Book Review

Platelets, Thrombosis, and the Vessel Wall

N Engl J Med 2001; 344:1560May 17, 2001

Article

Platelets, Thrombosis, and the Vessel Wall
(Advances in Vascular Biology. Vol. 6.) Edited by Michael C. Berndt. 339 pp., illustrated. Amsterdam, Harwood Academic, 2000. $90. ISBN: 90-5702-369-5

This book discusses key aspects of platelet function in the regulation of hemostasis and thrombosis. It covers topics ranging from the platelet cytoskeleton to the antiphospholipid-antibody syndrome. Among the many highlights of the book is the section on von Willebrand's disease, a group of quantitative and qualitative abnormalities of von Willebrand factor. These abnormalities are the most common causes of inherited bleeding disorders, with a prevalence of up to 1 percent of the population. The defect in primary hemostasis results from a failure of platelet adhesion at the site of vascular damage. New ways of classifying von Willebrand's disease according to its pathophysiologic characteristics are discussed by Sadler. López and colleagues review the glycoprotein Ib/IX/V complex, a group of proteins on the platelet surface that make it possible for the platelet to bind to matrix-bound von Willebrand factor. The authors point out that the Ib/IX/V complex forms a receptor with unique functions — platelet adhesion and activation — and they discuss how the binding of von Willebrand factor to the complex initiates platelet activation.

Du lucidly describes the dialogue between extracellular and intracellular compartments of the platelet. Some signaling pathways in the platelet are initiated with the binding of an agonist to a platelet membrane receptor; this causes the receptor to increase its affinity and thereby acquire the ability to respond to ligands such as fibrinogen and von Willebrand factor. Other signaling pathways are initiated after the ligation and clustering of integrins (transmembrane proteins that allow the attachment of cells to the extracellular matrix). The binding of ligands to receptors for platelet-derived growth factor or the thrombin receptor results in platelet spreading, secretion from intracellular granules, the availability of platelet membrane phospholipoprotein for coagulation, and clot retraction. Fox and Meyer, in discussing the platelet cytoskeleton, emphasize the similarity of cytoskeletal reorganizations in platelets to those in other cells, and Campbell and associates describe the background and current status of phosphoinositide-derived second-messenger molecules in platelet activation.

The important platelet membrane glycoprotein CD36 is discussed by Thorne and colleagues. Discrete functions of CD36 have been elucidated in lipid metabolism, fatty-acid transport, cell adhesion, angiogenesis, inflammation, and activation of transforming growth factor β. A deficiency of CD36 has been associated with hereditary hypertrophic cardiomyopathy.

The superb discussion of P-selectin by McEver surveys its structure, function, and interactions with P-selectin glycoprotein ligand 1. Andrews and Berndt review platelet–endothelial-cell adhesion molecule 1, which is required for the transendothelial migration of leukocytes. This protein maintains the integrity of the vascular endothelial-cell monolayer at junctions and also regulates cytoskeletal rearrangements that influence the shape and motility of cells. Thrombospondins are also reviewed, with an emphasis on their role in vascular development, atherogenesis, and thrombosis. The final section of the book addresses the diagnosis and treatment of resistance to activated protein C — a form of inherited thrombophilia. In some countries, up to 60 percent of patients with venous thromboembolism have resistance to activated protein C.

This book is part of a series that brings together important advances in all areas of vascular biology, a rapidly progressing field of study. Unfortunately, very few of the references are more recent than 1998, although each chapter is historically and scientifically well documented. I highly recommend this book to anyone interested in hemostasis, thrombosis, and vascular diseases.

Aaron J. Marcus, M.D.
Veterans Affairs New York Harbor Health Care System, New York, NY 10010