Table Of ContentPlatelets in Thrombotic and
Non-thrombotic Disorders
Platelets have attracted increasing interest among clinicians and
basic scientists over recent years, and are now known to play a part
in many physiological and pathological conditions. In fact,
platelets are involved in diseases responsible for the majority of
disability and death worldwide, including myocardial infarction,
stroke, peripheral vascular disease, cancer, and many infections.
Platelets are also studied as a model in many areas of neurobiology,
pharmacology, biochemistry and molecular biology.
This timely reference provides a comprehensive, detailed, up-
to-date resource for clinicians and researchers, covering the struc-
ture and function of platelets and their role in pharmacology,
pathogenesis and therapeutics. It is organized into sections cover-
ing platelet physiology, laboratory and methodological issues,
platelet involvement in disease, including hemostatic and non-
hemostatic conditions, platelet pharmacology, and treatment in
the clinic.
With contributions from leading authorities including some of
the founders of modern platelet studies, this is the definitive refer-
ence and guide to the diagnosis and therapeutics of diseases
involving platelets. Chapters are devised to provide a critical
review of the most clinically relevant aspects of the subject, with
extensive references and easy-to-read take-home messages. It will
be an essential resource for biomedical scientists and clinicians in
hematology, vascular medicine, cardiology, thrombosis and
related disciplines.
Paolo Greseleis Associate Professor of Internal Medicine, Section
of Internal and Cardiovascular Medicine, Department of Internal
Medicine, University of Perugia, Italy
Clive Pageis Professor of Pharmacology, Division of Pharmacology
and Therapeutics and Director of the Sackler Institute of
Pulmonary Pharmacology and Therapeutics, Guy’s, King’s and St
Thomas’ School of Biomedical Sciences, London
Valentin Fuster is Director of the Zena and Michael A. Wiener
Cardiovascular Institute and the Richard Gorlin, M.D./Heart
Research Foundation Professor of Cardiology at the Mount Sinai
Medical Center and School of Medicine, New York, New York
Jos Vermylen is Professor of Internal Medicine, Centre for
Molecular and Vascular Biology, University of Leuven, Belgium
Cambridge Books Online © Cambridge University Press, 2009
Cambridge Books Online © Cambridge University Press, 2009
Platelets
in Thrombotic and Non-thrombotic Disorders
Pathophysiology, Pharmacology and Therapeutics
Edited by
Paolo Gresele
Section of Internal and Cardiovascular Medicine
Department of Internal Medicine
University of Perugia, Italy
Clive P.Page
Sackler Institute of Pulmonary Pharmacology
King’s College London, UK
Valentin Fuster
The Mount Sinai Medical Center and
School of Medicine
New York, USA
and
Jos Vermylen
Centre for Molecular and Vascular Biology
University of Leuven, Belgium
Cambridge Books Online © Cambridge University Press, 2009
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Cambridge University Press
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© Cambridge University Press, 2002
This book is in copyright. Subject to statutory exception and to the provision of
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without the written permission of Cambridge University Press.
First published in print format 2002
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isbn-13 978-0-511-05720-5 eBook (Adobe Reader)
isbn-10
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isbn-13 978-0-521-80261-1 hardback
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isbn-10 0-521-80261-X hardback
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s for external or third-party internet websites referred to in this book, 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 which is in accord with accepted standards and practice at the time of
publication. Nevertheless, the authors, editors and publishers can make no warranties
that the information contained herein is totally free from error, not least because
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editors and publisher therefore disclaim all liability for direct or consequential
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advised to pay careful attention to information provided by the manufacturer of any
drugs or equipment that they plan to use.
Cambridge Books Online © Cambridge University Press, 2009
Contents
List of contributors ix
Editors’preface xxi
PART I PHYSIOLOGY
1 History of platelets 3
J. Fraser Mustard, Raelene L. Kinlough-Rathbone
and Marian A. Packham
2 Production of platelets 25
Arnaud Drouin and Elisabeth Cramer
3 Morphology and ultrastructure of platelets 41
James G. White
4 Platelet heterogeneity:physiology and
pathological consequences 70
Anthony Mathur and John F. Martin
5 Platelet membrane proteins as adhesion
receptors 80
Yoshiaki Tomiyama, Masamichi Shiraga and
Sanford J. Shattil
6 Dynamics of the platelet cytoskeleton 93
Kurt L. Barkalow, Hervé Falet and John Hartwig
7 Platelet organelles 104
Francine Rendu and Brigitte Brohard-Bohn
8 Platelet receptors for thrombin 113
Lawrence F. Brass, Marina Molino, Peter J.
O’Brien and Mark Kahn
9 Platelet receptors:ADP 127
Christian Gachet and Jean-Pierre Cazenave
10 Platelet receptors:prostanoids 140
Roberta Vezza and Garret A. FitzGerald
v
Cambridge Books Online © Cambridge University Press, 2009
vi Contents
11 Platelet receptors:collagen 158 28 Platelet–leukocyte interactions relevant to
Pia R-M. Siljander and Richard W. Farndale vascular damage and thrombosis 412
Chiara Cerletti, Virgilio Evangelista, Roberto
12 Platelet receptors:von Willebrand factor 179
Lorenzet and Giovanni de Gaetano
Jerry Ware and Zaverio M. Ruggeri
29 Vascular control of platelet function 432
13 Platelet receptors:fibrinogen 188
Scott Willoughby and Joseph Loscalzo
Edward F. Plow, Thomas A. Haas and
Tatiana V.Byzova
14 Platelet signalling:GTP-binding proteins 204 PART II METHODOLOGY
Jan-Willem N. Akkerman
30 In vitro assays for evaluating platelet function 459
15 Platelet phospholipases A 221
2 Perumal Thiagarajan and Kenneth K. Wu
Michael H. Gelb, Carine M. Mounier,
Ying Hefner and Steve P.Watson 31 Monitoring antiplatelet therapy 471
Dermot Cox and Desmond Fitzgerald
16 Roles of phospholipase C and phospholipase
D in receptor-mediated platelet activation 238 32 Flow cytometric analysis of platelet function 485
Mauro Torti and Eduardo G. Lapetina Alan D. Michelson, Marc R. Barnard, Lori A.
Krueger, A.L. Frelinger III and Mark I. Furman
17 Platelet signalling:calcium 260
Juan A. Rosado and Stewart O. Sage 33 Animal models of platelet-dependent
thrombosis 499
18 Platelet signalling:protein kinase C 272
Paolo Golino and Francesco Loffredo
Charles S. Abrams and Marcelo G. Kazanietz
19 Platelet signalling:tyrosine kinases 281
Sylviane Levy-Toledano PART III PATHOLOGY
20 Platelet signalling:cAMP and cGMP 290
A Hemostasis
James L. Daniel, Barrie Ashby and Fabio M.
Pulcinelli 34 Hereditary thrombocytopenias 515
Chris Van Geet, Kathleen Freson, Rita Devos
21 Platelet adhesion 304
and Jos Vermylen
Philip G. de Groot and Jan J. Sixma
35 Thrombocytopenias due to bone marrow
22 The platelet shape change 319
disorders 528
Adrian R.L. Gear and Renata K. Polanowsa-
Beng H. Chong and Colin Chesterman
Grabowska
36 Immune-mediated thrombocytopenia 542
23 Aggregation 338
Kathryn E. Webert and John G. Kelton
Marian A. Packham, Margaret L. Rand and
Raelene L. Kinlough-Rathbone 37 Thrombocytopenia in childhood 556
Cécile Kaplan, M. Dreyfus, V. Proulle and
24 Amplification loops:release reaction 357
G.Tchernia
Marc F. Hoylaerts
38 Alloimmune thrombocytopenia 569
25 Amplification loops:thromboxane generation 369
E. Anders Kolb and James B. Bussel
Paola Patrignani and Maria G. Sciulli
39 Drug-induced and drug-dependent immune
26 Platelet procoagulant activities:the
thrombocytopenias 584
amplification loops between platelets and
Andreas Greinacher, Petra Eichler and
the plasmatic clotting system 381
NorbetLubenow
H. Coenraad Hemker
40 Thrombotic thrombocytopenic purpura and
27 Platelets and chemotaxis 393
hemolytic uremic syndrome 610
Stefania Momi and Paolo Gresele
Miha Furlan
Cambridge Books Online © Cambridge University Press, 2009
Contents vii
41 Thrombocytosis and thrombocythemia 623 57 Platelet interactions with other cells related
Tiziano Barbui and Guido Finazzi to inflammatory diseases 869
Patrice E. Poubelle and Pierre Borgeat
42 Platelet adhesive protein defect disorders 639
Kenneth J. Clemetson and Jeannine M. 58 Platelets and the preimplantation stage of
Clemetson embryo development 885
Christopher O’Neill
43 Congenital disorders of platelet secretion 655
Marco Cattaneo 59 Platelets in psychiatric and neurological
disorders 894
44 Congenital platelet signal transduction
B. E. Leonard
defects 674
A. Koneti Rao 60 Platelets in inflammatory bowel disease 907
Elizabeth Carty, David S. Rampton and
45 Acquired platelet function defects 689
Carole E. Collins
Joel S. Bennett
46 Platelet storage and transfusion 707
Scott Murphy PART IV PHARMACOLOGY
B Thrombosis
61 Aspirin 919
47 Pathophysiology of arterial thrombosis 727 Carlo Patrono
Lina Badimon, Juan-Jose Badimon and
62 Pharmacology of ticlopidine and clopidogrel 929
ValentinFuster
Jean-Pierre Cazenave and Christian Gachet
48 Platelets and atherosclerosis 738
63 Platelet membrane glycoprotein (GP) IIb–IIIa
Peter Verhamme and Paul Holvoet
antagonists and acute arterial thrombosis 940
49 Platelet involvement in venous thrombosis David R. Phillips and Lisa Nannizzi-Alaimo
and pulmonary embolism 753
64 Other antiplatelet agents 955
Andrew D. Blann and Gregory Y. H. Lip
Luigi Iuliano, Fausta Micheletta and
50 Gene regulation of platelet function 760 Francesco Violi
Thomas J. Kunicki
65 Pharmacogenetics as a new antiplatelet
C Non-hemostatic disorders strategy 964
Giovanni de Gaetano, Chiara Cerletti and
51 Platelets and bacterial infections 783
LiciaIacoviello
Mark C. Herzberg and Ke Gong
66 Cardiovascular gene therapy:implications
52 Interactions of viruses and platelets and the
for platelet vessel wall interactions 978
inactivation of viruses in platelet concentrates
Pierre Zoldhelyi, Harold Eichstaedt, Thomas
prepared for transfusion 807
Jax, Janice M. McNatt, Zhi Qiang Chen,
Laurence Corash
Harnath S. Shelat, Harris Rose and James T.
53 Platelets and parasites 815 Willerson
Michel Joseph
67 Pharmacological modulation of the
54 Platelets and tumours 824 inflammatory actions of platelets 991
Maria Benedetta Donati and Virgilio Carla Cicala and Giuseppe Cirino
Evangelista
55 Platelets and renal diseases 837
PART V THERAPY
Paola Boccardo, Miriam Galbusera and
Giuseppe Remuzzi
68 Design of trials to evaluate antiplatelet agents 1003
56 Platelets and allergic diseases 852 Shamir R. Mehta, John W. Eikelboom and Salim
Simon Pitchford and Clive P. Page Yusuf
Cambridge Books Online © Cambridge University Press, 2009
viii Contents
69 Antiplatelet therapy in cardiology 1013
Herbert D. Aronow and Eric J. Topol
70 Antiplatelet therapies in neurology 1040
Graeme J. Hankey
71 Antiplatelet treatment in peripheral vascular
disease 1055
Raymond Verhaeghe
Afterword 1063
Platelets:a personal story
Gustav V.R. Born
Index 1073
Colour plates between pages 170 and 171
Cambridge Books Online © Cambridge University Press, 2009
Contributors
Charles S.Abrams
University of Pennsylvania
Basic Research Building II/III Room 912
421 Curie Blvd.
Philadelphia
PA 19104, USA
Jan-Willem N.Akkerman
Laboratory for Thrombosis and Haemostasis
Department of Haematology
University Medical Center Utrecht
Heldelberglaan 100
3584 CX Utrecht
The Netherlands
Herbert D.Aronow
Department of Cardiovascular Medicine
The Cleveland Clinic Foundation – Clinic Centre
9500 Euclid Avenue
Cleveland
Ohio, USA
Barrie Ashby
Department of Pharmacology and Sol Sherry Thrombosis
Research Center
Temple University Medical School Philadelphia
PA 19140, USA
Juan-Jose Badimon
Cardiovascular Institute
Mount Sinai School of Medicine
New York, USA
ix
Cambridge Books Online © Cambridge University Press, 2009
x List of contributors
Lina Badimon Gustav V.R.Born
Cardiovascular Unit The William Harvey Research Institute
CID/CSIC St. Bartholomew’s and the Royal London School of
Jordi Girona, 18–26 Medicine and Dentistry
08034 Barcelona, Spain University of London
Charterhouse Square
Tiziano Barbui London EC1M 6BQ, UK
Division of Hematology
Ospedali Riuniti Lawrence F.Brass
Largo Barozzi 1 Departments of Medicine and Pharmacology
24128 Bergamo, Italy Center for Experimental Therapeutics
913 BRB II/III
Kurt L.Barkalow 421 Curie Blvd
Brigham & Women’s Hospital Philadelphia
Hematology Division PA 19104–6069, USA
LMRC Building, Rm 301
221 Longwood Avenue Brigitte Brohard-Bohn
Boston U428 INSERM
MA 02115, USA Faculté de Pharmacie
4 avenue de l’Observatoire
Marc R.Barnard 75006 Paris, France
Center for Platelet Function Studies
University of Massachusetts Medical School James B.Bussel
55 Lake Avenue North Cornell University Medical Center
Worcester New York Hospital, USA
MA 01655, USA
Tatiana V.Byzova
Joel S.Bennett Joseph J. Jacobs Center for Thrombosis and Vascular
University Pennsylvania School of Medicine Biology
Room 914, BRB II/II Department of Molecular Cardiology
421 Curie Blvd. Cleveland Clinic Foundation
Philadelphia 9500 Euclid Avenue
PA 19014, USA Cleveland
OH 44195, USA
Andrew D.Blann
Haemostasis,Thrombosis and Vascular Biology Unit Elizabeth Carty
University Department of Medicine Department of Adult and Paediatric Gastroenterology
City Hospital St. Bartholomew’s and The Royal London School of
Birmingham B18 7QH, UK Medicine and Dentistry
London E1 2AD, UK
Paola Boccardo
Mario Negri Institute for Pharmacological Research Marco Cattaneo
Via Gavazzeni 11 Hemophilia and Thrombosis Centre
24125 Bergamo, Italy Department of Internal Medicine
University of Milano
Pierre Borgeat Via Pace 9
CRRI 20122 Milano, Italy
Centre de Recherche du CHUQ and Faculté de Médecine
Université Laval
2705 Boulevard Laurier
Ste-Foy
Qc G1V 4G2, Canada
Cambridge Books Online © Cambridge University Press, 2009
