Inherited Bleeding Disorders in Women, 2nd Edition

The essential guide for understanding and treating women with inherited bleeding disorders, revised and updated

Now in its second edition, Inherited Bleeding Disorders in Women includes the most recent developments and research in the field. This important guide offers the most current information available for the effective management of these complex and difficult to diagnose disorders. Treating women with inherited bleeding disorders can be challenging and requires close collaboration among practitioners in different specialties.

This important guide is written by a team of international experts who offer advice and practical suggestions for treating women with inherited bleeding disorders. Inherited Bleeding Disorders in Women comprehensively covers obstetric and gynecological issues for carriers of hemophilia, women with von Willebrand disease, rare bleeding disorders and inherited platelet disorders. This important resource:

• Offers an updated guide for hematologists, obstetricans and gynecologists and other clinicians treating women with inherited bleeding disorders
• Includes information for treating both common and rare bleeding disorders
• Contains the most recent developments and advances in the field for the treatment and management of inherited bleeding disorders in women
• Presents information from noted experts in the field
• Offers a multidisciplinary approach to the topic

Written for hematologists, obstetricians and gynecologists and other clinicians working with women, Inherited Bleeding Disorders in Women has been fully revised and updated and continues to serve as a trusted guide for the management and treatment of women with inherited bleeding disorders.

Table of contents

Preface to Second Edition ix

Preface to First Edition xi

List of Contributors xiii

1 Hematological Assessment of a Patient with an Inherited Bleeding Disorder 1 
Sue Pavord and Henna Wong

1.1 Introduction 1

1.2 Normal Hemostasis 1

1.3 Defects of Hemostasis 5

1.4 Clinical Presentation of Bleeding 5

1.5 Diagnosis 6

1.6 Approach to a Female with a Bleeding History 6

1.7 Summary 10

References 11

2 Bleeding Assessment Tools 13
Sarah H. O’Brien and Paula D. James

2.1 Introduction 13

2.2 Evolution of Vicenza‐Based Bleeding Assessment Tools 13

2.3 Women’s Studies Using Vincenza‐Based Bleeding Tools 22

2.4 Tools to Evaluate Menstrual Blood Loss 23

2.5 Young Women’s Hematology and Bleeding Assessment Tools 25

2.6 Clinical Utility of Bleeding Assessment Tools 25

2.7 Conclusion 26

References 27

3 Physiology of Menstruation 29
Jane J. Reavey, Jacqueline A. Maybin, and Hilary O.D. Critchley

3.1 Introduction 29

3.2 Normal Menstruation 29

3.3 Neuroendocrine Hormones 30

3.4 Menarche 31

3.5 Ovarian Follicle Development and Endocrine Function 31

3.6 Endometrium 33

3.7 Secretory Phase 34

3.8 Menstruation 35

3.9 Control of Bleeding 37

3.10 Endometrial Repair 38

3.11 Proliferative Phase 40

3.12 Summary 40

References 41

4 Gynecology 45
Joanna S. Davies and Rezan A. Kadir

4.1 Introduction 45

4.2 Heavy Menstrual Bleeding 48

4.3 Management of Acute Episodes of Heavy Menstrual Bleeding 58

4.4 Ovulation Bleeding 59

4.5 Endometriosis 59

4.6 Other Gynecological Conditions 60

4.7 Conclusion 61

References 61

5 Carriers of Hemophilia A and Hemophilia B 65
Roseline d’Oiron

5.1 Inheritance 65

5.2 Screening for the Genetic Status of Carriers of Hemophilia 65

5.3 Confusion Between Genetic and Coagulation Testing 66

5.4 When to Perform Genetic Testing 67

5.5 What Reasons might Contribute to Delayed Genetic Diagnosis of Carriership? 68

5.6 Bleeding Disorders in Carriers of Hemophilia 68

5.7 Quality of Life of Carriers of Hemophilia 73

5.8 Carriers of Hemophilia A and B and Pregnancy 73

5.9 How to Improve Care for Carriers of Hemophilia 77

References 79

6 Von Willebrand Disease 83
Carolyn M. Millar

6.1 Introduction 83

6.2 Structure and Function of Von Willebrand Factor 83

6.3 Von Willebrand Factor Levels and Prevalence of Von Willebrand Disease 84

6.4 VWF Levels, the Menstrual Cycle and Pregnancy 84

6.5 Von Willebrand Disease Classification and Inheritance 85

6.6 Clinical Presentation 87

6.7 Menorrhagia and Postpartum Hemorrhage 87

6.8 Diagnosis and Laboratory Testing 88

6.9 Management of Von Willebrand Disease 90

6.10 Management of Gynecological Bleeding 91

6.11 Obstetric Management of Von Willebrand Disease 92

6.12 Neonatal Management 94

6.13 Cases 94

References 96

7 Factor XI Deficiency 101
Bethan Myers and Rezan A. Kadir

7.1 Factor XI Structure and Function in Coagulation 101

7.2 Incidence and Inheritance of Factor XI Deficiency 101

7.3 Bleeding Manifestations and Diagnosis of Factor XI Deficiency 103

7.4 Factor XI Deficiency and Gynecological Issues 103

7.5 Factor XI Deficiency and Pregnancy 105

7.6 Neuroaxial Analgesia and Anesthesia 108

7.7 Management of Postpartum Period 108

7.8 Treatment Options 109

7.9 Neonatal Bleeding 111

7.10 Conclusions and Recommendations 111

References 112

8 Rare Bleeding Disorders 117
Danijela Mikovic, Marzia Menegatti, and Flora Peyvandi

8.1 Introduction 117

8.2 Clinical Symptoms 118

8.3 Gynecological and Obstetrical Manifestations in Women with Rare Bleeding Disorders 119

8.4 Laboratory Diagnosis 122

8.5 Differential Diagnosis in Women with Menorrhagia 123

8.6 Treatment 124

8.7 Conclusion 128

References 129

9 Inherited Platelet Defects 133
Mike Makris and Clare Samuelson

9.1 Introduction 133

9.2 Normal Platelet Function 133

9.3 Presentation 136

9.4 Investigation 137

9.5 Syndromic and Non‐Syndromic Inherited Platelet Disorders with Recognized Causative Genes 143

9.6 Prenatal Diagnosis 143

9.7 Management 144

9.8 Future Directions 147

9.9 Case Histories 147

9.10 Conclusion 148

References 149

10 Genetic and Laboratory Diagnosis 153
Anne C. Goodeve

10.1 Introduction 153

10.2 Phenotypic Analysis of Hemophilia A 154

10.3 Phenotypic Analysis of Hemophilia B 156

10.4 Phenotypic Analysis of von Willebrand Disease 157

10.5 Phenotypic Analysis of Inherited Bleeding Disorders 157

10.6 Genetic Analysis of Hemophilia A 160

10.7 Genetic Analysis of Hemophilia B 162

10.8 Genetic Analysis of von Willebrand Disease 163

10.9 Guidelines 164

10.10 Summary 164

References 164

11 Antenatal Diagnosis 167
Rezan A. Kadir, Irena Hudecova, and Claudia Chi

11.1 Introduction 167

11.2 Genetic Counseling 167

11.3 Prenatal Diagnosis 170

11.4 Prenatal Diagnosis of Hemophilia 177

11.5 Prenatal Diagnosis of von Willebrand Disease 180

11.6 Prenatal Diagnosis of Rare Bleeding Disorders 180

11.7 Preimplantation Genetic Diagnosis 181

11.8 Views about and Experiences of Prenatal Diagnosis of Women in Families Affected with Inherited Bleeding Disorders 183

11.9 Termination of Pregnancy 185

References 186

12 Analgesia and Anesthesia for Pregnant Women with Inherited Bleeding Disorders 191
Anne‐Sophie Bouthors, Adrian England, and Rezan A. Kadir

12.1 Introduction 191

12.2 Non‐Pharmacological Methods 192

12.3 Pharmacological Methods 192

12.4 Conclusion 201

References 202

13 The Newborn 205
Manuel Carcao and Vanessa Bouskill

13.1 Introduction 205

13.2 Developmental Hemostasis 205

13.3 Laboratory Hemostatic Evaluation of the Neonate 208

13.4 When to Suspect a Congenital Bleeding Disorder in a Newborn 209

13.5 Congenital Bleeding Disorders and Their Presentation in Newborns 213

13.6 Management of Bleeding in Neonates with Congenital Bleeding Disorders 218

13.7 Conclusion 221

References 222

14 Women with Inherited Bleeding Disorders in Different Cultural Settings 225
Tahira Zafar, Jameela Sathar, Ali T. Taher, Fadi G. Mirza, and Christine A. Lee

14.1 Introduction 225

14.2 Pakistan 225

14.3 Malaysia 227

14.4 Lebanon 229

14.5 Discussion 231

References 232

Index 235