Amyotrophic Lateral Sclerosis (ALS) (Category IV):
ANCA-associated Rapidly Progressive Glomerulonephritis (Wegener’s Granulomatosis) (Category II):
Anti-glomerular Basement Membrane Glomerulonephritis (Anti-GBM GN; Goodpasture’s Syndrome) (Category I):
Aplastic Anemia (AA); Pure Red Cell Aplasia (PRCA) (Category III):
Autoimmune Hemolytic Anemia (AIHA): Warm Autoimmune Hemolytic Anemia (WAIHA); Cold Agglutinin Disease (CAD) (Category III):
Catastrophic Antiphospholipid Syndrome (CAPS) (Category III):
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) (Category I):
Coagulation Factor Inhibitors (Category III):
Cryoglobulinemia (Category I):
Dermatomyositis or Polymyositis (Category IV):
Familial Hypercholesterolemia (FH) (Category II):
Focal Segmental Glomerulosclerosis (FSGS) (Category III for Primary and Recurrent Disease):
Heart Transplant Rejection (Category III):
Hemolytic Uremic Syndrome (HUS), Thrombotic Microangiopathy (TMA), and Transplanted Associated Microangiopathy (Category III for Familial HUS, TMA, and TAM and Category IV for Diarrhea-positive Pediatric HUS):
Hypertriglyceridemic Pancreatitis (Category III):
Hyperviscosity in Monoclonal Gammopathies (Category I):
Idiopathic Thrombocytopenic Purpura (ITP) (Category IV):
Inclusion Body Myositis (IBM) (Category IV):
Lambert-Eaton Myasthenic Syndrome (LEMS) (Category II):
Multiple Sclerosis (Category II for Acute CNS Inflammatory Demyelinating Disease and Category III for Devic’s Syndrome and Chronic Progressive MS):
Myasthenia Gravis (MG) (Category I):
Myeloma/Acute Renal Failure (Category III):
Overdose and Poisoning (Category II for Mushroom Poisoning and Category III for other Compounds):
Paraneoplastic Neurologic Syndromes (Category III):
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and Sydenham’s Chorea (SC) (Category I for Severe Exacerbation):
Pemphigus Vulgaris (Category III):
Phytanic Acid Storage Disease (Refsum’s Disease) (Category II):
Paraproteinemic Polyneuropathies (Category 1 for Demyelinating Poly-neuropathy with IgG/IgA, Category II for Polyneuropathy with IgM (±Waldenström’s), and Category III for Multiple Myeloma with Polyneuropathy):
Posttransfusion Purpura (Category III):
Polyneuropathy, Organomegaly, Endocrinopathy, M Protein and Skin Changes (POEMS) Syndrome (Category IV):
Psoriasis (Category IV):
Rapidly Progressive Glomerulonephritis (RPGN) (Category III):
Rassmussen’s Encephalitis (Category II):
RBC Alloimmunization in Pregnancy (Category II):
Renal Transplantation/Antibody-mediated Rejection (AMR) and HLA Desensitization (Category II for AMR and Desensitization):
Rheumatoid Arthritis (RA) (Category IV):
Scleroderma/Progressive Systemic Sclerosis (Category III):
Schizophrenia (Category IV):
Sepsis (Category III):
Stiff-person Syndrome (Category III):
Systemic Lupus Erythematosus (SLE) (Category III Except Lupus Nephritis, which is Category IV):
Thrombotic Thrombocytopenic Purpura (TTP) (Category I):
Thyrotoxicosis (Category III):
Adverse Effects:
Drug Removal During Apheresis:
Dilutional Coagulopathy:
Citrate Toxicity:
Allergic Reactions:
ACE Inhibitor Reactions:
Recommended Reading
Chapter 69. Therapeutic Erythrocytapheresis
Indications:
Sickle Cell Disease (ASFA Category I for Life- and Organ-threatening Complications, Category II for Primary and Secondary Stroke Prophylaxis and Prevention of Iron Overload):
Malaria (ASFA Category II for Severe Disease):
Babesiosis (ASFA Category II for Severe Cases):
Erythrocytosis and Polycythemia Vera (ASFA Category II for Symptomatic Erythrocytosis):
Volume Exchanged:
Replacement Fluids:
End Hematocrit:
Adverse Effects:
Recommended Reading
Chapter 70. Therapeutic Thrombocytapheresis
Indications:
Thrombocytosis (ASFA Category II for Symptomatic Thrombocytosis and Category III for Prophylactic or Secondary Thrombocytosis):
Volume Exchanged:
Recommended Reading
Chapter 71. Therapeutic Leukapheresis
Indications:
Hyperleukocytosis (ASFA Category I for Symptomatic Leukostasis and Category III for Prophylaxis):
Volume Exchanged:
Timing:
Replacement Fluids:
Recommended Reading
Chapter 72. Extracorporeal Photopheresis
Pathophysiology:
Methods:
Indications:
Cutaneous T-cell Lymphoma (CTCL) (FDA Approved; ASFA Category I for Erythrodermic CTCL; Category IV for Non-erythrodermic CTCL):
Graft-versus-host Disease (GVHD) (Off-label Use; ASFA Category II for Acute and Chronic Skin GVHD; Category III for Non-skin Acute and Chronic GVHD):
Heart Transplant Rejection (Off-label Use; Asfa Category I for Prophylaxis for Rejection; Category II for Treatment of Rejection):
Lung Transplant Rejection (Off-label Use; ASFA Category III):
Pemphigus Vulgaris (Off-label Use; ASFA Category III):
Scleroderma/Progressive Systemic Sclerosis (Off-label Use; ASFA Category IV):
Adverse Effects:
Recommended Reading
Chapter 73. LDL Pheresis
Indications:
Familial Hypercholesterolemia (ASFA Category I for Homozygotes and Category II for Heterozygotes):
Methods:
Adverse Effects:
Recommended Reading
Chapter 74. Immunoadsorption
Indications:
Coagulation Factor Inhibitors (ASFA Category III):
Idiopathic Thrombocytopenic Purpura (ITP) (ASFA Category II for Refractory Disease):
Rheumatoid Arthritis (RA), Refractory (ASFA category II):
Methods:
Adverse Effects:
Recommended Reading
Chapter 75. Therapeutic Phlebotomy
Indications:
Hereditary Hemochromatosis:
Secondary Hemochromatosis:
Polycythemia Vera:
Secondary Polycythemia:
Methods:
Adverse Effects:
Recommended Reading
Chapter 76. HPC Products
HPC, Apheresis:
HPC, Marrow:
HPC, Cord Blood:
Cellular Content:
Indications:
Collection:
Collection of HPC, Apheresis:
Harvesting HPC, Marrow:
HPC, Cord Blood:
Processing:
Processing of ABO-incompatible Products:
Special Processing:
Storage:
Preparation and Infusion:
Adverse Events:
Quality Assurance:
Dose:
Donor Lymphocyte Infusions:
Indications:
Dosage:
Collection:
Processing and Storage:
Preparation and Infusion:
Quality Assurance:
Adverse Events:
Recommended Reading
Chapter 77. Tissue Banking in the Hospital Setting
Tissue Suppliers and Hospital Tissue Services:
Tissues Transplanted at Hospitals:
Regulatory Agencies and Tissue Banking:
Decentralized Tissue Services in Hospitals:
Centralized Tissue Services in Hospitals:
Recommended Reading
II. Coagulation
Chapter 78. Overview of the Coagulation System
Platelet/Blood Vessel Interaction:
Role of the Blood Vessel:
Endothelial Cells:
The Role of Platelets in Blood Vessel Interaction:
Platelet Structure:
Platelet Adhesion:
Shape Change and Secretion:
Platelet Aggregation:
Platelet’s Role in Coagulation:
Clot Retraction and Remodeling:
Formation of Thrombin:
Recommended Reading
Chapter 79. Approach to the Bleeding Patient
History:
Mucosal Bleeding:
Menorrhagia:
Other Bleeding History:
Bleeding in Infancy:
Medications:
Factor Deficiency versus Platelet/Vessel Interaction Bleeding:
Physical Examination:
Newborn Bleeding:
Surgical versus Systemic Bleeding:
Summary Comments:
Laboratory Evaluation:
PT, PTT and Mixing Studies:
PFA and Thrombin Time:
Vascular Bleeding:
Pre-analytical Errors and Pitfalls to Coagulation Testing:
Overview of Coagulation Testing:
Recommended Reading
Chapter 80. Congenital Thrombocytopenia
Differential Diagnosis:
Management:
Congenital Thrombocytopenias:
Thrombocytopenia with Small Platelets:
Thrombocytopenia with Normal Platelet Size:
Thrombocytopenia with Large/Giant Platelets:
Recommended Reading
Chapter 81. Neonatal Alloimmune Thrombocytopenia
Pathophysiology:
Clinical Manifestations:
Diagnosis:
Differential Diagnosis:
Management:
Postnatal Management:
Antenatal Management:
Delivery:
The Future:
Recommended Reading
Chapter 82. Acquired Neonatal Thrombocytopenia
Pathophysiology:
Decreased Production:
Increased Destruction:
Clinical Manifestations:
Diagnosis:
Differential Diagnosis:
Management:
Recommended Reading
Chapter 83. Bernard-Soulier Syndrome and Other GPIb-IX-V 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-V):
Recommended Reading
Chapter 84. Glanzmann Thrombasthenia
Pathophysiology:
Variant GT:
Diagnosis:
Management:
Recommended Reading
Chapter 85. Platelet Storage-granule Defects
Diagnosis:
Management:
Hermansky-Pudlak Syndrome:
Chediak-Higashi Syndrome:
Gray platelet syndrome:
White Platelet Syndrome:
Other Granule Defects:
Recommended Reading
Chapter 86. Failure to Release and Aspirin-like Defects
Pathophysiology:
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:
Recommended Reading
Chapter 87. Acute (Childhood) Immune Thrombocytopenic Purpura
Pathophysiology:
Clinical Manifestations:
Diagnosis:
Differential Diagnosis:
Management:
Recommended Reading
Chapter 88. Chronic Immune Thrombocytopenic Purpura
Pathophysiology:
Clinical Manifestations:
Diagnosis:
Differential Diagnosis:
Management:
Initial Management:
Relapse:
Refractory ITP:
Recommended Reading
Chapter 89. Drug-induced Thrombocytopenia
Pathology:
Decreased Production:
Increased Destruction:
Clinical Manifestations:
Diagnosis:
Differential Diagnosis:
Management:
Recommended Reading
Chapter 90. Heparin-induced Thrombocytopenia
Pathophysiology:
Clinical Manifestations:
Thrombocytopenia:
Thrombosis and Other Sequelae:
Diagnosis:
Laboratory Testing:
Differential Diagnosis:
Management:
Platelet Transfusions:
Cardiac Surgery:
Patient Education:
Recommended Reading
Chapter 91. Autoimmune Lymphoproliferative Syndrome
Pathophysiology:
Clinical Manifestations:
Diagnosis:
Differential Diagnosis:
Management:
Recommended Reading
Chapter 92. Hemolytic Uremic Syndrome
Pathophysiology:
Diarrhea-associated HUS:
Atypical HUS:
Clinical Manifestation and Laboratory Features:
Diagnosis:
CBC and Coagulation Markers:
Renal Function and Other Complications:
Differential Diagnosis:
Management/Prognosis:
Diarrhea-associated HUS:
Atypical HUS:
Recommended Reading
Chapter 93. Thrombotic Thrombocytopenic Purpura
Pathophysiology:
Epidemiology:
Clinical Manifestations:
Diagnosis:
Differential Diagnosis:
Management:
Refractory Disease:
Exacerbation:
Relapse:
Familial TTP:
Recommended Reading
Chapter 94. Antiphospholipid Antibody Syndrome
Pathophysiology:
Clinical Manifestations:
Diagnosis:
Management:
Recommended Reading
Chapter 95. von Willebrand Disease
Pathophysiology:
Classification:
Type 1 VWD:
Type 2 VWD:
Type 3 VWD:
Clinical Manifestations:
Diagnosis:
Differential Diagnosis:
Management:
Minor Bleeding:
Major or Perioperative Bleeding:
Recommended Reading
Chapter 96. Hemophilia A
Pathophysiology:
Clinical Manifestations:
Diagnosis:
Differential Diagnosis:
Management:
Factor Concentrates:
Prophylaxis:
Desmopressin:
Complications:
Infectious complications:
Inhibitors:
Joint Disease:
Recommended Reading
Chapter 97. Hemophilia B
Pathophysiology:
Clinical Manifestations:
Diagnosis:
Differential Diagnosis:
Management:
Complications:
Anaphylactoid Reactions and Inhibitors:
Nephrotic Syndrome:
Joint Disease:
Recommended Reading
Chapter 98. Congenital Disorders of Fibrinogen
Pathophysiology:
Role in Coagulation:
Genetics:
Clinical Manifestations:
Diagnosis:
Differential Diagnosis:
Management:
Recommended Reading
Chapter 99. Factor XIII, α2-Antiplasmin and Plasminogen Activator Inhibitor-1 Deficiencies
Pathophysiology:
Role in Coagulation:
Genetics:
Clinical Manifestations:
FXIII Deficiency:
α2-AP Deficiency:
PAI-1 Deficiency:
Diagnosis:
Differential Diagnosis:
Management:
Recommended Reading
Chapter 100. Factor XI Deficiency
Pathophysiology:
Biochemistry:
Genetics:
Clinical Manifestations:
Homozygous or Compound Heterozygous FXI Deficiency:
Heterozygous FXI Deficiency:
Diagnosis:
Laboratory Diagnosis:
Differential Diagnosis:
Management:
Recommended Reading
Chapter 101. Factor VII Deficiency
Pathophysiology:
Diagnosis:
Differential Diagnosis:
Management:
Recommended Reading
Chapter 102. Factor II, Factor V and Factor X Deficiencies
Pathophysiology:
Role in Coagulation:
Genetics:
Diagnosis:
Differential Diagnosis:
Management:
Recommended Reading
Chapter 103. Bleeding Disorders in Pregnancy
Congenital Disorders:
von Willebrand Disease:
Carriers of Hemophilia A or B:
Factor XI Deficiency:
Platelet Function Defects:
Other Inherited Defects:
Prenatal Counseling and Delivery of Fetus with a Potential Bleeding Disorder:
Acquired Disorders:
Acquired FVIII Inhibitors:
Thrombocytopenia:
Recommended Reading
Chapter 104. Vascular Bleeding Disorders
Hereditary Vascular Malformations:
Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Disease):
Giant Cavernous Hemangiomata and Kasabach-Merritt Syndrome:
Hereditary Connective Tissue Disorders:
Ehlers-Danlos Syndrome:
Pseudoxanthoma Elasticum:
Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes Syndrome:
Acquired Vascular Disorders:
Purpura Simplex (Idiopathic Purpura):
Senile Purpura:
Purpura Due to Infections:
Scurvy:
Henoch-Schönlein Purpura:
Recommended Reading
Chapter 105. Bleeding Risks with Liver Disease
Pathophysiology:
Decreased Synthesis of Clotting Factors:
Vitamin K Deficiency:
Thrombocytopenia:
Platelet Dysfunction:
Disseminated Intravascular Coagulopathy:
Systemic Fibrinolysis:
Abnormal Fibrinogen (Dysfibrinogenmia):
Clinical Manifestations:
Diagnosis:
Differential Diagnosis:
Summary of Laboratory Differentiation in Hepatic Failure:
Management:
Conventional Management:
Difficult Bleeding Management:
Recommended Reading
Chapter 106. Bleeding Risks with Vitamin K Deficiency
Pathophysiology:
Clinical Manifestation:
Diagnosis:
Management:
Recommended Reading
Chapter 107. Bleeding Risks with Cardiac Disease
Pathophysiology:
Cardiopulmonary by Pass:
Cyanotic Heart Disease:
Non-cyanotic Heart Disease/Valvular Heart Disease:
Clinical Manifestations:
Diagnosis and Differential Diagnosis of Bleeding Associated with CPB:
Initial Bleeding Assessment Associated with CPB:
Heparin Reversal:
Screening Laboratory in CPB Bleeding Assessment:
Management:
Desmopressin:
Antifibrinolytic Therapy:
Anticoagulation Therapy:
Therapy for Inhibitors to Bovine Thrombin:
Recommended Reading
Chapter 108. Bleeding Risks with Renal Disease
Pathophysiology:
Platelet Dysfunction:
Anemia-associated Bleeding:
Thrombocytopenia:
Bleeding Secondary to Medications:
Hypofibrinolysis:
Nephrotic Syndrome:
Clinical Manifestations:
Diagnosis:
Differential Diagnosis:
Management:
Recommended Reading
Chapter 109. Bleeding Risks in Cancer
Clinical Manifestations:
Platelet Disorders and Thrombocytopenia:
Coagulation Abnormalities:
Diagnosis:
Management:
Recommended Reading
Chapter 110. Disseminated Intravascular Coagulopathy
Pathophysiology:
Clinical Manifestations:
Diagnosis:
Differential Diagnosis:
Management:
Platelet and Plasma Support:
Anticoagulant Pathway Therapy:
Anticoagulants:
Antifibrinolytic Therapy:
Recommended Reading
Chapter 111. Acquired Coagulation Factor Inhibitors
Inhibitors of FVIII:
Pathophysiology:
Clinical Manifestations:
Diagnosis:
Management:
Inhibitors of VWF:
Pathophysiology:
Clinical Manifestations:
Diagnosis:
Management:
Inhibitors of FV:
Inhibitors of Prothrombin and Thrombin:
Recommended Reading
Chapter 112. Introduction to Coagulation Testing
Analysis of Proteins Involved in Coagulation:
Measurement of Activity:
Measurement of Protein:
Measurement of Gene Sequence:
Analysis of Cellular Biology in Coagulation:
Analysis of Therapeutic Interventions:
Integration of Coagulation Labs with Patient Care:
Chapter 113. Prothrombin Time and Activated Partial Thromboplastin Time
Prothrombin Time:
Indications:
Method:
Sources of Error:
International Standards:
Activated Partial Thromboplastin Time:
Indications:
Method:
Sources of Error:
Interpretation of PT and PTT Tests:
Prolonged PTT with Normal PT:
Prolonged PT with a Normal PTT:
Prolongation of the PT and PTT:
Shortening of the PT and PTT:
Chapter 114. Platelet Count
Methods:
Electronic Impedance Aperture:
Optical and Flow-cytometry Based Methods:
Sources of Error:
Mistakenly Counting a Small Particle that is not a Platelet:
Mistakenly Missing a Large Platelet:
Platelet Clustering or Aggregation (Pseudothrombocytopenia):
Recommended Reading
Chapter 115. Global Tests of Primary Hemostasis
Bleeding Time:
Test Performance:
Sources of Error:
Quality Assurance:
Platelet Function Analyzer:
Test Performance:
Sources of Error:
Quality Assurance:
Recommended Reading
Chapter 116. Platelet Aggregation Studies
Platelet Aggregation by Light-transmission Aggregometry (LTA):
Platelet Aggregation by Whole Blood Aggregometry (WBA):
Platelet Adenosine Triphosphate (ATP) Release:
Interpretation of Results from LTA, WBA and ATP Release:
Recommended Reading
Chapter 117. Laboratory Diagnosis of Genetic Platelet Function Defects
Platelet Aggregation Studies:
Platelet Function Analyzer:
Electron Microscopy:
DNA Sequence Analysis:
Interpretation of Results Based Upon Combined Application of the Above Lab Tests:
Glanzmann Thrombasthenia:
Storage Pool Disorders:
Alpha Granule Disorders:
Defects Detected using Ristocetin:
Scott Syndrome:
Recommended Reading
Chapter 118. Laboratory Diagnosis of Acquired Platelet Function Defects
Anemia:
Myeloproliferative Disorders:
Hepatic Disease:
Gammopathies:
Autoimmunity to Platelet Proteins:
Disseminated Intravascular Coagulopathy:
Extracorporeal Membrane Oxygenation:
Recommended Reading
Chapter 119. Laboratory Diagnosis of Immune Thrombocytopenic Purpura
Methods for Platelet Antibody Testing:
Flow Cytometry:
Monoclonal Antibody Specific Immobilization of Platelet Antigen:
Modified Antigen Capture ELISA and Immunobead Assays:
Enzyme-linked Immunosorbent Assays:
Platelet Antibody Testing in Other Diseases:
Recommended Reading
Chapter 120. ADAMTS13 Testing
ADAMTS13 Activity:
Methods:
Test Performance:
Interpretation:
ADAMTS13 Inhibitor:
Methods:
Interpretation:
Recommended Reading
Chapter 121. Laboratory Diagnosis of Heparin-induced Thrombocytopenia
Laboratory Testing for HIT Antibodies:
Antigen Assays:
Solid Phase Enzyme Immunoassays:
Fluid Phase Enzyme Immunoassays:
Rapid Immunoassays:
Potential Sources of Error:
Interpretation of Antigen Assays:
Platelet Activation (Functional) Assays:
Platelet Aggregation Test:
Serotonin Release Assay:
Heparin-induced Platelet Activation Test:
Interpretation of Functional Platelet Assays:
Other Methodologies:
Recommended Reading
Chapter 122. Molecular Biology of von Willebrand Disease
DNA Sequence Analysis:
Recommended Reading
Chapter 123. Laboratory Diagnosis of Inherited von Willebrand Disease
Ristocetin Cofactor:
VWF Antigen:
Factor VIII Coagulant Activity:
Collagen Binding Assay:
Ristocetin-induced Platelet Aggregation:
VWF Multimers:
VWF Inhibitor:
VWF Binding to Platelets:
Factor VIII Binding to VWF:
DNA Sequencing:
Diagnosis of VWD Types:
Type 1 VWD:
Type 2 VWD:
Type 3 VWD:
Platelet-type or Pseudo-VWD:
Recommended Reading
Chapter 124. Laboratory Diagnosis of Acquired von Willebrand Syndrome
Recommended Reading
Chapter 125. Laboratory Assessment of Treatment of von Willebrand Disease
Treatment Modalities:
DDAVP:
VWF Replacement:
Adjunctive Therapies:
Recommended Reading
Chapter 126. Coagulation Factor Testing
Methods:
Factor VIII Activity:
Factor VIII Antigen:
Factor IX Activity:
FIX Antigen:
FXI and FXII Activities:
FII, FV, FVII and FX Activities:
FXIII:
Test Performance:
Sources of Error:
Quality Assurance:
International Standards:
Recommended Reading
Chapter 127. Mixing Studies
Method:
Interpretation:
Test Performance:
Sources of Error:
Heparin Contamination:
Weak Inhibitors:
Quality Assurance:
Recommended Reading
Chapter 128. Specific Factor Inhibitor Testing
Methods:
Issues Surrounding Laboratory Detection of Inhibitors:
FVIII Inhibitors:
Factor IX Inhibitors:
Factor XI Inhibitors:
Factors V, VII, X and XIII Inhibitors:
von Willebrand Factor Inhibitors:
Sources of Error:
False Positive:
False Negative:
Recommended Reading
Chapter 129. Laboratory Diagnosis of Dysfibrinogenemia and Afibrinogenemia
Description, Methods and Indications:
Fibrinogen Assay Measurements:
Assessment of Hypofibrinogenemia and Afibrinogenemia:
Assessment for Dysfibrinogenemia:
Sources of Error:
Fibrinogen Detection:
Dysfibrinogen Detection:
Genetic Testing for Fibrinogen Abnormalities:
Recommended Reading
Chapter 130. Laboratory Assessment of Fibrinolysis
Laboratory Testing of Fibrinolysis:
Euglobulin Lysis Time:
Alpha 2 Antiplasmin:
Plasminogen Activator Inhibitor 1:
Tissue Plasminogen Activator:
Thrombin Activatable Fibrinolysis Inhibitor:
Fibrinogen:
Fibrin Degradation Products:
Sources of Error:
Recommended Reading
Chapter 131. General Overview of the Hypercoaguable State
Pathophysiology:
Blood Stasis:
Vessel Wall Injury:
Hypercoaguability:
Specific Perturbations Leading to Hypercoaguability:
Increased Coagulation Factors:
Antithrombin System:
Activated Protein C and Protein S System:
Tissue Factor Pathway Inhibitor:
Fibrinolytic System:
Recommended Reading
Chapter 132. Antithrombin Testing
AT Activity:
Test Interpretation:
Sources of Error:
AT Antigen:
Test Interpretation:
Recommended Reading
Chapter 133. Proteins C, S and Z Testing
Protein C and Protein S:
Diagnosis of Clinically Significant Protein C and/or Protein S Defects:
Protein Z:
Chapter 134. Activated Protein C Resistance and Factor V Leiden Testing
Activated Protein C Resistance:
Methods:
Test Interpretation:
Test Performance:
Sources of Error:
Factor V Leiden:
Methods:
Test Interpretation:
Sources of Error:
Recommended Reading
Chapter 135. Prothrombin Gene Mutation Testing
Prothrombin Gene Mutation Assay:
Methods:
Test Interpretation:
Sources of Error:
Recommended Reading
Chapter 136. Laboratory Diagnosis of Hyperhomocysteinemia
Plasma Homocysteine Level:
Methods:
Sources of Error:
MTHFR Mutation:
Methods:
Test Interpretation:
Sources of Error:
Recommended Reading
Chapter 137. Laboratory Diagnosis of Lupus Anticoagulant and Antiphospholipid Antibodies
Diagnosis:
Methods and Interpretation:
Lupus Anticoagulant:
PTT Sensitive to LA:
Dilute Russell’s Viper Venom Test:
Textarin/ecarin Time:
Dilute Prothrombin Diagnostic Assay:
Kaolin Clotting Time:
Antiphospholipid Antibodies:
Anticardiolipin Antibodies:
Anti-β2-glycoprotein I Antibodies:
Recommended Reading
Chapter 138. Lipoprotein (a) Testing
Laboratory Test:
Sources of Error:
Recommended Reading
Chapter 139. Laboratory Diagnosis of Factor Level Abnormalities Associated with Thrombosis
Association of Factor Level Abnormalities with Thrombosis:
Recommendations for Testing Individual Factors:
Current and Future Applications:
Recommended Reading
Chapter 140. Laboratory Management of DIC
Laboratory Diagnosis of DIC:
Monitoring of a Bleeding Patient in DIC:
Prothrombin Time, Partial Thromboplastin Time, and Fibrinogen:
Fibrin Degradation Products and D-dimer:
Thrombocytopenia:
Monitoring of a Thrombotic Patient in DIC:
Unique Laboratory Findings Associated with Certain Conditions of DIC:
Compensated DIC:
Early DIC with Sepsis and Hypoxia:
Excessive Fibrinolysis:
Recommended Reading
Chapter 141. Laboratory Support for Heparin Monitoring
PTT:
Interpretation:
Special Considerations and Sources of Error in Heparin Monitoring by PTT:
Lack of Specificity for Heparin Effects:
Difficulty in Standardization:
Dynamic Range of the PTT:
Chromogenic Anti-Xa Activity Assay:
Interpretation:
Comparison of the PTT and Anti-Xa Activity Assay for Monitoring Heparin Therapy:
PTT and Anti-Xa to Monitor Heparin Resistance:
Recommended Reading
Chapter 142. Laboratory Support for Warfarin Monitoring
PT:
Interpretation:
Special Considerations and Sources of Error and Warfarin Monitoring by PT:
Abnormal Warfarin Responsiveness:
Genetic Factors:
Environmental and Drug Interactions:
Recommended Reading
Chapter 143. Prothrombin Complex Concentrates
Products:
Description:
Indications:
Storage and Stability:
Dosage:
Adverse Reactions/Precautions:
Recommended Reading
Chapter 144. von Willebrand Factor Concentrates
Indications:
Storage and Stability:
Dosing:
Adverse Reactions of FVIII/VWF Containing Products:
Recommended Reading
Chapter 145. Factor VIII Concentrates
Factor VII Products:
Factor VIII Purified from Donors:
Recombinant FVIII Products:
Indications, Dosing and Administration:
Processing and Storage:
FVIII Dosing and Administration:
Complications of FVIII Therapy:
Inhibitor Development:
Infection:
Allergic Reactions:
Recommended Reading
Chapter 146. Factor IX Concentrates
Factor IX Products:
FIX Purified from Donor Plasma:
Recombinant Factor IX:
Prothrombin Complex Concentrates:
Indications, Dosing and Administration:
Complications of FIX Therapy:
Inhibitor Development:
Infection:
Allergic Reactions:
Recommended Reading
Chapter 147. Factor VII Concentrates
Manufacturing:
Pathophysiology:
Storage and Stability:
Dosage:
Adverse Reactions/Precautions:
Recommended Reading
Chapter 148. Antithrombin Concentrates
Description:
Indications:
Hereditary AT Deficiency:
Acquired AT Deficiency:
Disseminated Intravascular Coagulopathy:
Heparin Resistance:
Dosing/Administration and Stability:
Adverse Reactions/Precautions:
Recommended Reading
Chapter 149. Protein C Concentrates
Indications:
Ceprotin:
Xigris:
Dosage and Administration:
Ceprotin:
Xigris:
Storage and Stability:
Ceprotin:
Xigris:
Adverse Reactions:
Ceprotin:
Xigris:
Recommended Reading
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About the Editors
Christopher D. Hillyer, MD, is the Emory Distinguished Service Professor of Pathology, and atenured professor in the Department of Pathology and Laboratory Medicine, Emory University School of Medicine. In these capacities, he serves 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 chief editor of three textbooks in transfusion medicine, author of over 120 articles pertaining to transfusion, human immunodeficiency virus (HIV), cytokines, and herpes viruses, most notably Cytomegalovirus (CMV), as well as more than 25 book chapters. Nationally recognized as an expert in hematology and blood banking, and transfusion medicine, Dr. Hillyer also is a past-president, board of directors of AABB (formerly known as the American Association of Blood Banks) and a trustee of the National Blood Foundation (NBF). Dr. Hillyer has been awarded many million dollars in research funding from the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), NBF and other agencies. He is an associate editor of the journal Transfusion and serves on several other editorial boards including the journal Blood. Dr. Hillyer was recently recognized as a Healthcare Hero for his work in Africa and is a recipient of the Tiffany Award from the American Red Cross where he also serves as a medical director. Dr. Hillyer is board certified in four specialty areas including transfusion medicine, hematology, medical oncology and internal medicine. He received his BS from Trinity College (1980), and his MD from the University of Rochester School of Medicine (1984), with postgraduate training and fellowships in hematology-oncology, transfusion medicine and bone marrow transplantation at Tufts-New England Medical Center in Boston.
Beth H. Shaz, MD, is an associate professor in the Department of Pathology and Laboratory Medicine, Emory University School of Medicine, and serves as director of the blood bank at Grady Memorial Hospital and co-director of clinical research at the Center for Transfusion and Cellular Therapy. Prior to moving to Emory she was the assistant medical director of the Transfusion Services and medical director of the Transfusion and Apheresis Unit at Beth Israel Deaconess Medical Center. She has written many articles and book chapters pertaining to transfusion, cellular therapy, and therapeutic apheresis. Nationally, she is chair of the Clinical Applications Committee of the American Society for Apheresis, which has recently published new and evidence-based guidelines for the use of therapeutic apheresis. In addition, she is the chair of the Transfusion Services Accreditation Program Unit and the Blood Banking/ Transfusion Medicine Fellowship Program Directors Subsection of the AABB. Dr. Shaz is board certified in transfusion medicine, clinical and anatomic pathology. She received her BS from Cornell University and her MD from the University of Michigan School of Medicine. Her postgraduate training includes a general surgery internship at Georgetown University, and residency in clinical and anatomic pathology and fellowship in transfusion medicine at Beth Israel Deaconess Medical Center, a major teaching hospital of Harvard Medical School in Boston.
James C. Zimring, MD, PhD, is an associate professor in the Department of Pathology and Laboratory Medicine, Emory University School of Medicine, and serves as the assistant director of the special hemostasis laboratory at Emory University Hospital. Dr. Zimring oversees the laboratory diagnosis of patients with disorders in thrombosis and hemostasis. In addition, Dr. Zimring has an active NIH funded research program studying the immunology of transfusion and bone marrow transplantation. Dr. Zimring is a recent recipient of the David B. Pall award for advances in transfusion medicine, and frequently presents original research in the field of transfusion at national and international meetings. He is on the editorial board of the journal Transfusion and serves as a reviewer for additional journals in the fields of transfusion and coagulation. Dr. Zimring has authored several book chapters in the fields of transfusion, coagulation and molecular pathology. He is board certified in Clinical Pathology and received a BS in Chemistry, PhD in Immunology, and an MD all from Emory University.
Thomas C. Abshire, MD, is a professor in the Department of Pediatrics Emory University School of Medicine, and the director of the Comprehensive Hemostasis Program, Emory University and Children’s Healthcare of Atlanta. He also serves as the Pediatric Hematology/Oncology Fellowship Program Director at Emory and Children’s. Prior to joining the faculty at Emory University, Dr. Abshire completed a career in the United States Air Force with an emphasis as a clinician-educator, where he was the recipient of several medical student and housestaff teaching awards. Dr. Abshire’s research interest is in evaluation of mild bleeding disorders and therapeutic intervention in hemophilia, von Willebrand disease and thrombosis. He has published over 60 peer-reviewed manuscripts, review articles or editorials and is a frequent invited speaker at national and international meetings. He also serves on the Steering Committee of the International Immune Tolerance Study and recently was a member on the CDC Uniform Data Collection Committee. He has received research funding from the NIH, CDC, and several non profit organizations and pharmaceutical companies. Dr. Abshire is a past-president of the Hemophilia and Thrombosis Research Society. Dr. Abshire is a distinguished graduate of the US Air Force Academy. He attended medical school at Tulane University, fulfilled his pediatric residency training at David Grant USAF Medical Center and completed pediatric hematology/oncology fellowship training at the University of Colorado Health Science Center.
Contributors
THOMAS C. ABSHIRE, MD
Professor, Department of Pediatrics, Emory University School of Medicine
Director’s Chair in Hemostasis, Hemophilia of Georgia, Inc.
Director, Comprehensive Hemostasis Program, Emory University and Children’s Healthcare of Atlanta, Atlanta, Georgia, USA
CAROLYN M. BENNETT, MD
Assistant Professor, Department of Pediatrics, Emory University School of Medicine
Attending Physician, Aflac Cancer Center and Blood Disoders Service, Children’s Healthcare of Atlanta, Atlanta, Georgia, USA
MICHAEL A. BRIONES, DO
Assistant Professor, Department of Pediatrics, Emory University School of Medicine
Attending Physician, Aflac Cancer Center and Blood Disoders Service, Children’s Healthcare of Atlanta, Atlanta, Georgia, USA
MARY D. DARROW, MD
Resident Physician, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
AMY L. DUNN, MD
Assistant Professor, Department of Pediatrics, Emory University School of Medicine
Attending Physician, Aflac Cancer Center and Blood Disoders Service, Children’s Healthcare of Atlanta, Atlanta, Georgia, USA
JIMMIE L. EVANS, MT (ASCP)
Manager, Transfusion Medicine Laboratory Services, Emory University Hospital, Atlanta, Georgia, USA
LAWRENCE B. FIALKOW, DO
Fellow, Center for Transfusion Medicine and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
COURTNEY E. GREENE, MD
Resident Physician, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
ALFRED J. GRINDON, MD
Professor Emeritus, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
ELEANOR S. HAMILTON, MT (ASCP)
Medical Technologist, Cellular Therapies Laboratory, Emory University Hospital, Atlanta, Georgia, USA
JEANNE E. HENDRICKSON, MD
Assistant Professor, Department of Pediatrics, Emory University School of Medicine
Assistant Director, Blood Banks and Transfusion Services, Children’s Healthcare of Atlanta, Atlanta, Georgia, USA
CHRISTOPHER D. HILLYER, MD
Distinguished Service Professor of Pathology
Professor, Department of Pathology and Laboratory Medicine, Emory University School of Medicine
Professor, Department of Hematology and Medical Oncology, Emory University School of Medicine
Director, Center for Transfusion and Cellular Therapies, Atlanta, Georgia, USA
KRISTA L. HILLYER, MD
Assistant Professor, Department of Pathology and Laboratory Medicine, Emory University School of Medicine
Chief Medical Officer, Southest Division, American Red Cross Blood Services, Douglasville, Georgia, USA
SHAWN M. JOBE, MD, PhD
Assistant Professor, Department of Pediatrics, Emory University School of Medicine
Attending Physician, Aflac Cancer Center and Blood Disoders Service, Children’s Healthcare of Atlanta, Atlanta, Georgia, USA
CASSSANDRA D. JOSEPHSON, MD
Associate Professor, Department of Pathology and Laboratory Medicine, Emory University School of Medicine
Associate Director, Blood Banks and Transfusion Services, Children’s Healthcare of Atlanta, Atlanta, Georgia, USA
CHRISTINE L. KEMPTON, MD
Assistant Professor, Department of Pediatrics, Department of Hematology and Medical Oncology, Emory University School of Medicine
Assistant Professor,
Attending Physician, Aflac Cancer Center and Blood Disoders Service, Children’s Healthcare of Atlanta, Atlanta, Georgia, USA
SHANNON L. MEEKS, MD
Instructor, Department of Pediatrics, Emory University School of Medicine
Attending Physician, Aflac Cancer Center and Blood Disoders Service, Children’s Healthcare of Atlanta, Atlanta, Georgia, USA
CONNIE H. MILLER, PhD
Director, Clinical Hemostasis Laboratory,
Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention Atlanta, Georgia, USA
Preface
The editors present this inaugural edition of Transfusion Medicine and Hemostasis – Clinical and Laboratory Elements with great excitement and anticipation.
As the title indicates, we view, and have done so for some time, that both transfusion medicine and hemostasis, particularly laboratory methods and diagnostic tests employed in routine and specialized coagulation laboratories, are linked. More specifically, coagulation tests, and indeed other laboratory tests and results, are often used to guide and monitor transfusion, blood component and coagulation factor therapy. Also, transfusion strategies are used to treat patients with disorders of hemostasis which have been previously diagnosed using specialized and vital hemostasis and coagulation laboratory tests and methods. In addition, pathology, pediatric and internal medicine residents, and transfusion medicine and hematology fellows, often receive training (to varying extents) in blood banking and transfusion medicine, and in disorders and diseases of congenital and acquired coagulation defects, though a combined and appropriately focused book does not appear to exist. Moreover, books that focus on critical and technical elements of laboratory testing methodologies, in the context of transfusion and hemostasis, are few – if any. Indeed, in our institution both transfusion medicine and the coagulation/hemostasis laboratories are housed in the same clinical and administrative place – the Emory Center for Transfusion and Cellular Therapies – and joint consultation services exist. It is thus that we envisioned a manual-style book combining transfusion medicine and hemostasis/coagulation medicine. Indeed, the book before you is divided into these two main parts, as the title obviously suggests.
Not surprisingly, others have noted the interdigitation of these two fields – such as those who conceived the Transfusion Medicine/Hemostasis Clinical Trials Network, now funded by the National Institutes of Health. Also, board certification in blood banking and transfusion medicine is currently accomplished via the American Board of Pathology, and the examination has a significant emphasis on clinical hemostasis and laboratory aspects of coagulation as well as blood banking and transfusion medicine. Interestingly, board eligibility in transfusion medicine, following an accredited transfusion medicine fellowship, can be achieved directly via internal medicine, pediatrics and anesthesia residencies, in addition to pathology and adult and pediatric hematology. Thus, it is our intention that this offering be of value to trainees in many specialties, as well as fellows in transfusion medicine and hematology. Moreover, as transfusion is the most common therapeutic modality in use in the US, it is anticipated that this book will provide valuable information for practitioners in a variety of fields, including anesthesiology, surgery and obstetrics.
The format of this book is intentional, with shorter, concise chapters being the norm. In each chapter, the intent is to have clear paragraphs, bullet points, and tables and figures, with a hierarchy of headings so that presentation of key points will be most efficient. Where possible and appropriate, a common hierarchical format has been employed. Instead of an exhaustive list of references, the editors have chosen to offer a small number of key articles from which the reader may gain additional information. Even without the usual citation-based technical writing style typically employed in books, we have tried to incorporate evidence-based and data-driven prose, and have referred to specific authors, studies, and publications in a way that will allow the reader to find a specific reference even when it is not cited at the end of a chapter. We fervently hope this style will be efficient, informative and enjoyable.
As stated above, the book is divided into two main parts – transfusion medicine and hemostasis. That on transfusion medicine is further subdivided into blood banking (that is, blood collection, processing, testing and storage) and transfusion medicine (that is, components for transfusion, pretransfusion immunohematology testing, product modifications, approaches to transfusion therapy in specific clinical settings, and transfusion reactions and complications). Also included are apheresis, cellular therapy, and an introduction to tissue banking in the hospital setting. These chapters and sub-parts follow introductory chapters with common elements defining the field of blood banking and transfusion medicine, a brief history, and quality and regulatory principles. We have also included chapters focused on the role of the physician in both the blood collection facility and the transfusion service, as well as descriptions of careers in the field.
In the second main part of the book, dedicated to hemostasis, the chapters are further divided into sub-parts – clinical coagulation, laboratory-based coagulation testing, and coagulation factor products. While these three sub-parts could have been compressed into a disease-based chapter system, we felt that focus on the clinical issues, the laboratory and testing methods and details to diagnose and guide and monitor therapy, and finally the products available to treat the conditions, would be helpful and ease assimilation of the material. We hope you will agree.
Finally, in many places throughout the book, we have sections or paragraphs dedicated to international considerations. These are not exhaustive and were not meant to be, especially as regulatory requirements and practice variations vary widely throughout the developed and the developing, world. Nonetheless, the editors felt it was important to broaden the horizon of this book to have somewhat of a world view.
Again, we hope you will agree.
In closing, we are deeply dedicated to the fields of transfusion medicine and hemostasis, the ambition of striving towards optimal diagnosis, laboratory testing and therapies for patients worldwide, and the education of trainees, practitioners and future leaders in these inter-related disciplines. We hope this book will fill a void, achieve a new vision, and perhaps be seen as unique and inspired in its presentation. We ask sincerely for feedback, general or specific criticism, and suggestions as to how to improve this book, and thank you for the confidence and trust you have placed in the authors and editors.
Acknowledgments
We, the editors, would like to acknowledge the outstanding technical and professional support of Sue Rollins, and the expertise and guidance of Megan Wickline and Mara Conner and other team members at at Elsevier. Each of these individuals played an instrumental role in the creation of this textbook, and we sincerely thank them. We would like to thank our friends and families for their unconditional love and support, without which this project could not have come to fruition. We thank especially Krista, Whitney, Peter, Margot, Jackson and James Hillyer; David, Samara, Jacob and Andrew Shaz; Kim Jallow and Alexandra Zimring; and Diane, Jonathan, Jennifer, Erin and Matthew Abshire.
Part I. Blood Banking and Transfusion Medicine
Chapter 1. Blood Banking and Transfusion Medicine – the Field, the Discipline and the Industry
A safe, reliable, and available blood supply is critical to the function of complex healthcare systems worldwide. Over the past more than 100 years, blood transfusion has grown from the transfusion of small amounts of fresh whole blood, to one of the most common therapeutic medical practices (a brief history of blood transfusion can be found in Chapter 2). Indeed, since approximately 1980, blood banking and transfusion medicine has been a subspecialty in its own right, credentialed by the American Board of Pathology.
Blood Banking and Transfusion Medicine as a Discipline:
Over the past more than 25 years, blood banking and transfusion medicine has expanded to include a number of related laboratory disciplines, services and therapeutics, depending in part on the degree of complexity of the medical institution. These may include therapeutic apheresis, coagulation or specialized laboratories (hence the inclusion of clinical and laboratory coagulation in this text), hospital tissue banking, and cellular therapy – which itself may include the collection, processing, storage and distribution of human hematopoietic progenitor cells (HPC), pancreatic islet cells, and related minimally and highly manipulated cells. Some facilities classically designated as blood banks also offer HLA typing, ABO and other histocompatibility antigen/antibody and crossmatching for bone marrow, peripheral blood, and umbilical cord HPC and solid organ transplantation. While credentialed as a single entity, specifically blood banking and transfusion medicine, the terms have increasingly come to have different meanings.
Blood Banking Defined:
Blood banking now typically refers to the collection, processing, storage and distribution of whole blood and apheresis-derived blood and blood components at a blood collection facility or blood