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Platelets in Thrombotic and Non-thrombotic Disorders: Pathophysiology, Pharmacology, and Therapeutics FREE TO VIEW

Alex C. Spyropoulos
Chest. 2003;124(3):1182-1183. doi:10.1378/chest.124.3.1182
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By Paolo Gresele, Clive P. Page, Valentin Fuster, and Jos Vermylen, eds. Cambridge, UK: Cambridge University Press, 2002; 1124 pp; $300

That platelets—small, anuclear, discoid cells in the vascular system—have attracted so much interest among basic scientists, clinical researchers, and practicing physicians as to warrant full textbooks dedicated to them, represents a major milestone in vascular science. Platelets occupy a primary role in coronary artery disease, cerebrovascular disease, and peripheral vascular disease, which comprise the major causes of death and disability in the Western world. Medical science has witnessed exponential advances in the understanding of platelet physiology, molecular biology, and pharmacogenetics, a more thorough understanding of the role of the platelet in pathologic conditions involving hemostatic, atherothrombotic, and nonhemostatic disorders, and a greater appreciation of the clinical benefits and pharmacotherapy of antiplatelet agents. Despite these advances, there has been no comprehensive, timely, and authoritative reference book covering the subject in recent years. Platelets in Thrombotic and Non-thrombotic Disorders: Pathophysiology, Pharmacology, and Therapeutics fills this gap by providing a book that is both detailed and exhaustive yet easily consulted for the latest developments in platelet ultrastructure, function (including receptor signaling, activation, adhesion, aggregation, and amplification), pathophysiology, pharmacology, and therapeutics.

The book itself is multidisciplinary in scope, as the editors themselves hail from multiple specialties and have included contributions from 157 basic scientists, clinical researchers, and internationally renowned experts in the field, including some of the founding “fathers” of modern platelet biology. It is divided into five parts and 72 chapters (including 15 color plates), encompassing platelet physiology, methodology, pathology, pharmacology, and therapy. The first section, covering physiology, begins with a historical introduction by J. F. Mustard, a pioneer in platelet research. Following this are extensive discussions of the complex mechanisms of megakaryocytopoiesis, thrombopoietin regulation, the relatively new concept of platelet heterogeneity, platelet cytoskeletal structure, platelet receptors and signaling mechanisms, and detailed chapters on the entire scope of important physiologic platelet functions. These include adhesion and shape change, activation and release reactions, and aggregation and amplification loops. In the chapter on platelet procoagulant activities, H. C. Hemker details the recent appreciation of the central role of the platelet in a more cell-based model of thrombin generation. The remaining chapters include information on platelet chemotaxis, leukocyte interactions, and vascular control of platelet function.

Part II covers methodology, and includes discussions on in vitro assays (including newer techniques such as flow cytometry) in evaluating platelet function and activation, with an emphasis in monitoring inhibition of glycoprotein IIb/IIIa antagonists. Part III covers pathology, including subsections on hemostatic, thrombotic, and nonhemostatic disorders, and incorporates chapters on the classic thrombocytopenic disorders such as hereditary, immune-mediated, and drug-induced thrombocytopenias. A discussion of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome includes new insights into pathogenesis via deficiencies of von Willebrand factor-cleaving protease. Disorders of platelet function, including adhesive protein receptors, platelet secretion, and signal transduction are included in separate chapters. The thrombosis subsection includes all the recent and remarkable advances in the understanding of the role of platelet activation in the pathophysiology of coronary atherosclerosis-thrombosis. There is an interesting and somewhat controversial chapter by A. D. Blann and G. Y. H. Lip on the role of platelets in venous thromboembolism. The subsection concludes with gene regulation of platelet function, including discussions on glycoprotein complex polymorphisms. The final subsection in this part includes both conventional platelet interactions in such disease processes as disseminated intravascular coagulation and bacterial, viral, parasitic, renal, and tumor functions, as well as more unconventional and controversial areas of platelet involvement such as allergic and inflammatory diseases, embryonic development, psychiatric and neurologic disorders, and inflammatory bowel disease.

Part IV comprises separate chapters on platelet pharmacology including aspirin, the thienopyridines, and glycoprotein IIb/IIIa antagonists, in addition to more novel approaches such as pharmacogenetics, cardiovascular gene therapy, and pharmacomodulatory anti-inflammatory platelet therapy. The book concludes with a section on antiplatelet therapy and evidence-based treatment strategies in cardiology, neurology, and peripheral vascular disease, including a nice discussion by S. R. Mehta and others as to antiplatelet trial designs. An autobiographical afterword by G. V. R. Born, another founding father of modern platelet research, finishes this monumental work.

The shortcomings of this book are relatively minor. It would have been worthwhile to add conclusion sections and closing remarks to every chapter. There are some mistakes within chapters in cross-referencing other sections or chapters within the book (pages 179, 713–715). As this is meant to be a definitive and comprehensive book on platelet involvement in thrombotic disorders, it would have been helpful to include rare disorders or “zebras” of platelet pathology such as the sticky platelet syndrome, characterized by arterial and venous thrombosis due to hyperaggregability of platelets in platelet-rich plasma with adenosine diphosphate and/or epinephrine, as well as an expanded section on the platelet’s role in the antiphospholipid antibody syndrome. In the latter disorder, emerging insights point to platelet-derived procoagulant microparticles as key players in pregnancy loss. In addition, the chapter on other antiplatelet agents should have included pentoxifylline, as this agent is sometimes used in retinal artery thrombosis associated with antiphospholipid antibody syndrome or peripheral vascular disease (although this agent appears in the index, I could not find a discussion of its use). Lastly, the chapters on antiplatelet treatment in cardiology and neurology should have been expanded to include the (albeit small) role of antiplatelet therapy in patients with native or mechanical heart valve disease and the role of antiplatelet agents in atrial fibrillation (eg, a discussion of the Stroke Prevention in Atrial Fibrillation-1 and 3, Danish Atrial Fibrillation Aspirin Coagulation, and European Atrial Fibrillation trials).

These minor shortcomings do not detract from the reality that Platelets in Thrombotic and Non-thrombotic Disorders: Pathophysiology, Pharmacology, and Therapeutics represents a magnum opus on the subject, and will likely remain so as the editors plan to publish new editions every 3 to 4 years. It is a must-have for basic researchers, investigators, and clinicians interested in the study of platelets.




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