Von Willebrand Disease: Basic and Clinical Aspects

263 Pages·2011·6.043 MB·English

by  Augusto B. Federici, Christine A. Lee, Erik E. Berntorp, David Lillicrap, Robert R. Montgomery

Von Willebrand Disease
Von Willebrand Disease
Basic and Clinical Aspects
Edited by
Augusto B. Federici MD
Associate Professor of Hematology
Division of Hematology and Transfusion Medicine
L. Sacco University Hospital
Department of Internal Medicine
University of Milan
Milan, Italy
Christine A. Lee MA, MD, DSc (Med), FRCP, FRCPath,
FRCOGad eundem
Emeritus Professor of Haemophilia
University of London
London, UK
Erik E. Berntorp MD, PhD
Professor of Hemophilia
Malmö Centre for Thrombosis and Haemostasis
Lund University
Skåne University Hospital
Malmö, Sweden
David Lillicrap MD
Professor
Department of Pathology and Molecular Medicine
Richardson Laboratory
Queen’s University
Kingston, ON, Canada
Robert R. Montgomery MD
Professor of Pediatric Hematology
Department of Pediatrics
Medical College of Wisconsin;
Senior Investigator
Blood Research Institute
Blood Center of Wisconsin
Milwaukee, WI, USA
A John Wiley & Sons, Ltd., Publication
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Library of Congress Cataloging-in-Publication Data
Von Willebrand disease : basic and clinical aspects / edited by Augusto B. Federici ... [et al.].
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4051-9512-6 (hardcover : alk. paper)
1. Von Willebrand disease. I. Federici, Augusto B.
[DNLM:1. von Willebrand Diseases. WH 312]
RC647.V65V66 2011
616.1'57–dc22
2010036377
A catalogue record for this book is available from the British Library.
This book is published in the following electronic formats: ePDF 9781444329933;
Wiley Online Library 9781444329926; ePub 9781444329940
Set in 9/11.5 pt Sabon by Toppan Best-set Premedia Limited
01 2011
Contents
Contributors, vii
Foreword, xi
Preface, xiii
1 Historical perspective on von Willebrand disease, 1
Erik Berntorp and Margareta Blombäck
2 Biosynthesis and organization of von Willebrand factor, 7
Sandra L. Haberichter
3 von Willebrand factor structure and function, 30
Robert R. Montgomery and Sandra L. Haberichter
4 Modulation of von Willebrand factor by ADAMTS13, 49
Jennifer Barr and David Motto
5 Animal models in von Willebrand disease, 63
Cécile V. Denis, Olivier D. Christophe and Peter J. Lenting
6 Classifi cation of von Willebrand disease, 74
Javier Batlle, Almudena Pérez-Rodríguez and
María Fernanda López-Fernández
7 The epidemiology of von Willebrand disease, 86
Giancarlo Castaman and Francesco Rodeghiero
8 Clinical aspects of von Willebrand disease: bleeding history, 91
Paula D. James and Alberto Tosetto
9 Laboratory diagnosis of von Willebrand disease: the phenotype, 100
Ulrich Budde and Emmanuel J. Favaloro
10 Molecular diagnosis of von Willebrand disease: the genotype, 114
Anne C. Goodeve and Reinhard Schneppenheim
11 Clinical, laboratory, and molecular markers of type 1 von
Willebrand disease, 127
David Lillicrap, Francesco Rodeghiero, and Ian Peake
12 Clinical, laboratory, and molecular markers of type 2 von
Willebrand disease, 137
Dominique Meyer, Edith Fressinaud, and Claudine Mazurier
13 Clinical, laboratory, and molecular markers of type 3 von
Willebrand disease, 148
Luciano Baronciani, Augusto B. Federici, and Jeroen C.J. Eikenboom
14 Pediatric aspects of von Willebrand disease, 166
Jorge Di Paola and Thomas Abshire
v
CONTENTS
15 Women with von Willebrand disease, 174
Christine A. Lee, Rezan A. Kadir, and Peter A. Kouides
16 On the use of desmopressin in von Willebrand disease, 186
Stefan Lethagen, Augusto B. Federici, and Giancarlo Castaman
17 The use of plasma-derived concentrates, 200
Pier Mannuccio Mannucci and Massimo Franchini
18 Prophylaxis in von Willebrand disease, 207
Erik Berntorp
19 Pathophysiology, epidemiology, diagnosis, and treatment of acquired von
Willebrand syndrome, 214
Ulrich Budde, Augusto B. Federici and Jacob H. Rand
20 Gene therapy for von Willebrand disease, 231
Marinee K.L. Chuah, Inge Petrus, and Thierry VandenDriessche
Index, 245
vi
Contributors
Thomas C. Abshire MD Ulrich Budde MD
Senior Vice President Director
Medical Services and the Medical Science Institute; Department of Hemostaseology
Chief Medical Offi cer Medilys Laborgesellschaft mbH
BloodCenter of Wisconsin c/o Asklepios Klinik Altona
Milwaukee, WI, USA Hamburg, Germany
L uciano Baronciani PhD Giancarlo Castaman MD
Hospital Scientist Consultant Haematologist
Angelo Bianchi Bonomi Haemophilia and Department of Cell Therapy and Hematology
Thrombosis Centre Hemophilia and Thrombosis Center
Department of Medicine and Medical Specialities San Bortolo Hospital
IRCCS Maggiore Policlinico Hospital Vicenza, Italy
Mangiagalli and Regina Elena Foundation and
University of Milan Olivier D. Christophe PhD
Milan, Italy Senior Researcher
INSERM Unit 770
Jennifer Barr BS Le Kremlin- Bic ê tre, France
Department of Anatomy and Cell Biology
University of Iowa Carver College of Medicine M arinee K.L. Chuah PhD
Iowa City, IA, USA Professor
Flanders Institute for Biotechnology (VIB)
Javier Batlle MD Vesalius Research Center
Chairman Servicio de Hematologí a y Hemoterapia. University of Leuven
INIBIC. C. Hospitalario Universitario A Coruñ a; Leuven;
Associate Professor of Department of Medicine Faculty of Medicine and Pharmacy
School of Medicine University Hospital Campus Jette
University of Santiago de Compostela Free University of Brussels (VUB)
A Coru ñ a, Spain Brussels, Belgium
Margareta Blomb ä ck MD PhD Cecile V. Denis PhD
Professor Emeritus Director of Research
Department of Molecular Medicine and Surgery INSERM Unit 770
Division of Clinical Chemistry and Blood Le Kremlin- Bic ê tre, France
Coagulation Research
The Karolinska Institute
Karolinska University Hospital
Stockholm, Sweden
vii
CONTRIBUTORS
Jorge Di Paola MD S andra L. Haberichter PhD
Associate Professor of Pediatrics and Genetics Associate Professor
Postle Family Chair in Pediatric Cancer and Blood Department of Pediatrics – Hematology/Oncology
Disorders Medical College of Wisconsin
University of Colorado Denver School of Medicine Milwaukee, WI, USA
The Children’ s Hospital
Aurora, CO, USA Paula D. James MD, FRCPC
Associate Professor, Hematologist
Jeroen C.J. Eikenboom MD, PhD Queen ’ s University
Associate Professor Kingston, ON, Canada
Department of Thrombosis and Hemostasis
Leiden University Medical Center R ezan A. Kadir MD, FRCS (ed), MRCOG, MD
Leiden, the Netherlands Consultant Obstetrician and Gynaecologist
The Royal Free Hospital
Emmanuel J. Favaloro PhD London, UK
Senior Hospital Scientist
Department of Haematology P eter A. Kouides MD
Institute of Clinical Pathology and Medical Medical and Research Director
Research (ICPMR) Mary M Gooley Hemophilia Center
Westmead Hospital Rochester General Hospital
Westmead, NSW, Australia Rochester, NY, USA
Massimo Franchini MD Peter J. Lenting PhD
Head Director of Research
Immunohematology and Transfusion Center INSERM Unit 770
Department of Pathology and Laboratory Medicine Le Kremlin- Bic ê tre, France
University Hospital of Parma
Italy S tefan Lethagen MD, PhD
Director of Copenhagen Haemophilia Centre
Edith Fressinaud MD, PhD Thrombosis and Haemostasis Unit
Consultant Haematologist Department of Haematology
Centre National de Ré f é rence de la Maladie de Copenhagen University Hospital
Willebrand Copenhagen, Denmark;
Service d’ H é matologie biologique International Medical Director
H ô pital Antoine B é cl è re Director of Medical & Science Haemostasis
Clamart, France Department
Global Development
A nne Goodeve BSc, PhD Novo Nordisk
Reader and Head, Haemostasis Research Group S ø borg, Denmark
Department of Cardiovascular Science
Faculty of Medicine, Dentistry and Health Mar í a Fernanda Ló pez - Fern á ndez MD
University of Sheffi eld; Head, Hemostasis and Thrombosis
Principal Clinical Scientist Servicio de Hematologí a y Hemoterapia
Sheffi eld Diagnostic Genetics Service Complexo Hospitalario Universitario de A Coruñ a
Sheffi eld Children’ s NHS Foundation Trust A Coru ñ a, Spain
Sheffi eld, UK
viii
CONTRIBUTORS
P ier Mannuccio Mannucci MD Jacob H. Rand
Professor of Medicine Hematology Laboratory
Angelo Bianchi Bonomi Haemophilia and Department of Pathology
Thrombosis Centre Montefi ore Center
University of Milan and IRCCS Maggiore Hospital Bronx, NY, USA
Milan, Italy
F rancesco Rodeghiero MD
Claudine Mazurier PhD Director
Head of Analytical Department, Preclinical Department of Cell Therapy and Hematology
Development San Bortolo Hospital
Laboratoire Franç ais du Fractionnement et des Vicenza, Italy
Biotechnologies
Lille, France R einhard Schneppenheim MD, PhD
Director
D ominique Meyer MD Department of Pediatric Hematology and Oncology
Professor of Haematology University Medical Center Hamburg- Eppendorf
Centre National de Ré f é rence de la Maladie de Hamburg, Germany
Willebrand;
University Paris- Sud Alberto Tosetto MD
France Senior Consultant
Department of Hematology
D avid Motto MD, PhD San Bortolo Hospital
Assistant Professor Vicenza, Italy
Departments of Internal Medicine and Pediatrics
University of Iowa Carver College of Medicine Thierry VandenDriessche PhD
Iowa City, IA, USA Group Leader
Flanders Institute for Biotechnology (VIB);
I an Peake BSc, PhD Vesalius Research Center
Sir Edward Mellanby Professor of Molecular University of Leuven
Medicine Leuven;
Department of Cardiovascular Science Faculty of Medicine and Pharmacy
University of Sheffi eld Medical School University Hospital Campus Jette
Sheffi eld, UK Free University of Brussels (VUB)
Brussels, Belgium
A lmudena P é rez - Rodr í guez PhD
Post - doctoral Investigator
Servicio de Hematologí a y Hemoterapia— INIBIC
Complexo Hospitalario Universitario de A Coruñ a
A Coru ñ a, Spain
I nge Petrus PhD
Flanders Institute for Biotechnology (VIB)
Vesalius Research Center
University of Leuven
Leuven, Belgium
ix
Foreword
I feel very honored to have been asked to write the bleeding without success but, when treated with frac-
foreword to this book on von Willebrand disease tion I - 0, the bleeding stopped. It is possible that the
(VWD). I am now the oldest living scientist to have platelet treatment was the reason why she later devel-
experience in this area, and thus it may be of interest oped antibodies to VWD. At that time there were no
for readers to learn about some early experiences that oral contraceptives, which have revolutionized the
I shared with the late Dr. Inga- Marie Nilsson, which management of menorrhagia in patients with VWD.
I have described below. Since I started working with In this particular patient, we used testosterone and
VWD in the mid - 1950s, there has been enormous later hysterectomy (under prophylaxis of fraction I - 0)
progress in the management of the disease in terms to deal with the menstrual bleedings.
of knowledge about mechanisms, treatment, and To persuade doctors that a patient had to be treated
underlying genetics. We have been able to follow this with a concentrate was a diffi cult task. I remember
development in Stockholm because the hemophilia the case of a 13 - year - old boy who developed severe
center here is currently responsible for the treatment head trauma as a result of falling from a bicycle.
of 40 patients with type 3 VWD (i.e., the most severe Despite the fact that the boy had a bleeding chart
form). saying that he should be treated immediately in the
In the 1950s there were only a few known cases of event of a trauma and the fact that I informed the
the disease — which was mostly called “ pseudohemo- doctor that the usual signs do not develop in bleeders
philia ” — in addition to those cases known in the immediately but sometimes several days later, the
Å land Islands, where the disease was fi rst identifi ed doctor refused to treat the boy with concentrates and
by Erik von Willebrand. This was probably because he died from severe brain hemorrhage.
most patients with type 3 VWD died young, either in In 1958 we started prophylactic treatment in
utero or, if the patient was female and survived until patients with hemophilia to avoid joint destruction.
puberty, as a result of menstrual bleeding. I remember However, it was not until many years later that we
some touching letters written at the end of the 19th realized that patients with type 3 VWD also required
century from a businessman to his wife, who was prophylaxis; therefore, some of them developed joint
mostly bedridden owing to menstrual bleedings. This disabilities. We also did not know that the concen-
woman was an ancestor of a young woman from trates with which we treated our patients could
Stockholm with type 3 VWD, who is currently living contain hepatitis C virus, which has led to the prema-
a normal family life thanks to therapy in early child- ture death of some patients.
hood with the Swedish fraction I- 0 (which contained This book has become a very comprehensive and
von Willebrand factor [VWF], factor VIII [FVIII], and useful work into which many of the authors have put
fi brinogen) and later with commercial VWF- c ontaining great efforts to make their chapters not only informa-
concentrates. tive but also easy to understand. Progress, diffi culties,
When taking a bleeding history for a female in the and alternative ways to diagnose phenotypes and gen-
1950s, it was useful to ask whether she had been otypes are described. Molecular diagnosis of type 1,
scolded in school for dropping blood onto her handi- type 2 and its subgroups, and type 3 VWD are pre-
work after pricking her fi nger with a sewing needle. sented. In addition, a chapter on gene therapy looking
We learned that it was useful to analyze blood groups into the future is stimulating to read. Furthermore,
in family investigations, as we found that a healthy many authors have endeavored to include all relevant
child who showed no sign of having inherited the literature, which is very useful for students.
disease did not share the same father as the sick A problem with regard to historical aspects is that
sibling. We made several mistakes— one girl was the nomenclature has changed from FVIII - related
transfused with platelets during a severe menstrual antigen to VWF antigen. Therefore, some of the early
xi
FOREWORD
fi ndings with regard to the level of VWF in patients carriers of VWD only had a phenotypically mild
with blood group O or A have not been observed. bleeding disorder and often, but not always, the
Nevertheless, the topic of how to proceed in diagnosis common analyses of VWD indicated a mild disorder.
when the patient has blood group O or A has been However, we recorded the usefulness of an increased
thoroughly discussed. I have the impression that there ratio of FVIII/VWF:Ag for the diagnosis of what we
still are problems with regard to diagnosis of the called type 1 VWD in these families.
phenotypes, particularly with regard to the diagnosis It must have been an enormous task for the editors
of type 1 VWD, even if preanalytic problems are to encourage all the authors to write, although pos-
taken into account, for example the quality of meth- sibly some welcomed the opportunity to put together
odology and the importance of telling the patient to their experience in a comprehensive chapter. The
rest and not to run or be stressed, etc, before blood efforts on trying to collate experience in multicenter
sampling. I made a serious mistake once when analyz- studies on prophylaxis and diagnostic scores is very
ing changes in VWF during the menstrual cycle — the valuable and, of course, needs to be supported in
volunteers were not well informed about resting order to solve the many diffi culties that remain in the
before sampling and we therefore misinterpreted the diagnosis and management of VWD.
results; there are not such great variations in FVIII
and VWF during the menstrual cycle as initially Margareta Blombä ck
suggested. Professor Emeritus
When investigating families with type 3 VWD, we Karolinska Institutet
found that the parents and siblings who were genetic Sweden

xii