Essential Guide to Blood Coagulation

Edited by Jovan P. Antovic and Margareta Blombäck Department of Molecular Medicine and Surgery, Coagulation Research, Karolinska Institutet; Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden

List of contributors, x

Preface, xii

Abbreviations, xiii

PART 1: GENERAL HEMOSTASIS

1 Schematic presentation of the hemostatic system, 3
Nils Egberg

2 Proposals for sampling instructions, 6
Margareta Blombäck and Nils Egberg

Points to note prior to sampling, 6

Sampling time and patient preparation, 7

Referrals for coagulation analyses, 8

Sampling, 8

Technique, 9

For DNA investigation (genetic analyses), 10

3 Laboratory investigations, 11
Jovan P. Antovic, Liselotte Onelöv, and Nils Egberg

Nomenclature, 11

Reference intervals for laboratory investigations, 13

Screening analyses, 13

Special analyses, 20

Markers of coagulation activation (hypercoagulation markers), 29

DNA analyses, 29

Global hemostatic assays and bedside methods, 31

Useful components in research studies, 32

Platelet-activating predictors, 35

PART 2: BLEEDING DISORDERS

4 Hereditary bleeding disorders, 41
Margareta Holmström and Lars Göran Lundberg

General remarks about hemophilia A and B, 41

General remarks about von Willebrand disease, 42

Factor concentrates used for treatment of hemophilia A and B and VWD in Sweden in 2012, 43

Treatment strategy in severe forms of hemophilia and VWD, 44

Recommendations for desired initial plasma concentrations at different types of bleedings, 45

Surgery in patients with bleeding disorders, 47

Tooth extraction in a hemophilia patient, 47

Caution in patients with bleeding disorders, 48

Treatment principles for different types of bleeding disorders (severe, moderate, and milder forms of hemostatic defects), 49

Rare bleeding disorders, 51

Blood sampling in bleeding disorders, 54

Bleeding risk charts, 54

5 Critical bleeding, 56
Maria Bruzelius, Anna Ågren, and Hans Johnsson

Introduction, 56

Definition of massive bleeding, 56

Transfusion coagulopathy, 56

Recommendations to obtain optimal hemostasis, 57

Choice of plasma, 58

Local procedures, 59

Additional treatment, 59

Fibrinogen concentrate, 59

Prothrombin-complex concentrate (PCC), 59

Recombinant factor VIIa, 59

Concentrates of other coagulation factors, 60

Cryoprecipitates, 60

Tranexamic acid, 60

Desmopressin, 60

Local hemostatic drugs, 60

Complicating factors, 61

Ongoing treatment with antiplatelet, and anticoagulant drugs, 61

6 Investigation of increased bleeding tendency, 62
Margareta Holmström and Lars Göran Lundberg

Introduction, 62

Diagnosis, 62

Reasons for pathologic screening analyses and further actions, 64

Causes of thrombocytopenia, 64

Causes of prolonged activated partial thromboplastin time, 65

Causes of elevated PT(INR), 66

Investigation of bleeding tendency: practical aspects, 66

PART 3: THROMBOEMBOLIC DISORDERS

7 Venous thrombosis and pulmonary embolism, 71
Anders Carlsson

Introduction, 71

Venous thrombosis, 72

Pulmonary embolism, 75

Primary prophylaxis against VTE, 91

8 Investigations of thromboembolic tendency, 94
Margareta Holmström

Introduction, 94

Venous thromboembolism, 95

Arterial thromboembolism, 96

Disseminated intravascular coagulation, 96

9 Heart disease, 97
Håkan Wallen and Rickard Linder

Ischemic heart disease, 97

Atrial fibrillation, 102

Cardiac valve prosthesis, 103

New oral anticoagulants in the treatment of heart disease, 104

10 Antiplatelet drug therapy and reversal of its effects, 105
Håkan Wallen, Hans Johnsson, and Bo-Michael Bellander

Introduction, 105

ASA, 105

ADP (P2Y12) receptor antagonists, 106

GPIIb/IIIa receptor antagonists, 106

Phosphodiesterase inhibitors and other antiplatelet compounds, 108

Combined antithrombotic treatment, 108

Benefi t–risk assessment, 108

Platelet transfusion, 109

11 New oral anticoagulants: Focus on currently approved oral factor Xa and Thrombin inhibitors, 111
Rickard E. Malmström and Hans Johnsson

Clinical pharmacology of NOACs, 111

Possibility of and need for therapeutic monitoring of NOACs, 114

Clinical aspects of NOACs, 114

Results of clinical trials, 116

Some characteristics of the individual NOACs, 118

Considerations to be taken when using NOACs in some emergency situations

12 Stroke and transient ischemic attack, 121
Nils Wahlgren and Mia von Euler

Antithrombotic secondary stroke prevention, 121

Atrial fibrillation and TIA or stroke, 122

Thrombolysis in stroke, 122

Cerebral venous thrombosis and dissection of precerebral arteries, 123

Recurrent TIA, 124

Prophylactic treatment against DVT and PE, 124

13 Peripheral artery surgery, 125
Jesper Swedenborg

Prophylaxis against reocclusion in peripheral vascular surgery or percutaneous transluminal angioplasty (PTA), 125

Peri- and postoperative treatment, 125

Thrombolysis in acute ischemia, 126

PART 4: SPECIAL HEMOSTASIS

14 Hemostasis in obstetrics and gynecology, 129
Katarina Bremme

Introduction, 129

Thrombosis during pregnancy, 131

Heart disease: treatment of women with mechanical heart valve prostheses, 139

Thromboprophylaxis in obstetrics and gynecology, 140

Blood sampling in children of women with severe forms of thrombophilia, 148

Obstetric epidural/spinal analgesia (anesthesia), 148

Complications during pregnancy, 150

Postpartum bleeding, 155

Thromboprophylaxis in legal and spontaneous abortions, 156

Thromboprophylaxis in gynecologic surgery, 156

Investigation prior to artificial insemination (IVF), 160

Investigation in repeated miscarriages, 160

Investigation in menorrhagia (for treatment see Chapter 4), 161

15 Hemostasis in children, 162
Susanna Ranta and Pia Petrini

Introduction, 162

Bleeding disorders in children, 166

Thromboembolic disorders in children, 172

16 Emergency conditions associated with coagulation: DIC, HIT and TTP/HUS, 182
Jovan P. Antovic and Margareta Holmström

Disseminated intravascular coagulation, 182

Heparin-induced thrombocytopenia, 188

Thrombotic microangiopathies, 190

Index, 191