Hemostasis and Thrombosis - part 1 pot

98 Corrections of Defects before Procedures in Patients with Liver Disease and Other Coagulopathies .... Deep Venous Thrombosis and Pulmonary Embolism .... 102 Diagnostic Tests for Pulmo

5 Von Willebrand Disease

6 Other Inherited Bleeding

Disorders

7 Acquired Bleeding Disorders

8 Disseminated Intravascular

Coagulation

9 Liver and Renal Disease

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13 Non-Blood Product Agentsfor Bleeding Disorders

14 Transfusion Therapyand Massive Transfusions

15 Deep Venous Thrombosisand Pulmonary Embolism

16 Thrombosis in Unusual Sites

17 Hypercoagulable States

18 Acquired HypercoagulableStates

Thomas G DeLoughery, M.D.

Oregon Health Sciences University

Portland, Oregon, U.S.A.

Hemostasis and Thrombosis

VADEMECUMHemostasis and Thrombosis, 2nd EditionLANDES BIOSCIENCEGeorgetown, 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 anymeans, electronic or mechanical, including photocopy, recording, or anyinformation storage and retrieval system, without permission in writing from thepublisher

Printed in the U.S.A

Please address all inquiries to the Publisher:

Landes Bioscience, 810 S Church Street, Georgetown, Texas, U.S.A 78626Phone: 512/ 863 7762; FAX: 512/ 863 0081

To my wife Jean and my daughter Emma

Artwork by Emma DeLoughery

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

Testing 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

Treatment 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

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

Chapter 9

Table 9.1 Coagulation defects in liver disease 66

Table 9.2 Evaluation of the bleeding patient with liver disease 67

Table 9.3 Therapy of coagulation defects associated with bleeding in liver disease 67

Table 9.4 Therapy for uremic bleeding 69

Chapter 10 Table 10.1 Management of patient anticoagulated with warfarin 71

Table 10.2 Coagulation defects associated with cardiopulmonary bypass surgery 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 thrombocytopenic 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 99

Table 14.4 Five basic tests for management of massive transfusions 100

Table 14.5 Management of massive transfusions 100

Chapter 15 Table 15.1 Clinical probability score for deep venous thrombosis 103

Table 15.2 Clinical probability score for pulmonary embolism 103

Chapter 16 Table 16.1 Hypercoagulable states associated with Budd-Chiari syndrome 118

Table 16.2 Priapism 119

Chapter 17 Table 17.1 Markers of hypercoagulable states 121

Table 17.2 Inhertied hypercoagulable states 123

Table 17.3 Evaluation of patients with hypercoagulable states 124

Table 17.4 Strong and weak hypercoagulable states 126

Chapter 18

Table 18.1 Renal transplants in hypercoagulable patients 129

Table 18.2 Influences on plasma homocysteine levels 131

Table 18.3 Therapy of elevated homocysteine levels 132

Chapter 19 Table 19.1 Diagnosis of antiphospholipid antibody syndrome 133

Table 19.2 Clinical syndromes 135

Table 19.3 Catastrophic antiphospholipid antibody syndrome (CAPS) 136

Table 19.4 APLA diagnosis 137

Table 19.5 APLA therapy 137

Chapter 20 Table 20.1 Therapy of ischemic heart syndromes 141

Table 20.2 Acute myocardial infarction: Indications for warfarin anticoagulation therapy 143

Table 20.3 Risk factors for stroke in patients with atrial fibrillation 145

Table 20.4 Risk of stroke/year in patients with atrial fibrillation 145

Table 20.5 Risk stratification and therapy of mechanical valve patients 147

Table 20.6 Risk(%) for embolic events when off anticoagulation 147

Chapter 21 Table 21.1 Antithrombotic therapy of cerebrovascular disease 149

Table 21.2 NINDS trial criteria for tPA 150

Table 21.3 Evaluation of the young patient with stroke 152

Table 21.4 Blue toe syndrome (after O’Keefe) 154

Chapter 22 Table 22.1 Standard heparin vs low molecular weight heparin 155

Table 22.2 Agents and dosing 156

Table 22.3 Agents for HIT 160

Table 22.4 Heparin induced thrombocytopenia scoring system 161

Chapter 23 Table 23.1 Argatroban, hirudin and bivalirudin 165

Chapter 24 Table 24.1 Nomograms for warfarin loading 169

Table 24.2 Maintenance warfarin adjustment nomogram 170

Table 24.3 Medication effects on warfarin effect 171

Table 24.4 Vitamin content of foods 172

Table 24.5 Mangagment of high INRs 175

Table 24.6 Management of patient anticoagulated with warfarin who needs a procedure 176

Chapter 25 Table 25.1 Aspirin 178

Table 25.2 Thienopyridines 180

Table 25.3 Glycoprotien IIb/IIIa inhibitors 181

Chapter 26

Table 26.1 Thrombolytic therapy 185

Chapter 27 Table 27.1 Initial evaluation and management of patients with APL 189

Table 27.2 Coagulation defects associated with paraproteins 191

Chapter 28 Table 28.1 Causes of pregnancy-related thrombocytopenia 198

Table 28.2 Therapy of ITP in pregnancy 199

Table 28.3 Estimated fetal exposure 202

Table 28.4 Therapy of deep venous thrombosis in pregnancy 203

Table 28.5 Prophylaxis 204

Chapter 29 Table 29.1 Pediatric dosing of hepairn and LMWH heparin 210

Table 29.2 Pedatric dosing of warfarin 210

Table 29.3 Pediatric dosing of thrombolytic therapy 211