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(Circulation Research. 2003;92:944.)
© 2003 American Heart Association, Inc.

Editorials

CD40-CD40L and Platelet Function

Beyond Hemostasis

Jane E. Freedman

From the Whitaker Cardiovascular Institute and Evans Department of Medicine, Boston University School of Medicine, Boston, Mass.

Correspondence to Jane E. Freedman, MD, Boston University School of Medicine, 715 Albany St, W507, Boston, MA 02118. E-mail freedmaj@bu.edu

Key Words: platelets • CD40/CD40L • thrombosis • inflammation

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Traditionally, platelets have been thought of as anuclear, subcellular fragments derived from megakaryocytes circulating in blood as small discs and mitigating hemorrhage. This hemostatic process requires platelet activation, a complex chain of events involving rapid structural changes that activate adhesion receptors, remodel the cytoskeleton, and lead to the eventual synthesis and secretion of various platelet-derived factors. The result of this cascade is the formation of platelet-dependent thrombosis that primarily attenuates bleeding but, in pathophysiological settings, contributes to occlusive vascular events. These clinical realities have led to the bias that platelets are primarily involved in thrombosis and hemostasis. This bias has been reflected in the predominant use of platelet aggregometry as the standard method for quantifying platelet activation ex vivo. This technique, however, only identifies platelet-platelet binding (homotypic aggregates) and, in clinical settings, has promoted a relatively simplistic vision of platelet function. The focus on platelet-dependent thrombosis has made the platelet aggregate a common therapeutic target in syndromes involving vascular occlusion. However, merely preventing the process of platelet-platelet binding may not always translate into clinical efficacy as seen in the recent disappointing results associated with the use of the oral IIb/IIIa inhibitors.¹

Recently, studies have suggested that platelets also participate in inflammatory reactions. Platelets are known to produce inflammatory mediators including platelet-derived growth factor, platelet factor 4, and transforming growth factor-ß. Platelets are also known to bind, via P-selectin (CD62P) expressed on the surface of activated platelets to the leukocyte receptor, P-selectin glycoprotein ligand-1 (PSGL-1). The relevance of this binding is . . . [Full Text of this Article]

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