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A Clinical Handbook
Edited by

Paolo Gresele
University of Perugia, Italy

Valentin Fuster
Mount Sinai School of Medicine, USA

Jos´ A. L´ pez
e o
Puget Sound Blood Center and University of Washington, USA

Clive P Page
King™s College London, UK

Jos Vermylen
University of Leuven, Belgium
Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo

Cambridge University Press
The Edinburgh Building, Cambridge CB2 8RU, UK
Published in the United States of America by Cambridge University Press, New York
Information on this title: www.cambridge.org/9780521881159

© Cambridge University Press 2008

This publication is in copyright. Subject to statutory exception and to the provision of
relevant collective licensing agreements, no reproduction of any part may take place
without the written permission of Cambridge University Press.
First published in print format 2007

ISBN-13 978-0-511-37913-0 eBook (NetLibrary)

ISBN-13 978-0-521-88115-9 hardback

Cambridge University Press has no responsibility for the persistence or accuracy of urls
for external or third-party internet websites referred to in this publication, and does not
guarantee that any content on such websites is, or will remain, accurate or appropriate.

Every effort has been made in preparing this book to provide accurate and up-to-date
information that is in accord with accepted standards and practice at the time of
publication. Nevertheless, the authors, editors and publisher can make no warranties that
the information contained herein is totally free fromerror, not least because clinical
standards are constantly changing through research and regulation. The authors, editors
and publisher therefore disclaimall liability for direct or consequential damages resulting
from the use of material contained in this book. Readers are strongly advised to pay careful
attention to information provided by the manufacturer of any drugs or equipment that
they plan to use.

List of contributors page v
Preface ix
Glossary xi

1 The structure and production of blood 12 Congenital disorders of platelet
platelets 1 function 201
Joseph E. Italiano, Jr. Marco Cattaneo

2 Platelet immunology: structure, functions, 13 Acquired disorders of platelet function 225
and polymorphisms of membrane Michael H. Kroll and Amy A. Hassan
glycoproteins 21
14 Platelet transfusion therapy 242
Yasuo Ikeda, Yumiko Matsubara, and Tetsuji Kamata
Sherrill J. Slichter and Ronald G. Strauss
3 Mechanisms of platelet activation 37
15 Clinical approach to the patient with
Lawrence Brass and Timothy J. Stalker
thrombosis 261
4 Platelet priming 53 Brian G. Choi and Valentin Fuster
Paolo Gresele, Emanuela Falcinelli, and Stefania Momi
16 Pathophysiology of arterial thrombosis 279
5 Platelets and coagulation 79 Juan Jose Badimon, Borja Ibanez, and Gemma Vilahur
Jose A. Lopez and Ian del Conde
´ ´
17 Platelets and atherosclerosis 293
6 Vessel wall-derived substances affecting Stephan Lindemann and Meinrad Gawaz
platelets 92
18 Platelets in other thrombotic conditions 308
Azad Raiesdana and Joseph Loscalzo
David L. Green, Peter W. Marks, and Simon Karpatkin
7 Platelet“leukocyte“endothelium
19 Platelets in respiratory disorders and
cross talk 106
in¬‚ammatory conditions 323
Kevin J. Croce, Masashi Sakuma, and Daniel I. Simon
Paolo Gresele, Stefania Momi, Simon C. Pitchford,
and Clive P. Page
8 Laboratory investigation of platelets 124
Eduard Shantsila, Timothy Watson,
20 Platelet pharmacology 341
and Gregory Y.H. Lip
Dermot Cox
9 Clinical approach to the bleeding patient 147
21 Antiplatelet therapy versus other
Jos Vermylen and Kathelijne Peerlinck
antithrombotic strategies 367
10 Thrombocytopenia 155 Nicolai Mejevoi, Catalin Boiangiu, and Marc Cohen
James B. Bussel and Andrea Primiani
22 Laboratory monitoring of antiplatelet
therapy 386
11 Reactive and clonal thrombocytosis 186
Paul Harrison and David Keeling
Ayalew Tefferi


23 Antiplatelet therapies in cardiology 407 26 Antiplatelet treatment of venous
thromboembolism 471
Pierluigi Tricoci and Robert A. Harrington
Menno V. Huisman, Jaapjan D. Snoep,
24 Antithrombotic therapy in Jouke T. Tamsma, and Marcel M.C. Hovens
cerebrovascular disease 437
James Castle and Gregory W. Albers
Index 483
25 Antiplatelet treatment in peripheral
arterial disease 458
Raymond Verhaeghe and Peter Verhamme


Marco Cattaneo, MD
Gregory W. Albers, MD
Unit` di Ematologia e Trombosi
Department of Neurology and
Ospedale San Paolo
Neurological Sciences
Dipartimento di Medicina,
Stanford Stroke Center
Chirurgia e Odontoiatria
Stanford University Medical Center
Universit` di Milano
Stanford, CA, USA
Milano, Italy
Juan Jose Badimon, PhD, FACC, FAHA
Cardiovascular Institute
Brian G. Choi, MD, MBA
Mount Sinai School of Medicine
Zena and Michael A. Wiener
New York, NY, USA
Cardiovascular Institute
Mount Sinai School of Medicine
Catalin Boiangiu, MD New York, NY, USA
Division of Cardiology
Newark Beth Israel Medical Center
Newark, NJ, USA Marc Cohen, MD, FACC
Division of Cardiology
Newark Beth Israel Medical Center,
Lawrence Brass, MD, PhD
and Mount Sinai School of Medicine
University of Pennsylvania
New York, NY, USA
Philadelphia, PA, USA

James Bussel, MD
Dermot Cox, BSc, PhD
Department of Pediatrics, and
Molecular and Cellular Therapeutics
Department of Obstetrics and Gynecology
Royal College of Surgeons in Ireland
Weill Medical College of Cornell
Dublin, Ireland
New York, NY, USA
Kevin J. Croce, MD, PhD
James Castle, MD Department of Medicine
Department of Neurology and Cardiovascular Division
Neurological Sciences Brigham and Women™s Hospital
Stanford University Medical Center Harvard Medical School
Stanford, CA, USA Boston, MA, USA


Amy A. Hassan, MD
Ian del Conde, MD
MD Anderson Cancer Center
Department of Internal Medicine
University of Texas
Brigham and Women™s Hospital
Houston, TX, USA
Boston, MA, USA

Marcel M. C. Hovens, MD
Emanuela Falcinelli, PhD
Section of Vascular Medicine
Division of Internal and
Department of General Internal
Cardiovascular Medicine
Department of Internal Medicine
Leiden University Medical Centre
University of Perugia
Leiden, The Netherlands
Perugia, Italy

Menno V. Huisman, MD, PhD
Valentin Fuster, MD, PhD
Section of Vascular Medicine
Zena and Michael A. Wiener
Department of General Internal
Cardiovascular Institute
Mount Sinai School of Medicine
Leiden University Medical Centre
New York, NY, USA
Leiden, The Netherlands
Meinrad Gawaz, MD
Borja Ibanez, MD
Cardiology and Cardiovascular Diseases
Cardiovascular Institute
Medizinische Klinik III
Mount Sinai School of Medicine

Eberhard Karls-Universit¨ t Tubingen
New York, NY, USA
Tubingen, Germany

Yasuo Ikeda, MD
David L. Green, MD, PhD
Department of Hematology
Department of Medicine (Hematology)
Keio University School of Medicine
New York University School of Medicine
Tokyo, Japan
New York, NY, USA

Joseph E. Italiano, Jr, MD
Paolo Gresele, MD, PhD
Hematology Division
Division of Internal and
Brigham and Women™s Hospital, and
Cardiovascular Medicine
Vascular Biology Program
Department of Internal Medicine
Children™s Hospital Boston, and
University of Perugia
Harvard Medical School
Perugia, Italy
Boston, MA, USA
Robert A. Harrington, MD
Tetsuji Kamata, MD
Duke Clinical Research Institute
Department of Anatomy
Duke University Medical Center
Keio University School of Medicine
Durham, NC, USA
Tokyo, Japan
Paul Harrison, PhD, MRCPath
Simon Karpatkin, MD
Oxford Haemophilia and
Department of Medicine (Hematology)
Thrombosis Centre
New York University School of Medicine
Churchill Hospital
New York, NY, USA
Oxford, UK


David Keeling, BSc, MD, FRCP, FRCPath Stefania Momi, PhD
Oxford Haemophilia and Thrombosis Centre Division of Internal and
Churchill Hospital Cardiovascular Medicine
Oxford, UK Department of Internal Medicine
University of Perugia
Michael H. Kroll, MD Perugia, Italy
Michael E DeBakey VA Medical Center,
Clive P. Page, PhD
and Baylor College of Medicine
Sackler Institute of Pulmonary
Houston, TX, USA
Division of Pharmaceutical Sciences
Stephan Lindemann, MD
King™s College London
Cardiology and Cardiovascular Diseases
London, UK
Medizinische Klinik III
Kathelijne Peerlinck, MD, PhD

Eberhard Karls-Universit¨ t Tubingen
Center for Molecular and Vascular Biology,
Tubingen, Germany
and Division of Bleeding and Vascular
Gregory Y.H. Lip, MD, FRCP
University of Leuven
Haemostasis Thrombosis and
Leuven, Belgium
Vascular Biology Unit
University Department of Medicine Simon C. Pitchford, PhD
City Hospital Leukocyte Biology Section
Birmingham, UK National Heart and Lung Institute
Imperial College London
Jose A. Lopez, MD
´ ´ London, UK
Puget Sound Blood Center, and
Andrea Primiani
University of Washington
Division of Hematology
Seattle, WA, USA

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