Platelet Function: Assessment, Diagnosis, and Treatment
Martin Quinn, Desmond Fitzgerald, eds
397 pages. Totowa, NJ: Humana Press; 2005. $125.00. ISBN 1-58829-244-4
The delicate balance of prothrombotic and antithrombotic processes responsible for clot formation is critical in the prevention of hemorrhage after injury and the maintenance of a patent vessel after plaque rupture. Platelets are anucleate cell-like particles pivotal in the prevention of hemorrhage and central in the formation of clot resulting from arterial disruption. Platelets are often viewed as simple structures; however, there is a growing appreciation of the importance of complex platelet signaling, intercellular interactions, and their modulation of nonthrombotic processes in the vasculature. In this context, the editors of Platelet Function: Assessment, Diagnosis, and Treatment assemble a group of experts in the field of platelet function and biology to examine relevant receptors and signaling pathways and to discuss their impact on platelet function.
Early characterization of platelet function involved examination of arachidonic acid metabolism, furthering an understanding of the therapeutic utility of cyclooxygenase inhibitors in vascular disease, most notably aspirin. The discovery and characterization of platelet receptors such as the adenosine diphosphate receptor and glycoprotein IIb/IIIa have been associated with the development of novel classes of antiplatelet drugs such as thienopyridine derivatives and glycoprotein IIb/IIIa receptor antagonists, respectively. However, further knowledge of receptor pathways and their inhibitors, as well as developing concepts in the interaction of platelets and inflammatory cells, has continued to advance our understanding of thrombosis. In Platelet Function, the editors briefly revisit some of these original topics while focusing on emerging areas of interest in thrombosis. The authors’ observations are often presented in the context of relevant established pharmacology. With both recent pharmacological success and failures in mind, the authors discuss both the mysteries of platelet function beyond merely the formation of homotypic aggregates and the limitations of available measurements of platelet function.
The book is divided into 3 sections containing a total of 16 chapters. The chapters are uniformly concise and informative. Each gives relatively brief overviews, making this book particularly appealing for the general reader with an interest in thrombosis. The fist and largest section of the book examines platelet physiology. Overall, this section is a clear, concise review of the basics of platelet activation and signaling. In the first overview chapter, the authors highlight both inside-out and outside-in signaling and introduce this concept to readers unfamiliar with the differences in platelet signaling. The chapters are enhanced with particularly clear figures that complement the text. The chapter on integrin signaling puts these pathways into perspective through discussions of the relevance of pharmacological therapies and the potential for the blockade of alternative receptors. Of note is the chapter (4) discussing the structure and function of the platelet cytoskeleton. In this chapter, the author outlines the protein complexes responsible for the organization of the platelet actin cytoskeleton. Platelet protein synthesis is another topic that is both novel and rapidly progressing, and the concepts are clearly presented. The relevance of this newly emerging field is discussed and includes practical advice for platelet biologists.
The second section, Assessing Platelet Function, discusses testing modalities, biomarkers, and the effect of specific forms of platelet blockade. The chapter (10) on glycoprotein IIb/IIIa receptor inhibition appropriately raises the question as to whether this target is the optimal approach and suggests that manipulation of the growing areas of platelet research may lead to the addition of alternative platelet targets. Although the reviews are thorough and clearly presented with only a minimal amount of repetition between chapters, they could have discussed in more detail the limitations of the currently available methods of measurement of platelet function. Drs Michelson and Furman clearly discuss the basic foundation and growing number of clinical settings in which markers of platelet activation are being used.
The third section of this book, Clinical Application, reviews antiplatelet agents and the assessment of platelet function in clinical trials. The highlight of this portion is the review of the platelet function testing used in various trials. This segues into Dr Kleiman’s chapter on platelet function testing in the clinical setting. The limitations of platelet measurements in clinical trials are clearly pointed out, although this well-summarized section could have been expanded. The issue of treatment failure and the use of the term “resistance” (the word commonly used for antithrombotic treatment failure in the context of platelet inhibitors) would have been a welcome addition. Because many of the current platelet function studies are being conducted in the context of aspirin or clopidogrel resistance, the relevance of the various methods of platelet function testing in these studies could have been presented in a simple manner.
Advances in the understanding of the mechanisms of thrombosis and the development of new techniques for studying its regulation have led to a clearer vision of thrombotic disease and the availability of new classes of antithrombotic drugs. This is an outstanding book for those who want a concise review of platelet function and its relevance to thrombotic disorders and current pharmacology. What is distinct about this book is that it goes beyond the standard discussion of platelet function and signaling pathways by adding clinical relevance and the potential for pharmacological manipulation and drug development. This book is a readable review, but its strength is the leaning toward newer areas and novel developments in platelet function. A greater discussion of new platelet technologies and imaging would have been welcome, but this book clearly presents emerging areas in platelet physiology, including platelet proteomics and gene expression. In summery, Platelet Function is a very useful book for anyone interested in the fundamentals of platelet function, platelet biomarkers, techniques for activation measurement, and thrombotic disorders.
Dr Freedman has received research grants from the American Heart Association, the National Heart, Lung, and Blood Institute, and Boehringer-Ingelheim.