Hemostasis and Thrombosis - part 1 pot

V m Hemostasis & Thrombosis 2nd Edition Thomas G. DeLoughery a d e m e c u V a d e m e c u m Table of contents 1. Basics of Coagulation 2. Tests of Hemostasis and Thrombosis 3. Bleeding Disorders: A General Approach 4. Hemophilia 5. Von Willebrand Disease 6. Other Inherited Bleeding Disorders 7. Acquired Bleeding Disorders 8. Disseminated Intravascular Coagulation 9. Liver and Renal Disease The Vademecum series includes subjects generally not covered in other handbook series, especially many technology-driven topics that reflect the increasing influence of technology in clinical medicine. The name chosen for this comprehensive medical handbook series is Vademecum, a Latin word that roughly means “to carry along”. In the Middle Ages, traveling clerics carried pocket-sized books, excerpts of the carefully transcribed canons, known as Vademecum. In the 19th century a medical publisher in Germany, Samuel Karger, called a series of portable medical books Vademecum. The Landes Bioscience Vademecum books are intended to be used both in the training of physicians and the care of patients, by medical students, medical house staff and practicing physicians. We hope you will find them a valuable resource. All titles available at www.landesbioscience.com LANDES BIOSCIENCE 10. Cardiac Bypass 11. Immune Thrombocytopenia 12. Thrombotic Microangiopathy (TTP/HUS) 13. Non-Blood Product Agents for Bleeding Disorders 14. Transfusion Therapy and Massive Transfusions 15. Deep Venous Thrombosis and Pulmonary Embolism 16. Thrombosis in Unusual Sites 17. Hypercoagulable States 18. Acquired Hypercoagulable States LANDES BIOSCIENCE (excerpt) IXa X VIII Ca Ca Ca Ca CaCaCaCa IXa X VIII Ca Ca Ca Ca CaCaCaCa ISBN 1-57059- 686- 7 9781570 596865 Thomas G. DeLoughery, M.D. Oregon Health Sciences University Portland, Oregon, U.S.A. Hemostasis and Thrombosis 2nd Edition G EORGETOWN , T EXAS U.S.A. vademecum L A N D E S B I O S C I E N C E VADEMECUM Hemostasis and Thrombosis, 2nd Edition LANDES BIOSCIENCE Georgetown, Texas U.S.A. Copyright ©2004 Landes Bioscience All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Printed in the U.S.A. Please address all inquiries to the Publisher: Landes Bioscience, 810 S. Church Street, Georgetown, Texas, U.S.A. 78626 Phone: 512/ 863 7762; FAX: 512/ 863 0081 ISBN: 1-57059-686-7 Library of Congress Cataloging-in-Publication Data DeLoughery, Thomas G. Hemostasis and thrombosis / Thomas G. DeLoughery 2nd ed. p. ; cm. (Vademecum) Includes bibliographical references and index. ISBN 1-57059-686-7 1. Thrombosis Handbooks, manuals, etc. 2. Hemostasis Handbooks, manuals, etc. 3. Blood coagulation disorders Handbooks, manuals, etc. I. Title. II. Series. [DNLM: 1. Hemostasis Handbooks. 2. Blood Coagulation Disorders therapy Handbooks. 3. Coagulants therapeutic use Handbooks. 4. Hemostatic Tech- niques Handbooks. 5. Thrombosis prevention & control Handbooks. WH 39 D362h 2004] RC694.3.D44 2004 616.1'57 dc22 2003027907 While the authors, editors, sponsor and publisher believe that drug selection and dosage and the specifications and usage of equipment and devices, as set forth in this book, are in accord with current recommendations and practice at the time of publication, they make no warranty, expressed or implied, with respect to material described in this book. In view of the ongoing research, equipment development, changes in governmental regulations and the rapid accumulation of information relating to the biomedical sciences, the reader is urged to carefully review and evaluate the information provided herein. Dedication To my wife Jean and my daughter Emma Artwork by Emma DeLoughery Contents List of Tables xi Preface xv 1. Basics of Coagulation 1 Formation of Fibrin 1 The “Quaternary Complex” 3 Initiation of Coagulation 4 Thrombin 6 The Role of Factor XI 9 Fibrinolysis 9 Platelet Production and Life Span 11 Function of Platelets 11 Natural Anticoagulants 15 2. Tests of Hemostasis and Thrombosis 17 Bleeding Disorders 17 Specific Assays for Bleeding Disorders 17 Tests for DIC (Disseminated Intravascular Coagulation) 21 Thrombotic Disorders 23 Hypercoagulable States 25 3. Bleeding Disorders: A General Approach 26 Is the Bleeding Real? 26 Is the Bleeding Due to Factor Deficiencies or Platelet Defects? 27 Is It an Acquired or Inherited Disorder? 27 What Tests Do I Need to Perform and How Do I Interpret Them? 27 4. Hemophilia 29 Introduction 29 Pathophysiology and Classification 29 Symptoms 29 Diagnosis 30 Therapy 31 Therapy of Hemophilia B (Factor IX Deficiency) 33 Guideline for Specific Bleeds 33 Surgery in the Patient with Hemophilia 34 Inhibitors 35 5. Von Willebrand Disease 37 Introduction 37 Pathogenesis and Classification 37 Signs and Symptoms 38 Te sting 39 Therapy 40 Pregnancy 42 6. Other Inherited Bleeding Disorders 43 Platelet Defects 43 Named Platelet Disorders 44 Less Common Coagulation Disorders 45 7. Acquired Bleeding Disorders 49 Thrombocytopenia 49 Diagnostic Approach 49 Etiologies of Thrombocytopenia 50 Acquired Coagulation Factor Deficiency 54 Specific Acquired Factor Deficiencies 56 Acquired von Willebrand Disease 58 8. Disseminated Intravascular Coagulation 60 Pathogenesis 60 Etiology 61 Clinical Presentation 62 Diagnosis 62 Therapy 63 9. Liver and Renal Disease 65 Liver Disease 65 Pathogenesis of Defects 65 Preparation for Surgery 67 Uremia 68 Pathogenesis 68 Evaluation 69 Therapy 69 10. Cardiac Bypass 71 Introduction 71 Preoperative Coagulation Defects 71 Cardiopulmonary Bypass 72 Prevention and Therapy 73 Approach to the Bleeding Bypass Patient 73 Special Situations 74 11. Immune Thrombocytopenia 76 Introduction 76 Pathogenesis and Epidemiology 76 Symptoms 76 Diagnosis 76 Therapy 77 A Practical Approach to the Refractory Patient 79 Surgery 79 Pregnancy 80 Evans Syndrome 80 12. Thrombotic Microangiopathy (TTP/HUS) 83 Introduction 83 Classification 83 Classic Thrombotic Thrombocytopenic Purpura (TTP) 84 Pathogenesis 85 Differential Diagnosis 85 Therapy 86 Refractory Patients 86 Other Thrombotic Microangiopathies 87 Hemolytic Uremic Syndrome (HUS) 87 Pregnancy-Related TM 88 Therapy-Related HUS 89 13. Non-Blood Product Agents for Bleeding Disorders 91 Desmopressin 91 Aminocaproic Acid and Tranexamic Acid 92 Aprotinin 93 Conjugated Estrogens 93 Recombinant VIIa (rVIIa) 93 14. Transfusion Therapy and Massive Transfusions 95 Platelets 95 Fresh Frozen Plasma (FFP) 97 Cryoprecipitate 98 Corrections of Defects before Procedures in Patients with Liver Disease and Other Coagulopathies 98 Massive Transfusions 99 15. Deep Venous Thrombosis and Pulmonary Embolism 102 Natural History 102 Diagnostic Tests for Pulmonary Embolism and Deep Venous Thrombosis 102 Tr eatment of Deep Venous Thrombosis 108 Special Situations 110 Duration of Therapy 110 Prophylaxis 111 Who Is at Risk? 111 The Treatment Regimens 112 The Situations 113 16. Thrombosis in Unusual Sites 116 Upper Extremity Thrombosis 116 Cerebral Vein Thrombosis 116 Adrenal Infarction 117 Budd-Chiari Syndrome 117 Portal Vein Thrombosis 118 Renal Vein Thrombosis 118 Visceral Vein Thrombosis 118 Retinal Vein Thrombosis 119 Priapism 119 17. Hypercoagulable States 121 When to Suspect a Hypercoagulable State 121 Why Diagnose Hypercoagulable States? 122 Approach to the Patient Suspected of Having a Hypercoagulable State 122 The Congenital Hypercoagulable States 123 18. Acquired Hypercoagulable States 127 Inflammatory Bowel Disease 127 Surgery 128 Nephrotic Syndrome and Other Renal Disease 128 Paroxysmal Nocturnal Hemoglobinuria (PNH) 129 Beçhet’s Disease 129 Hemolytic Disorders 130 Homocysteinemia 130 Air Travel 132 19. Antiphospholipid Antibody Syndrome 133 Antiphospholipid Antibodies (APLA) 133 Semantics 133 Who Gets APLA? 134 APLA: Clinical Associations 134 Catastrophic APLA (CAPS) 136 Diagnostic Approach 136 Therapy 137 Difficulties in Monitoring Anticoagulation 138 20. Antithrombotic Therapy for Cardiac Disease 140 Ischemic Heart Disease 140 Acute Myocardial Infarction: Acute Therapy 141 Prevention of Embolism 144 21. Stroke and Peripheral Vascular Disease 149 Stroke 149 Peripheral Vascular Disease 152 Antithrombotic Therapy for Peripheral Vascular Disease 153 22. Heparin and Heparin-Like Drugs 155 Antithrombotic Use of Low Molecular Weight Heparin 155 Antithrombotic Use of Standard Heparin 157 Antithrombotic Use of Pentasaccharides 158 Special Problems 158 Complications of Heparin 159 23. Direct Thrombin Inhibitors 164 Introduction 164 Argatroban 164 Lepirudin 164 Bivalirudin 165 Ximelagatran 166 24. Warfarin 168 Therapeutic Range of INR 170 Warfarin Resistance and Unstable INRS 173 Correction of Warfarin Overdose 174 Management of the Patient on Warfarin Who Needs a Procedure 175 25. Antiplatelet Agents 177 Aspirin 177 Ticlopidine 178 Clopidogrel 179 Dipyridamole 180 Abciximab 180 Tirofiban 181 Eptifibatide 182 Further Use of GP IIb/IIIa Inhibitors 182 GP IIb/IIIa Complications 182 26. Thrombolytic Therapy 184 Agents 184 Indications 185 Complications 186 27. Bleeding and Thrombosis in Cancer Patients 188 Bleeding Syndromes 188 Cancer and Thrombosis 192 28. Bleeding and Thrombosis in Pregnancy 198 Thrombocytopenia 198 Pregnancy-Related Thrombotic Microangiopathies 199 Estrogen, Pregnancy, and Venous Thromboembolic Disease 200 Prophylaxis 204 Special Issues 205 29. Pediatric Thrombosis 207 Introduction 207 Ranges of Normal 207 Deep Venous Thrombosis and Pulmonary Embolism 207 Catheter-Related Thrombosis 207 Renal Vein Thrombosis 208 Pediatric Stroke 208 Homozygous Protein C or S Deficiency 209 Cardiac Disease 209 Pediatric Use of Antithrombotic Agents 209 Index 213 Tables Chapter 1 Table 1.1. Coagulation proteins 2 Table 1.2. Key coagulation reactions 5 Chapter 2 Table 2.1. Prothrombin time/INR 18 Table 2.2. Activated partial thromboplastin time 18 Table 2.3. Interpretions of elavated PT-INR and/or aPTT 18 Table 2.4. Four causes of elevated APTT and response to 50:50 mix 19 Table 2.5. Examples of 50:50 mixes 20 Table 2.6. Specific tests for DIC 22 Table 2.7. The thrombin time 22 Chapter 3 Table 3.1. The key questions 26 Table 3.2. Most common test results and likely (not exhaustive!) diagnoses 28 Table 3.3. Additional tests to order in bleeding patients with normal screening tests 28 Chapter 4 Table 4.1. Replacement products 31 Table 4.2. Calculation of replacement doses of factors VIII and IX 32 Table 4.3. Guidelines for factor replacement 34 Table 4.4. Therapy for inhibitors 35 Chapter 5 Table 5.1. Types of von Willebrand disease 38 Table 5.2. Testing for von Willebrand disease 39 Table 5.3. Therapy of von Willebrand disease 40 Table 5.4. Procedures 41 Chapter 6 Table 6.1. Inherited defects of platelet function 44 Table 6.2. Rare factor deficiencies 46 Chapter 7 Table 7.1. Diagnostic clues to acquired thrombocytopenia 50 Table 7.2. Initial approach to thrombocytopenia 50 Table 7.3. Differential diagnosis of isolated thrombocytopenia 51 Table 7.4. Most common drugs implicated in drug-induced thrombocytopenia 53 Chapter 8 Table 8.1. Consequences of excessive thrombin generation 61 Table 8.2. Etiologies of DIC 61 Table 8.3. Clinical presentations of DIC 62 Table 8.4. Testing for DIC 63 Table 8.5. Therapy of DIC 64 [...]... 14 .4 Five basic tests for management of massive transfusions 10 0 Table 14 .5 Management of massive transfusions 10 0 Chapter 15 Table 15 .1 Clinical probability score for deep venous thrombosis 10 3 Table 15 .2 Clinical probability score for pulmonary embolism 10 3 Chapter 16 Table 16 .1 Hypercoagulable states associated with Budd-Chiari syndrome 11 8 Table 16 .2 Priapism 11 9 Chapter 17 ... Chapter 17 Table 17 .1 Markers of hypercoagulable states 12 1 Table 17 .2 Inhertied hypercoagulable states 12 3 Table 17 .3 Evaluation of patients with hypercoagulable states 12 4 Table 17 .4 Strong and weak hypercoagulable states 12 6 Chapter 18 Table 18 .1 Renal transplants in hypercoagulable patients 12 9 Table 18 .2 Influences on plasma homocysteine levels 13 1 Table 18 .3 Therapy of... 72 Table 10 .3 Approach to bleeding cardiac surgery patient 73 Table 10 .4 Alternative anticoagulation agents for patients with HIT 74 Chapter 11 Table 11 .1 Acute therapy of ITP 78 Table 11 .2 Therapeutic options in splenectomy failures 79 Table 11 .3 Differential diagnosis of Evans syndrome 81 Chapter 12 Table 12 .1 Classifaction of thrombotic microangiopathies 83 Table 12 .2 Thrombotic... elevated homocysteine levels 13 2 Chapter 19 Table 19 .1 Diagnosis of antiphospholipid antibody syndrome 13 3 Table 19 .2 Clinical syndromes 13 5 Table 19 .3 Catastrophic antiphospholipid antibody syndrome (CAPS) 13 6 Table 19 .4 APLA diagnosis 13 7 Table 19 .5 APLA therapy 13 7 Chapter 20 Table 20 .1 Therapy of ischemic heart syndromes 14 1 Table 20.2 Acute myocardial infarction:... 15 0 Table 21. 3 Evaluation of the young patient with stroke 15 2 Table 21. 4 Blue toe syndrome (after O’Keefe) 15 4 Chapter 22 Table 22 .1 Standard heparin vs low molecular weight heparin 15 5 Table 22.2 Agents and dosing 15 6 Table 22.3 Agents for HIT 16 0 Table 22.4 Heparin induced thrombocytopenia scoring system 16 1 Chapter 23 Table 23 .1 Argatroban, hirudin and bivalirudin... purpura: Pentad 84 Table 12 .3 TTP: Therapy 86 Table 12 .4 Options to consider for refractory patients 87 Chapter 13 Table 13 .1 Non-blood product agents for bleeding disorders 91 Table 13 .2 Current uses of rVIIa (NovoSeven) 93 Chapter 14 Table 14 .1 Platelet products 95 Table 14 .2 Evaluation and management of platelet alloimmunization 97 Table 14 .3 Components in cryoprecipitate... Aspirin 17 8 Table 25.2 Thienopyridines 18 0 Table 25.3 Glycoprotien IIb/IIIa inhibitors 18 1 Chapter 26 Table 26 .1 Thrombolytic therapy 18 5 Chapter 27 Table 27 .1 Initial evaluation and management of patients with APL 18 9 Table 27.2 Coagulation defects associated with paraproteins 19 1 Chapter 28 Table 28 .1 Causes of pregnancy-related thrombocytopenia 19 8 Table 28.2... 14 3 Table 20.3 Risk factors for stroke in patients with atrial fibrillation 14 5 Table 20.4 Risk of stroke/year in patients with atrial fibrillation 14 5 Table 20.5 Risk stratification and therapy of mechanical valve patients 14 7 Table 20.6 Risk(%) for embolic events when off anticoagulation 14 7 Chapter 21 Table 21. 1 Antithrombotic therapy of cerebrovascular disease 14 9 Table 21. 2 NINDS... 16 5 Chapter 24 Table 24 .1 Nomograms for warfarin loading 16 9 Table 24.2 Maintenance warfarin adjustment nomogram 17 0 Table 24.3 Medication effects on warfarin effect 17 1 Table 24.4 Vitamin content of foods 17 2 Table 24.5 Mangagment of high INRs 17 5 Table 24.6 Management of patient anticoagulated with warfarin who needs a procedure 17 6 Chapter 25 Table 25 .1 Aspirin... side chains of the fibrin monomers Note that factor XIII is the only coagulation enzyme that is NOT a serine protease 8 Hemostasis and Thrombosis 1 Fig 1. 10 Formation of the fibrin clot Fig 1. 11 Formation of the fibrin thrombus Thrombin acts on fibrinogen to cleave fibrinopeptide A and B This forms the fibrin monomer that loosely polymerizes Factor XIII covalently bonds the fibrin monomer to form a . Vein Thrombosis 11 6 Adrenal Infarction 11 7 Budd-Chiari Syndrome 11 7 Portal Vein Thrombosis 11 8 Renal Vein Thrombosis 11 8 Visceral Vein Thrombosis 11 8 Retinal Vein Thrombosis 11 9 Priapism 11 9 17 Situations 11 0 Duration of Therapy 11 0 Prophylaxis 11 1 Who Is at Risk? 11 1 The Treatment Regimens 11 2 The Situations 11 3 16 . Thrombosis in Unusual Sites 11 6 Upper Extremity Thrombosis 11 6 Cerebral. thrombosis 10 3 Table 15 .2. Clinical probability score for pulmonary embolism 10 3 Chapter 16 Table 16 .1. Hypercoagulable states associated with Budd-Chiari syndrome 11 8 Table 16 .2. Priapism 11 9 Chapter