Hemostasis and Thrombosis (eBook)

Contents 5
Contributors 7
1: Basics of Coagulation 8
Formation of Fibrin 8
The Old Pathways 8
The Players 9
“Quaternary Complex” 10
Initiation of Coagulation 10
Thrombin 11
Fibrin Formation 11
Propagation 12
Fibrinolysis 12
Fibrinolytic Proteins 12
Fibrinolysis: The Process 13
Platelet Production and Life Span 13
Thrombopoietin (TPO) 13
Functions of Platelets 14
Platelet Adhesion 14
About von Willebrand Factor 14
Summary of Platelet Adhesion 14
Platelet Storage 14
Platelet Aggregation 14
Platelet Surface 15
Natural Anticoagulants 15
Suggested Reading 16
2: Tests of Hemostasis and Thrombosis 17
Bleeding Disorders 17
Bleeding History 17
Specific Assays for Bleeding Disorders (Tables 2.1, 2.2, and 2.3) 17
Prothrombin Time (PT) 17
Activated Partial Thromboplastin Time (aPTT) 18
Specific Factor Assays 19
Platelet Function 20
Bleeding Time 20
Platelet Function Analysis 20
Flow Cytometry 20
Specific Platelet Studies 20
Test for DIC 21
Thromboelastography (TEG) (Table 2.8) 22
Thrombotic Disorder 22
Tests for APLA 23
Specific Assays 23
Hypercoagulable States 24
Suggested Reading 24
3: Bleeding Disorders: A General Approach 25
Suggested Reading 27
4: Hemophilia 28
Introduction 28
Pathophysiology and Classification 28
Clinical Presentation and Symptoms 29
Hemarthrosis 29
Intramuscular Hematomas 29
Cerebral Hemorrhage 29
Diagnosis 29
Therapy 30
Hemophilia A (Factor VIII Deficiency) 30
Hemophilia B (Factor IX Deficiency) 31
Prophylactic Factor Use 32
Emicizumab 32
Guidelines for Specific Types of Bleeds (Table 4.3) 33
Surgery in the Patient with Hemophilia 34
Inhibitors 34
Management of Factor Inhibitors 35
Future Therapy 36
Conclusions 36
Suggested Reading 36
5: Von Willebrand Disease 37
Introduction 37
Pathogenesis and Classification 37
Signs and Symptoms 38
Testing 39
Therapy 40
Therapy by vWD Subtype 41
Pregnancy 42
Suggested Reading 42
6: Other Inherited Bleeding Disorders 43
Platelet Defects 43
Introduction 43
Defective Platelet Function 43
Congenital Thrombocytopenia 44
Named Platelet Disorders 44
Platelet Function Disorders with Normal Platelet Numbers 44
Thrombocytopenia (Large Platelets) 44
Thrombocytopenia (Normal-Sized Platelets) 45
Thrombocytopenia (Small Platelets) 45
Less Common Coagulation Disorder 45
Suggested Reading 47
7: Acquired Bleeding Disorders 48
Thrombocytopenia 48
Diagnostic Approach (Table 7.2) 49
Etiologies of Thrombocytopenia (Table 7.3) 49
Decreased Production 49
Sequestration 50
Increased Destruction: Immune 50
Dysfunctional Platelets 51
Acquired Coagulation Factor Deficiency 52
Vitamin K Deficiency 53
Antibiotics 53
Malnutrition 54
Rat Poison/“Superwarfarin” 54
Specific Acquired Factor Deficiencies 54
Acquired Von Willebrand Disease 56
Suggested Reading 57
8: Disseminated Intravascular Coagulation 58
Pathogenesis 58
Etiology 59
Clinical Presentation (Table 8.3) 60
Diagnosis 60
Suggested Reading 62
9: Liver and Renal Disease 63
Liver Disease 63
Pathogenesis of Defects 63
Evaluation and Treatment of Coagulation Defects in Liver Disease 64
Preparation for Surgery 65
Liver Transplantation 65
Uremia 66
Pathogenesis 66
Evaluation 66
Therapy (Table 9.4) 66
Suggested Reading 67
10: Cardiac Bypass and Ventricular Assist Devices/ECMO 68
Introduction 68
Preoperative Coagulation Defects 68
Cardiopulmonary Bypass 69
Prevention and Therapy 69
Approach to the Bleeding Bypass Patient (Table 10.3) 70
Ventricular Assist Devices (VADs) 70
Extracorporeal Membrane Oxygenation (ECMO) 71
Special Situations 71
Suggested Reading 72
11: Immune Thrombocytopenia 73
Introduction 73
Pathogenesis and Epidemiology 73
Symptoms 73
Diagnosis 74
Therapy 74
Initial Therapy (Table 11.1) 74
Chronic Therapies (Table 11.2) 75
Splenectomy 75
Rituximab 75
Thrombopoietin (TPO)-Mimetics 76
Romiplostim 76
Eltrombopag 76
Clinical Use of TPO-Mimetics 76
Fostamatinib 76
Other Options 76
A Practical Approach to the Refractory Patient 77
Special Situations 77
Surgery 77
Pregnancy 78
Pediatric Patients 78
Evans Syndrome 78
Suggested Reading 79
12: Thrombotic Microangiopathy (TTP/HUS) 80
Introduction 80
Classification 80
Classic Thrombotic Thrombocytopenic Purpura (TTP) 80
Clinical Presentation 80
Neurological 81
Hematologic 81
Renal 81
Gastrointestinal 81
Pulmonary 81
Cardiac 81
Pathogenesis 82
Differential Diagnosis 82
Therapy (Table 12.3) 82
Refractory Patients (Table 12.4) 83
Prevention of Recurrences 83
Role of Rituximab in TTP 84
Role of ADAMTS13 Levels 84
Hemolytic-Uremic Syndrome (HUS) 84
Typical HUS 84
Atypical HUS 84
Pregnancy-Related TM 85
Pregnancy-Related TTP 85
Postpartum HUS 85
Therapy-Related HUS 85
Calcineurin Inhibitor HUS 86
Stem Cell Transplant TM 86
Drug-Related TM 86
Suggested Reading 87
13: Non-blood Product Agents for Bleeding Disorders 88
Desmopressin 88
Aminocaproic Acid and Tranexamic Acid 89
Aprotinin 90
Conjugated Estrogens 90
Recombinant VIIa (rVIIa) 90
Suggested Reading 90
14: Transfusion Therapy and Massive Transfusions 91
Platelets 91
Management of the Platelet-Refractory Patient 92
Fresh Frozen Plasma (FFP) 93
Cryoprecipitate 93
Corrections of Defects Before Procedures in Patients with Liver Disease and Other Coagulopathies 94
Massive Transfusions 94
Managing Massive Transfusions 94
Complications 96
Suggested Reading 96
15: Deep Venous Thrombosis and Pulmonary Embolism 97
Natural History 97
Diagnostic Tests for Pulmonary Embolism and Deep Venous Thrombosis 97
Diagnostic Approach to DVT or PE 99
Immediate Therapy 100
Thrombolytic Therapy 100
Anticoagulant Treatment of Venous Thromboembolism 101
Unfractionated Heparin 101
Low Molecular Weight Heparin 102
Fondaparinux 102
Warfarin 102
Direct Oral Anticoagulants 102
Special Situations 103
In Patients with Cancer 103
In the Pregnant Patient 103
Calf and Muscular Vein Thrombosis 103
Superficial Venous Thrombosis 103
“Incidental PE” 103
Subsegmental PE 103
Duration of Therapy (Table 15.5) 103
Prophylaxis of Venous Thromboembolic Disease 104
Overview 104
Etiology of Surgical Hypercoagulable States 104
The Need for Deep Venous Thrombosis Prophylaxis in Surgery 105
Who Is at Risk of Thrombosis? 105
The Prophylactic Regimens 105
The Situations 106
Low-Risk Patients 106
Medium-Risk Patients 106
High-Risk (Non-orthopedic) Patients 106
Knee Surgery 106
Elective Hip Surgery 106
Hip Fractures 107
Trauma 107
Neurosurgery 107
Medical Patients 107
In Pregnancy 107
Suggested Reading 108
16: Thrombosis in Unusual Sites 109
Upper Extremity Thrombosis 109
Cerebral Vein Thrombosis 109
Adrenal Infarction 110
Budd-Chiari Syndrome 110
Renal Vein Thrombosis 111
Portal Vein Thrombosis 111
Mesenteric Vein Thrombosis 111
Retinal Vein Thrombosis 111
Priapism (Table 16.2) 112
Suggested Reading 112
17: Inherited Thrombophilias 113
When to Suspect a Thrombophilia (Table 17.1) 113
Why Diagnose Thrombophilias? 113
Approach to the Patient Suspected of Having a Thrombophilia 114
Is the Thrombosis Arterial or Venous? 114
Where Is the Site of Thrombosis? 114
What Is the Age of the Patient? 114
Were or Are There Any Associated Risk Factors for Thrombosis? 114
Is There a Family History of Thrombosis? 114
Screening Family Members 115
The Congenital Thrombophilias (Table 17.2) 115
Suggested Evaluation in Patients with Venous Thrombosis 116
Testing 117
Therapy 117
Suggested Reading 117
18: Acquired Thrombophilias 118
Inflammatory Bowel Disease 118
Surgery 119
Nephrotic Syndrome and Other Renal Disease 119
Paroxysmal Nocturnal Hemoglobinuria (PNH) 120
Behçet’s Disease 120
Hemolytic Disorders 121
Air Travel 121
Suggested Reading 121
19: Antiphospholipid Antibody Syndrome 122
Antiphospholipid Antibodies (APLA) 122
Definitions 122
Who Gets APLA? 123
APLA: Clinical Associations 123
Catastrophic APLA (CAPS) 124
Diagnostic Approach to APLA 125
Therapy 126
Difficulties in Monitoring Anticoagulation 126
Suggested Reading 127
20: Antithrombotic Therapy for Cardiac Disease 128
Cardiac Disease 128
Ischemic Heart Disease 128
Primary Prevention 128
Stable Angina 128
Non-ST Elevation MI (NSTEMI) 129
Acute Myocardial Infarction: Acute Therapy 130
Thrombolytic Therapy 130
Choice of Drug and Dosing 130
Adjuvant Therapy to Thrombolytic Therapy 130
STEMI: Long-Term Antithrombotic Therapy 131
CABG 131
Coronary Stenting 131
Stents and Anticoagulation 131
Evaluation of the Young Patient with Acute Myocardial Infarction 132
Prevention of Embolism 132
Atrial Fibrillation 132
Atrial Fibrillation: Special Situations 133
Rheumatic Valve Disease 133
Mechanical Prosthetic Heart Valves 134
Bioprosthetic Heart Valves 134
Chronic Heart Failure 134
Suggested Reading 135
21: Stroke and Peripheral Vascular Disease 136
Stroke 136
Acute Stroke 136
Transient Ischemic Attacks 138
Patients with Recurrent Strokes 138
Patent Foramen Ovale and Stroke 138
Stroke in Young Patients 139
Peripheral Vascular Disease 139
Acute Ischemia 139
Antithrombotic Therapy for Peripheral Vascular Disease 140
Suggested Reading 141
22: Heparins and Heparin-Induced Thrombocytopenia 142
Antithrombotic Use of Standard Heparin 142
Antithrombotic Use of Low-Molecular-Weight Heparin 143
Antithrombotic Use of Pentasaccharides 144
Special Problems 144
Complications of Heparin 145
Heparin-Induced Thrombocytopenia (HIT) 145
Suggested Reading 147
23: Other Parenteral Anticoagulants 148
Introduction 148
Danaparoid 148
Direct Thrombin Inhibitors 148
Argatroban 149
Bivalirudin 149
Hirudin 149
Argatroban 149
For PCI 149
Bivalirudin 149
Danaparoid 150
Desirudin 150
Hirudin 150
Suggested Reading 150
24: Direct Oral Anticoagulants 151
Introduction 151
General Considerations 152
Thrombin Inhibitor: Dabigatran 152
Factor Xa Inhibitors 153
Apixaban 153
Betrixaban 153
Edoxaban 154
Rivaroxaban 154
Diseases Where the Direct Oral Anticoagulants Have Been Studied 154
Atrial Fibrillation 154
Prevention of Venous Thrombosis 154
Treatment of Venous Thrombosis 154
Cancer Patients 155
Acute Coronary Syndrome and Coronary Arterty Disease 155
Monitoring 155
Suggested Reading 155
25: Warfarin 156
Therapeutic Range of the INR 158
Complications of Warfarin Therapy 159
Addition to Antiplatelet Agents to Warfarin 160
Warfarin Resistance and Unstable INRS 160
Management of High INRs and Bleeding 161
When to Restart Anticoagulation After Serious Bleeding? 162
Temporary Cessation of Warfarin for Procedures 162
Suggested Reading 163
26: Antiplatelet Agents 164
Aspirin 164
Platelet P2Y12 Receptor Antagonists 165
Clopidogrel 165
Prasugrel 166
Ticagrelor 166
Cangrelor 166
Other Platelet Antagonists 166
Dipyridamole 166
Vorapaxar 166
Glycoprotein IIb/IIIa Inhibitors 167
Abciximab 167
Tirofiban 167
Eptifibatide 167
Current Role of GP IIb/IIIa Inhibitors 167
GP IIb/IIIa Complications 167
Aspirin 168
Thienopyridines 168
Clopidogrel 168
Prasugrel 168
Reversible P2Y12 Inhibitors 168
Ticagrelor 168
Cangrelor 168
Other Antiplatelet Agents 168
Sustained Release Dipyridamole/Aspirin 168
Vorapaxar (Thrombin Receptor inhibitor) 169
Glycoprotein IIb/IIIa Inhibitors 169
Abciximab 169
Tirofiban 169
Eptifibatide 169
Suggested Reading (See Also Chap. 20) 169
27: Thrombolytic Therapy 170
Agents 170
Indications 171
Myocardial Infarction 171
Stroke 171
Deep Venous Thrombosis/Pulmonary Embolism 171
Complications 172
Thrombolytic Therapy 172
Suggested Reading 172
28: Clinical Dilemmas in Anticoagulation: Extremes of Weight, Renal Disease, Recent Bleeding, and Surgery 173
Extremes of Weight 173
Renal Disease 173
Elderly Patients and Those at Risk of Falling 174
Liver Disease 175
Patients with Recent Bleeding 175
Reversal of Antithrombotic Agents (Table 28.2) 175
Antithrombotic Therapy and Surgery 176
Antiplatelet Agents 177
Anticoagulants 177
Heparins 177
Warfarin 177
Direct Oral Anticoagulants 178
Suggested Reading 178
29: Bleeding and Thrombosis in Cancer Patients 180
Bleeding Syndromes 180
Acute Promyelocytic Leukemia (APL) 180
Etiology 180
Diagnosis 181
Therapy 181
Bleeding in Other Leukemias and Myelodysplastic Syndromes 182
Myeloproliferative Syndromes 182
Dysproteinemias 182
Acquired Factor Deficiencies 183
Cancer and Thrombosis 184
Myeloproliferative Syndromes 185
Therapy of Thrombosis in Myeloproliferative Syndromes 185
Paroxysmal Nocturnal Hemoglobinuria (PNH) 186
Catheter Thrombosis 186
Chemotherapeutic Agents 187
Bone Marrow Transplantation 188
Suggested Reading 188
30: Hemostasis and Thrombosis in Pregnancy 189
Thrombocytopenia in Pregnancy 189
Gestational Thrombocytopenia 189
Immune Thrombocytopenic Purpura 189
Treatment of ITP in Pregnancy 190
Thrombotic Microangiopathy 190
Preeclampsia/HELLP 190
Thrombotic Thrombocytopenic Purpura 190
Atypical Hemolytic Uremic Syndrome 190
Acute Fatty Liver of Pregnancy 191
Hemorrhage in Pregnancy 191
Postpartum Hemorrhage 191
Delayed Postpartum Hemorrhage 191
Von Willebrand Disease 191
Hemophilia 192
Rare Bleeding Disorders 192
Thrombosis in Pregnancy 193
Acute Venous Thromboembolism 193
Diagnosis of Acute VTE 193
Treatment of Acute VTE 193
Management of Prior VTE 194
Postpartum Prophylaxis 194
Antepartum Prophylaxis 194
Congenital Thrombophilias 194
Antepartum and Postpartum Prophylaxis 194
Screening for Congenital Thrombophilias 195
Acquired Thrombophilia: Antiphospholipid Syndrome 195
Diagnosis of APS 195
Antepartum and Postpartum Management of APS 195
Suggested Reading 195
31: Hemorrhage and Thrombosis in Women 199
Hemorrhagic Complications 199
Heavy Menstrual Bleeding 199
Laboratory Workup 199
Gynecologic Workup 200
Management 200
Adjunctive Therapies 201
Special Populations 202
Thrombotic Complications 202
Estrogen-Associated Thrombosis 202
Pathophysiology 203
Management 203
Use of Estrogen Therapies in Patients with a History of Thrombosis 203
Contraception 203
Hormone Replacement Therapy 204
Summary 204
Suggested Reading 205
32: Pediatric Thrombosis 206
Introduction 206
Ranges of Normal 206
Deep Venous Thrombosis and Pulmonary Embolism 207
Catheter-Related Thrombosis 208
Abdominal Venous Thrombosis 209
Pediatric Stroke 209
Homozygous Protein C or S Deficiency 211
Pediatric Use of Antithrombotic Agents 211
Antiplatelet Therapy 211
Heparin and Heparin-Induced Thrombocytopenia 211
Low Molecular Weight Heparin 212
Warfarin 212
Thrombolytic Therapy 212
New Oral Anticoagulants 213
Suggested Reading 213
Index 214