Textbook of Hemophilia

Christine A. Lee, MA, MD, DSc, FRCP, FRCPath, Emeritus Professor of Haemophilia, University of London; Honorary Consultant Haematologist, Oxford Haemophilia & Thrombosis Centre, Oxford, UK. Erik E. Berntorp, MD, PhD, Professor of Hemophilia, Lund University; Director, Department of Coagulation Disorders, Malmo University Hospital, Malmo, Sweden. W. Keith Hoots, MD, Professor of Pediatrics, University of Texas M.D. Anderson Cancer Center; Professor of Pediatrics and Internal Medicine, University of Texas Medical School at Houston; Medical Director, Gulf States Hemophilia and Thrombophilia Center, Houston, Texas, USA.

Contributors ix

Historical introduction xv
Christine A. Lee

Part I: Introduction

1 Overview of hemostasis 3
Kathleen Brummel Ziedins and Kenneth G. Mann

2 Cellular processing of factor VIII and factor IX 9
Michael U. Callaghan and Randal J. Kaufman

Part II: Hemophilia A

3 Molecular basis of hemophilia A 23
Geoffrey Kemball-Cook and Keith Gomez

4 Prophylaxis 33
Kathelijn Fischer and H. Marijke van den Berg

Part III: Inhibitors to Factor VIII

5 Inhibitors to factor VIII: immunology 43
Jean-Marie R. Saint-Remy and Marc G. Jacquemin

6 Genetic and Environmental Risk Factors for Factor VIII inhibitor development 48
Jan Astermark

7 Epidemiology of inhibitors in hemophilia 53
Alfonso Iorio

8 Inhibitors to factor VIII: mild and moderate hemophilia 59
Kathelijne Peerlinck and Marc Jacquemin

9 Inhibitors to factor VIII/IX: immune tolerance 64
Donna M. DiMichele

10 Prophylaxis in inhibitor patients 72
Alessandro Gringeri

11 Inhibitors to factor VIII: treatment of acute bleeds 78
Claude Negrier

Part IV: Acquired Hemophilia

12 Acquired inhibitors to factor VIII 87
Craig M. Kessler

Part V: Hemophilia B

13 Hemophilia B: molecular basis 97
Keith Gomez and Pratima Chowdary

14 Factor IX inhibitors in hemophilia B 103
Meera B. Chitlur and Jeanne M. Lusher

15 Treatment of inhibitors in hemophilia B 107
Anand Tandra and Amy D. Shapiro

Part VI: Pharmacokinetics of Factors VIII and IX

16 Pharmacokinetics 117
Sven Björkman

17 Individualized dosing 123
Peter W. Collins

Part VII: Hemophilia: Birth to Old Age

18 Neonate with hemophilia 131
Angela E. Thomas and Elizabeth A. Chalmers

19 Work-up of a bleeding child 138
Manuel D. Carcao and Victor S. Blanchette

20 Care of the child with hemophilia 145
Rolf C.R. Ljung

21 Hemophilia in adolescence 150
Pia Petrini

22 Old age medicine and hemophilia 154
Evelien P. Mauser-Bunschoten and Roger E.G. Schutgens

Part VIII: Products Used to Treat Hemophilia

23 Products used to treat hemophilia: recombinant products 165
Midori Shima and Akira Yoshioka

24 Products used to treat hemophilia: plasma-derived coagulation factor concentrates 174
Paul L.F. Giangrande

25 Products used to treat hemophilia: dosing 180
Miguel A. Escobar

26 Products used to treat hemophilia: regulation 185
Albert Farrugia

27 New drugs in the pipeline: from concept to clinic 192
Leonard A. Valentino

Part IX: Surgical management

28 General surgical management of patients with hemophilia 199
Cindy Leissinger and Rebecca Kruse-Jarres

29 Continuous infusion of coagulation products in hemophilia 204
Angelika Batorova and Uri Martinowitz

30 Surgery in inhibitor patients 213
Pål Andrè Holme

Part X: Musculoskeletal

31 Joint replacement in patients with hemophilia 221
Nicholas Goddard

32 Medical synovectomy (synoviorthesis) in hemophilia: radiosynovectomy and chemical synovectomy 228
E. Carlos Rodriguez-Merchan

33 Pseudotumors in patients with hemophilia 233
Michael Heim and Uri Martinowitz

34 Imaging modalities for assessment of hemophilic arthropathy 237
Andrea S. Doria and Björn Lundin

35 Physiotherapy in the management of hemophilia 247
Sébastien Lobet and David Stephensen

36 Outcome assessment in hemophilia 253
Pradeep M. Poonnoose and Alok Srivastava

Part XI: Transfusion-transmitted Disease

37 Viral hepatitis and hemophilia 265
Michael Makris and Geoffrey Dusheiko

38 Transfusion-transmitted disease: emerging infections 272
Thomas R. Kreil

39 vCJD and hemophilia 277
Carolyn M. Millar

Part XII: Gene Therapy

40 Hemophilia gene therapy: an overview 285
David Lillicrap

41 Gene therapy trials in hemophilia A and B 291
Katherine A. High

42 Gene therapy: molecular engineering of factor VIII and factor IX 298
Sundar R. Selvaraj and Steven W. Pipe

Part XIII: Laboratory

43 Laboratory and quality control of assays 311
Steve Kitchen

44 Standardization of assays in hemophilia 318
Sanj Raut and Trevor W. Barrowcliffe

45 Global laboratory assays in hemophilia 328
Benny Sørensen and Guy Young

Part XIV: Women and Bleeding Disorders

46 Obstetrics and gynecology: hemophilia 337
Rezan A. Kadir and Christine A. Lee

47 Women and von Willebrand disease 345
Peter A. Kouides

Part XV: von Willebrand Disease

48 von Willebrand disease: molecular aspects 355
Daniel Hampshire and Anne Goodeve

49 von Willebrand disease: epidemiology 362
Francesco Rodeghiero and Giancarlo Castaman

50 von Willebrand disease: biological diagnosis 370
Veronica H. Flood and Robert R. Montgomery

51 Classification and clinical aspects of von Willebrand disease 377
Augusto B. Federici

52 Treatment of von Willebrand disease: desmopressin 386
Pier M. Mannucci

53 Treatment of von Willebrand disease: therapeutic concentrates 390
Erik E. Berntorp

Part XVI: Rare Bleeding Disorders

54 Factor II 399
Jan Astermark

55 Factor V and combined factor V and VIII deficiencies 403
Flora Peyvandi and Marzia Menegatti

56 Congenital factor VII deficiency 413
Angelika Batorova

57 Factor X and factor X deficiency 421
David J. Perry

58 Factor XI deficiency 428
Paula H.B. Bolton-Maggs and Uri Seligsohn

59 Factor XIII deficiency 436
Diane Nugent and Loan Hsieh

60 Fibrinogen deficiency 445
Michael Laffan

61 Miscellaneous rare bleeding disorders 452
Frederico Xavier and Amy D. Shapiro

Part XVII: Emergency Medicine

62 Emergency management of hemophilia 463
W. Keith Hoots

Part XVIII: Evaluation of Hemophilia

63 Clinical trials and other methodologies 473
Sharyne M. Donfield and Alice E. Lail

64 Quality of life in hemophilia 478
Sylvia von Mackensen and Alessandro Gringeri

65 The economics of hemophilia treatment 489
Katarina Steen Carlsson and Erik E. Berntorp

Part XIX: Comprehensive Care and Delivery of Care

66 Hemophilia databases 497
Charles R.M. Hay

67 Comprehensive care and delivery of care: the developed world 502
Christopher A. Ludlam and Cedric R.J.R. Hermans

68 Comprehensive care and delivery of care in hemophilia: the developing world 508
Alok Srivastava and Auro Viswabandya

69 Comprehensive care and delivery of care: the global perspective 515
Mark W. Skinner and Alison M. Street

Index 523

Color plate section can be found facing page 202