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