Platelets

Platelets

3rd Edition - December 10, 2012
  • Editor: Alan Michelson
  • eBook ISBN: 9780123878380

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Description

Platelets - winner of a 2013 Highly Commended BMA Medical Book Award for Internal Medicine - is the definitive current source of state-of-the-art knowledge about platelets and covers the entire field of platelet biology, pathophysiology, and clinical medicine. Recently there has been a rapid expansion of knowledge in both basic biology and the clinical approach to platelet-related diseases including thrombosis and hemorrhage. Novel platelet function tests, drugs, blood bank storage methods, and gene therapies have been incorporated into patient care or are in development. This book draws all this information into a single, comprehensive and authoritative resource.

Key Features

  • Highly Commended BMA Medical Book Award 2013: Internal Medicine
  • Comprehensive and definitive source of knowledge about platelets for clinicians, pathologists and scientists
  • Integrates the entire field of platelet biology, pathophysiology, and clinical medicine
  • Full color reference comprising 64 chapters, 1400 pages, and 16,000 references
  • Contributions from 126 world leaders in their fields
  • New chapters on topics such as the regulation of platelet life span, platelet microRNAs, GPVI and CLEC-2, monitoring of antiplatelet therapy, novel antiplatelet therapy, and making platelets ex vivo

Readership

Hematologists, cardiologists, blood bankers, stroke physicians, pathologists, researchers in thrombosis and hemostasis, and students and fellows working in these fields

Table of Contents

  • Foreword: A Brief History of Ideas About Platelets in Health and Disease

    I The Role of Platelets in Human Hemostasis, Platelet Transfusion, and the Bleeding Time

    II Immune Thrombocytopenia

    III Alloantigens, Single Nucleotide Polymorphisms, and Alloimmune Thrombocytopenias

    IV Platelet Physiology, Assays of Platelet “Adhesiveness”, ADP, Platelet Aggregation, Myocardial Infarction, and P2Y12 Antagonists

    V Aspirin, Arachidonic Acid, Prostaglandins, Gpiib-iiia, Nitric Oxide, Endothelial Gpiib-iiia, and Angiogenesis

    VI Clot Retraction, Glanzmann Thrombasthenia, GPIIb-IIIa Receptor, and GPIIb-IIIa Antagonists

    VII Bernard-Soulier Syndrome, the Gpib-IX-V Complex, von Willebrand Factor, Shear, ADAMTS-13, and Thrombotic Thrombocytopenic Purpura

    VIII Thrombin-induced Platelet Activation

    IX Platelets and Metastases

    X Reflections on the Past and Thoughts About the Future

    Part I: Platelet Biology

    Chapter 1. The Evolution of Mammalian Platelets

    I Introduction

    II Invertebrates

    III Nonmammalian Vertebrates

    IV Comparative Hemostasis

    V A Comparison of Human Platelets and Limulus Amebocytes

    VI The Evolution of Hemostasis and Blood Coagulation

    VII Megakaryocytes and Mammals

    VIII Conclusions

    Acknowledgments

    References

    Chapter 2. Megakaryocyte Development and Platelet Formation

    I Introduction

    II Megakaryocyte Development

    III Platelet Formation

    IV Regulation of Megakaryocyte Development and Platelet Formation

    V Murine Model Systems and Human Diseases as Tools to Study Platelet Biogenesis

    References

    Chapter 3. The Regulation of Platelet Life Span

    I Introduction

    II History

    III Methods for the Measurement of Platelet Life Span

    IV An Introduction to Apoptosis

    V An Apoptotic Pathway Regulates Platelet Survival and Life Span

    VI Distinct Pathways Promote Platelet Procoagulant Function

    VII Clearance Mechanisms of Platelets and Clearance Signals

    VIII Future Questions

    Acknowledgments

    References

    Chapter 4. Platelet Genomics

    I Introduction

    II Human Genomics

    III Platelet Genomic Association Studies: Phenotype Issues

    IV Genome-Wide Association Studies (GWAS)

    V Cardiovascular Disease Genomic (DNA) Association Studies

    VI Platelet Genomic Studies with Intermediate (Platelet QTL) Outcomes

    VII Platelet-Megakaryocyte Transcriptome Association Studies

    VIII Mechanistic Insights from Platelet Genomic Studies

    IX Platelet Pharmacogenetics

    X GWAS Perspectives

    XI The Future

    References

    Chapter 5. Platelet microRNAs

    I The microRNA Pathway of Human Cells

    II Platelets

    III The microRNA Pathway of Platelets

    IV Use of Platelet microRNAs as Biomarkers

    V Therapeutic Applications

    VI Conclusion and Perspectives

    Acknowledgments

    References

    Chapter 6. The Platelet Proteome

    I Introduction

    II The Platelet Proteome

    III Factors that Influence the Make-Up of the Platelet Proteome

    IV Evaluating the Platelet Proteome

    V Summary and Future Directions

    References

    Chapter 7. Platelet Structure

    I Introduction

    II Peripheral Zone

    III The Sol-Gel Zone

    IV Organelle Zone

    V Platelet Membrane Systems

    References

    Chapter 8. The Platelet Cytoskeleton

    I Introduction

    II The Structure of the Resting Platelet

    III The Cytoskeleton of the Resting Platelet

    IV The Structure of the Activated Platelet

    V Signals Activating Actin Assembly

    VI Membrane Dynamics and Actin Filament Turnover in Platelets

    VII Platelet Contraction

    VIII Diseases of the Platelet Cytoskeleton

    References

    Chapter 9. Platelet Receptors

    I Introduction

    II Integrins

    III Leucine-Rich Repeat (LRR) Family

    IV Seven-Transmembrane Receptors

    V Immunoglobulin Superfamily

    VI C-Type Lectin Receptor Family

    VII Tetraspanins

    VIII Glycosyl Phosphatidylinositol (GPI)-Anchored Proteins

    IX Glycosaminoglycan-Carrying Receptors

    X Tyrosine Kinase Receptors

    XI Miscellaneous Platelet Membrane Glycoproteins

    Acknowledgment

    References

    Chapter 10. The GPIb-IX-V Complex

    I Introduction/Structure

    II Function

    III Signaling

    IV Conclusions

    References

    Chapter 11. GPVI and CLEC-2

    I Introduction to Platelet ITAM and HemITAM Receptors

    II GPVI

    III CLEC-2

    IV Conclusions

    References

    Chapter 12. Integrin αIIbβ3

    I Introduction

    II αIIbβ3 as an Integrin and a Platelet Protein

    III Structure of αIIbβ3

    IV “Inside-Out” Signaling and αIIbβ3 Activation

    V Conclusions

    References

    Chapter 13. Protease-Activated Receptors

    I Introduction

    II Structure and Mechanism of Activation of PARS

    III A Dual Protease-Activated Receptor System for Human Platelet Activation

    IV Pharmacology of PAR Ligands and Antagonists in Platelets

    V PAR1 and PAR4 Signaling in Platelets

    VI Role of Secreted ADP in Thrombin-Induced Platelet Aggregation

    VII PAR-Activated Prothrombinase Activity and Thrombin Generation

    References

    Chapter 14. The Platelet P2 Receptors

    I P2 Receptors

    II Roles of Adenine Nucleotides in Platelet Function

    III P2Y1

    IV P2Y12

    V P2X1

    VI Interplay Between the Platelet P2 Receptors

    VII Desensitization of the Platelet P2 Receptors

    VIII Conclusions

    References

    Chapter 15. PECAM-1

    I Introduction

    II PECAM-1 Genomic Organization and Protein Domain Structure

    III Expression and Adhesive Properties of the Extracellular Domain

    IV Phosphorylation, Cytoskeletal Association, and Protein Interactions of the PECAM-1 Cytoplasmic Domain

    V PECAM-1 as a Bidirectional Regulator of Platelet Reactivity and Thrombosis

    VI Allelic and Soluble Isoforms of PECAM-1 and their Association with Cardiovascular Disease

    VII Conclusions

    References

    Chapter 16. Interactions Between Platelets, Leukocytes and the Endothelium

    I Mediators

    II Functional Consequences

    III Pathophysiologic Roles

    IV Concluding Remarks

    Acknowledgments

    References

    Chapter 17. Inhibition of Platelet Function by the Endothelium

    I Introduction

    II Nitric Oxide

    III Prostacyclin

    IV CD39 (NTPDase-1)

    V Summary

    Acknowledgements

    References

    Chapter 18. Platelet Secretion

    I Introduction: Platelet Granules

    II Formation of Platelet Granules

    III Platelet Granule Content

    IV Mechanisms of Platelet Granule Secretion

    V Function of Platelet Granule Secretion

    VI Platelet Granule Disorders

    VII Conclusions

    Acknowledgments

    References

    Chapter 19. Signal Transduction During Platelet Plug Formation

    I Overview

    II Early Events of Platelet Activation via G-Protein-Coupled Receptors

    III An Agonist-Centric View of Platelet Activation

    IV Contact-Dependent and Contact-Facilitated Events that Reinforce Platelet Activation

    V Regulators of Platelet Activation: Obtaining an Optimal Response to Injury

    VI Concluding Thoughts

    References

    Chapter 20. Platelet Thrombus Formation in Flowing Blood

    I Introduction

    II Initial Events in Thrombus Formation under Flow

    III Thrombus Propagation under Flow

    IV Conclusions

    References

    Chapter 21. Interactions Between Platelets and the Coagulation System

    I Overview of the Role of Platelets in Hemostasis

    II Enzyme Complex Formation Regulates the Coagulant Response

    III Model Systems Defining the Role of Platelets in Tissue FACTOR-INITIATED Thrombin Generation

    IV Intrinsic Platelet Molecules Involved in the Coagulant Response

    V Coagulation Reactions Supported by the Activated Platelet Surface

    VI Positive and Negative Effectors of Platelet Coagulant Activity

    VII Summary

    Acknowledgement

    References

    Chapter 22. Platelet-Derived Microparticles

    I Introduction

    II Microparticle Structure

    III Detection of Microparticles

    IV Formation and Clearance of Platelet Microparticles

    V Microparticle Function

    VI Clinical Disorders Associated with Microparticles

    VII Future Developments

    References

    Chapter 23. The Role of Platelets in Fibrinolysis

    I Introduction

    II Key Mechanisms and Components of Fibrinolysis

    III Inhibitors of Fibrinolysis

    IV Platelet-Associated Fibrinolytic Activity

    V Integrin αIIbβ3 Interactions

    VI Platelet-Mediated Effects on Fibrin Structure

    VII Plasmin-Mediated Platelet Activation

    VIII Platelet Disorders and Fibrinolysis

    IX Net Effects

    Acknowledgments

    References

    Chapter 24. The Role of Platelets in Angiogenesis

    I The Role of Platelets in Angiogenesis

    II Platelets and Angiogenesis in Tissue Regeneration and Wound Healing

    III The Effects of Platelets on Tumor Dynamics

    References

    Chapter 25. Platelet Function in the Newborn

    I Introduction

    II Platelet Number and Size

    III Platelet Production

    IV Platelet Structure

    V Measurements of Platelet Function

    VI Platelet Activation During Delivery

    VII Platelet Adhesion

    VIII Platelet Signal Transduction

    IX Platelet Secretion

    X Platelet Procoagulant Activity

    XI Effects of Drugs on Fetal and Neonatal Platelet Function

    XII Effects of Maternal Disease on Fetal and Neonatal Platelet Function

    XIII Conclusions

    References

    Part II: Tests of Platelet Function

    Chapter 26. Clinical Tests of Platelet Function

    I Introduction

    II Early Tests of Platelet Number and Function

    III Overview of Currently Available Platelet Function Tests

    IV Use of Platelet Function Testing in the Clinical Setting

    V Summary and the Future of Platelet Function Testing

    References

    Chapter 27. Platelet Counting

    I Introduction

    II Manual Platelet Counting

    III Automated Platelet Counting

    IV Reticulated Platelets/Immature Platelet Fraction

    V Conclusions

    References

    Chapter 28. Platelet Aggregation

    I Overview of Methods for the Evaluation of Platelet Aggregation

    II Preparation of Samples for Platelet Aggregation Tests

    III Analytical Considerations and Potential Interferences for Aggregation Tests

    IV Quantitative Endpoints of Aggregation and Release Assays

    V Aggregation Interpretation in the Assessment of Bleeding Disorders

    VI Quality Evaluation of Platelet Aggregation Tests

    References

    Chapter 29. Flow Cytometry

    I Introduction

    II Measurement of Platelet Activation

    III Diagnosis of Specific Disorders

    IV Monitoring of Antiplatelet Agents

    V Monitoring of Thrombopoiesis

    VI Blood Bank Applications

    VII Platelet-Associated IgG

    VIII Platelet Count

    IX Other Research Applications

    References

    Chapter 30. Monitoring of Antiplatelet Therapy

    I Introduction

    II Rationale for Monitoring Antiplatelet Therapy

    III Aspirin

    IV Clopidogrel

    V Role of Platelet Function Measurement in Patients Undergoing Coronary Artery Bypass Surgery

    VI Monitoring Antiplatelet Therapy During Combination Therapies

    VII Monitoring of Antiplatelet Therapy in the Medically Managed Acute Coronary Syndrome Patient

    VIII Monitoring Antiplatelet Therapy During Clopidogrel and Proton Pump Inhibitor Therapy

    IX Monitoring Antiplatelet Therapy During GPIIb-IIIa Antagonist Therapy

    X Guidelines

    XI Future

    References

    Chapter 31. Real Time In Vivo Imaging of Platelets During Thrombus Formation

    I Introduction

    II Equipment and Methods

    III Data Acquisition and Analysis

    IV Study of Thrombus Formation

    V Conclusions

    References

    Part III: The Role of Platelets in Disease

    Chapter 32. Atherothrombosis and Coronary Artery Disease

    I Platelets Initiate Atherosclerosis—A Model of Platelet-Induced Disease

    II Platelet Adhesion Promotes Initiation of Atherosclerosis

    III Platelet Secretion and Generation of Cytokines

    IV Platelets and Dendritic Cells

    V Impact of Platelets on Endothelial Regeneration

    VI Platelets and Thrombosis in the Course of Atherosclerosis

    VII Therapeutic Implications and Management of Coronary Artery Disease

    VIII Conclusions

    References

    Chapter 33. Central Nervous System Ischemia

    I Introduction

    II Ischemic Cerebrovascular Disease

    III Platelet Activation in the Development of Focal Cerebral Ischemia

    IV Hemorrhagic Transformation

    V Antiplatelet Interventions in Cerebral Ischemia

    VI Carotid Artery Atherothrombotic Disease

    VII Cerebral Embolism from a Cardiac Source

    VIII Conclusions

    References

    Chapter 34. Peripheral Vascular Disease

    I Overview of Peripheral Arterial Disease

    II Platelet-Vessel Wall Interactions in PAD

    III Characteristics of Platelet Function in PAD

    IV Platelet-Focused Therapy in PAD

    V Platelets in Venous Disease

    VI Conclusions

    References

    Chapter 35. Diabetes Mellitus

    I Accelerated Atherothrombosis: Epidemiological and Clinical Findings

    II Are Platelets the Key Player in Diabetic Atherothrombosis?

    III Mechanisms Contributing to In Vivo Platelet Activation

    IV Antiplatelet Therapy for the Primary and Secondary Prevention of Atherothrombotic Events

    V Less-than-Expected Response to Aspirin

    VI Possible Determinants of Hyporesponsiveness to Aspirin in Diabetes

    VII Conclusions

    Acknowledgments

    References

    Chapter 36. Inflammation

    I Introduction

    II Platelet Interactions with Endothelium and Leukocytes

    III Platelet Signaling Receptors, Integrins, and Immunoreceptors

    IV Platelet Toll-Like Receptors

    V The Platelet Secretome and Other Modes of Intercellular Signaling in Inflammation and Immune Syndromes

    VI The Platelet Transcriptome and New Mechanisms for Signal-Dependent Modification of the Platelet Proteome in Inflammation

    VII Platelets in Innate and Adaptive Immune Responses

    VIII Platelets in Inflammation: Animal Models of Disease

    IX Platelets in Human Inflammatory Diseases and Syndromes

    X Platelets: Protean Activities in Defense and Disease

    Acknowledgments

    References

    Chapter 37. Antimicrobial Host Defense

    I Introduction

    II Mammalian Platelets are Multipurpose Host Defense Cells

    III Early Studies were Interpreted to Suggest Platelets Promote Infection

    IV Platelets Likely Play Multiple Roles in Antimicrobial Host Defense

    V Platelets Contain Antimicrobial Effector Molecules that Contribute to Host Defense

    VI Platelet Host Defense Polypeptides Likely Function via Multiple Mechanisms of Action

    VII Platelet Host Defense Polypeptides Potentiate Conventional Antibiotics

    VIII PMPs and Platelet Kinocidins Modulate Pathogen Interactions with Platelets and Endothelial Cells

    IX Platelets Modulate Complement Activation

    X Platelets Influence the Host Defense Roles of Lymphocytes

    XI Platelets Potentiate the Antimicrobial Functions of Leukocytes

    XII Platelets are Integral to Antimicrobial Host Defense In Vivo

    XIII Certain Pathogens May Subvert Platelet Host Defenses

    XIV Correlates of Platelet Quantity or Function and Risk of Infection

    XV Future Studies

    XVI Summary

    Acknowledgment

    References

    Chapter 38. Tumor Growth and Metastasis

    I Introduction

    II The Platelet–Tumor Cell Axis

    III Platelet–Tumor Cell Emboli and Ischemia

    IV Platelets, Tumor Cells, and Innate Immunity

    V Platelets and Angiogenesis

    VI Platelet Activation and Metastasis

    VII Platelet Therapies and Cancer

    VIII Conclusion and Perspectives

    References

    Part IV: Disorders of Platelet Number and Function

    Chapter 39. The Clinical Approach to Disorders of Platelet Number and Function

    I Introduction

    II Clinical History

    III Physical Examination

    IV Clinical Tests

    V Differential Diagnosis

    VI Specific Disorders

    Reference

    Chapter 40. Immune Thrombocytopenia (ITP)

    I Introduction

    II Incidence

    III Etiology and Pathophysiology

    IV Diagnosis and Clinical Assessment

    V Management

    VI Prognosis

    VII Summary

    Acknowledgments

    References

    Chapter 41. Drug-Induced Thrombocytopenia

    I Introduction

    II Drug-Induced Suppression of Platelet Production

    III Drug-Induced Platelet Destruction by Nonimmune Mechanisms

    IV Drug-Induced Platelet Destruction by Immune Mechanisms

    References

    Chapter 42. Heparin-Induced Thrombocytopenia

    I Introduction

    II Historical Aspects and Nomenclature

    III Pathogenesis

    IV Frequency

    V Clinical Features

    VI Diagnosis

    VII Management

    References

    Chapter 43. Thrombotic Thrombocytopenic Purpura and the Hemolytic-Uremic Syndrome

    I Introduction

    II TTP

    III Shiga Toxin-associated HUS

    IV Atypical HUS

    Acknowledgments

    References

    Chapter 44. Thrombocytopenia in Pregnancy

    I Introduction

    II Specific Causes of Pregnancy-Associated Thrombocytopenia

    III Summary and Conclusions

    References

    Chapter 45. Thrombocytopenia in the Newborn

    I Introduction

    II Fetal Megakaryocytopoiesis and Platelet Production

    III Incidence of Neonatal Thrombocytopenia

    IV Natural History of Neonatal Thrombocytopenias

    V Conditions Leading to Clinically Significant Neonatal Thrombocytopenia

    VI Diagnosis of Neonatal Thrombocytopenia

    VII Platelet Transfusion for Neonatal Thrombocytopenia

    VIII Future Therapeutic Options for Neonatal Thrombocytopenia

    IX Summary

    References

    Chapter 46. Alloimmune Thrombocytopenia

    I Introduction

    II Fetal and Neonatal Alloimmune Thrombocytopenia

    III Post-Transfusion Purpura

    IV Passive Alloimmune Thrombocytopenia

    V Unresolved Questions and Future Directions

    References

    Chapter 47. Inherited Thrombocytopenias

    I Introduction

    II The Microthrombocytic Thrombocytopenias

    III The Normothrombocytic Thrombocytopenias

    IV The Macrothrombocytic Thrombocytopenias

    V An Approach to Patients with Suspected Congenital Thrombocytopenia

    References

    Chapter 48. Pseudothrombocytopenia

    I Introduction

    II EDTA-Dependent Pseudothrombocytopenia

    III Citrate-Dependent Pseudothrombocytopenia

    IV Other Anticoagulants

    V Clinical Aspects

    VI Pseudothrombocytopenia Agglutinins as Natural Antibodies

    VII Clinical Laboratory Procedures

    VIII Pseudothrombocytopenia Due to Platelet Satellitism

    IX Pseudothrombocytopenia Due to Therapeutic Monoclonal Antibodies

    X Conclusions

    References

    Chapter 49. Thrombocytosis and Essential Thrombocythemia

    I Introduction

    II Congenital Thrombocytosis

    III Reactive Thrombocytosis

    IV Primary Thrombocytosis and the Myeloproliferative Neoplasms

    V Distinguishing Reactive Thrombocytosis from Primary Thrombocytosis

    VI Essential Thrombocythemia

    VII Concluding Comments

    References

    Chapter 50. Congenital Disorders of Platelet Function

    I Introduction

    II Classification of Congenital Disorders of Platelet Function

    III Abnormalities of the Platelet Receptors for Adhesive Proteins

    IV Abnormalities of the Platelet Receptors for Soluble Agonists

    V Defects of Platelet Granules

    VI Defects of Signal Transduction

    VII Abnormalities of Membrane Phospholipids

    VIII Miscellaneous Disorders of Platelet Function

    IX Hereditary Defects of Adhesive Proteins, Affecting Platelet Function

    X Prevalence of and Diagnostic Evaluation of Congenital Disorders of Platelet Function

    XI Treatment of Congenital Platelet Function Disorders

    XII Future Avenues of Research

    XIII Conclusions

    References

    Chapter 51. Acquired Disorders of Platelet Function

    I Introduction

    II Uremia

    III Myeloproliferative Diseases

    IV Acute Leukemias and Myelodysplastic Syndromes

    V Dysproteinemias

    VI Acquired von Willebrand Disease

    VII Acquired Storage Pool Disease

    VIII Antiplatelet Antibodies and Platelet Dysfunction

    IX Liver Disease

    X Miscellaneous Conditions with Impaired Platelet Function

    XI Drugs That Inhibit Platelet Function

    Acknowledgments

    References

    Chapter 52. Cardiopulmonary Bypass

    I Introduction

    II Clinical Aspects of CPB Relevant to Platelet Pathophysiology

    III Inflammation and CPB

    IV Clinical Hemostatic Alterations During and After CPB

    V Quantitative Platelet Abnormalities During CPB

    VI Qualitative Platelet Abnormalities During CPB

    VII Diagnostic and Therapeutic Issues in CPB Hemostasis

    References

    Part V: Antiplatelet Therapy

    Chapter 53. Aspirin

    I Historical Background

    II Mechanism of Action

    III Pharmacokinetics and Pharmacodynamics

    IV Drug Interactions

    V Inter-Individual Variability in Drug Response

    VI Clinical Readouts of Platelet COX-1 Inactivation

    VII Balance of Benefits and Risks

    VIII Conclusions

    Acknowledgments

    References

    Chapter 54. ADP Receptor Antagonists

    I Introduction

    II Thienopyridines

    III Direct P2Y12 Antagonists

    IV Conclusions

    References

    Chapter 55. αIIbβ3 (GPIIb-IIIa) Antagonists

    I Introduction

    II General Information and Mechanism of Action

    III Landmark Clinical Trials: Percutaneous Coronary Intervention

    IV Landmark Clinical Trials: Non-ST-Elevation Acute Coronary Syndromes

    V Landmark Clinical Trials: ST-Elevation Myocardial Infarction

    VI Relative Efficacy of GPIIb-IIIa Antagonists

    VII Special Circumstances and Alternative Strategies to GPIIb-IIIa Antagonists

    VIII Side Effects

    IX Conclusions

    References

    Chapter 56. Dipyridamole

    I Introduction

    II Absorption and Metabolism

    III Mechanisms of Action

    IV Side Effects

    V Conclusions

    References

    Chapter 57. Cilostazol

    I Introduction

    II Mechanism of Action

    III Antiplatelet Effects

    IV Antithrombotic Effects

    V Other Effects

    VI Clinical Results

    References

    Chapter 58. Novel Antiplatelet Therapies

    I Introduction

    II Platelet Biology

    III Current Antiplatelet Therapies

    IV Novel Antiplatelet Therapies

    V Conclusions

    References

    Part VI: Therapy to Increase Platelet Numbers and/or Function

    Chapter 59. Thrombopoietin Mimetics

    I Introduction

    II TPO Structure

    III The TPO Gene and Its Regulation

    IV Functions of TPO

    V Physiology of TPO

    VI Pathophysiology of TPO

    VII Therapeutic Thrombopoietins

    VIII Clinical Effects of Therapeutic Thrombopoietins: Animal Studies

    IX Clinical Effects of Therapeutic Thrombopoietins: Human Studies

    X Adverse Effects of Therapeutic Thrombopoietins in Humans

    XI Interleukin-11 (A Non-TPO Thrombopoietic Growth Factor)

    References

    Chapter 60. Desmopressin (DDAVP)

    I Introduction

    II Management with Desmopressin of Mild Hemophilia A and von Willebrand Disease

    III Desmopressin as a General Hemostatic Agent

    IV Side Effects

    V Mechanisms of Action of Desmopressin

    VI Conclusions

    References

    Chapter 61. Factor VIIa

    I Introduction

    II Pharmacology

    III rFVIIa in the Treatment of Thrombocytopenia

    IV rFVIIa in the Treatment of Platelet Function Disorders

    V Adverse Events

    VI Mechanisms of Action

    VII FVIIa Analogs in Clinical Development

    VIII Conclusions

    Acknowledgements

    References

    Chapter 62. Platelet Transfusion Medicine

    I Introduction

    II Platelet Preparation

    III Platelet Storage and Storage Injury

    IV Postcollection Processing

    V Platelet Transfusion Therapy

    VI Adverse Reactions to Platelet Transfusion

    VII Thrombopoietic Growth Factors in Platelet Transfusion Therapy

    VIII Conclusions

    References

    Chapter 63. Making Platelets Ex Vivo

    I Introduction

    II Generating Human Megakaryocytes and Platelets Ex Vivo

    III Targeted Therapy via Platelets

    IV Conclusions

    References

    Chapter 64. Gene Therapy for Platelet Disorders

    I Introduction

    II Approach to Gene Transfer for Platelet Disorders

    III Advances in Retrovirus-Mediated Transduction for Platelets

    IV State-of-the-Art Animal Models for Disorders Affecting Platelets

    V Conclusions

    Acknowledgments

    References

    Index

Product details

  • No. of pages: 1400
  • Language: English
  • Copyright: © Academic Press 2012
  • Published: December 10, 2012
  • Imprint: Academic Press
  • eBook ISBN: 9780123878380

About the Editor

Alan Michelson

Alan Michelson
Dr. Michelson is Professor of Pediatrics and Professor of Medicine at Harvard Medical School in Boston, Massachusetts, U.S.A. He is also the Director of the Center for Platelet Research Studies (www.platelets.org) and the Director of the Thrombosis and Anticoagulation Program at Dana-Farber/Boston Children's Cancer and Blood Disorders Center. After receiving his medical degree with honors from the University of Adelaide, Australia, Dr. Michelson continued his medical and research training on a Fulbright Scholarship at Boston Children’s Hospital, Brigham and Women’s Hospital, and Harvard Medical School. In 2019 he received the International Society on Thrombosis and Haemostasis (ISTH) Esteemed Career Award. Dr. Michelson has been an invited participant in numerous National Institutes of Health working groups, international workshops and consensus conferences. He is the co-organizer and co-chair of the biennial International Platelets Symposium. Dr. Michelson is a past Chairman of the Platelet Physiology Scientific Subcommittee of the ISTH. He has published more than 450 original research articles, original research abstracts, and invited reviews – nearly all on the topic of platelets. Dr. Michelson has been the principal investigator on more than 100 research grants. He has been an invited speaker at over 200 major medical conferences worldwide. Dr. Michelson is an inventor on two awarded and three provisional U.S. patents.

Affiliations and Expertise

Professor of Pediatrics and Professor of Medicine, Harvard Medical School, Boston, MA, USA; Director, Center for Platelet Research Studies and Director, Thrombosis and Anticoagulation Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA