Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Reviews
Basic Principles of Platelet Biology and Clinical Implications
Dominick J. AngiolilloMasafumi UenoShinya Goto
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2010 Volume 74 Issue 4 Pages 597-607

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Abstract

Platelet activation and subsequent accumulation at sites of vascular injury are the first steps in hemostasis. Excessive platelet activation after atherosclerotic plaque rupture or endothelial cell erosion may also lead to the formation of occlusive thrombi, which are responsible for acute ischemic events. Multiple pathways are involved in platelet activation, including those activated by adenosine diphosphate (ADP), thromboxane A2 (TXA2), serotonin, collagen, and thrombin. Antiplatelet agents used for prevention of atherothrombosis have focused on blocking the formation of TXA2 (eg, aspirin) and interfering with ADP stimulation mediated by the P2Y12 receptor (eg, clopidogrel). These agents, used alone or in combination, significantly decrease the risk for atherothrombotic events, but a significant residual risk for recurrent ischemic events remains. This has been, in part, attributed to persistence of elevated platelet reactivity despite the use of these agents. Several novel antiplatelet agents are currently under clinical development, with the goal of achieving more efficacious platelet inhibition. These include agents that more efficiently block TXA2-mediated effects, as well as more potent P2Y12 receptor antagonists. In addition, inhibition of the protease-activated receptor-1 platelet activation pathway stimulated by thrombin has emerged as a rational target for clinical development. An overview of the basic principles of platelet biology is given and currently available antiplatelet agents, as well as those under clinical development, are reviewed. (Circ J 2010; 74: 597-607)

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© 2010 THE JAPANESE CIRCULATION SOCIETY
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