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Understanding the mechanism of platelet thrombus formation under blood flow conditions and the effect of new antiplatelet agents.

Abstract：

:Platelet aggregation induced by stirring of a platelet suspension after activation by the exogenous addition of stimulants, such as ADP, epinephrine and thrombin, has long been used as a platelet function test, and for the screening of antiplatelet agents. Since platelet aggregation has been demonstrated to be mediated exclusively by the binding of plasma fibrinogen to the activated GP IIb/IIIa, anti-GP IIb/IIIa agents, which can completely inhibit platelet aggregation, were expected to become among the most potent of antithrombotic agents. The strong preventive effects of anti-GP IIb/IIIa agents against thrombotic complications after coronary intervention, and the weaker preventive effects of the same agents against the onset of coronary thrombosis in unstable angina pectoris patients point to both the efficacy and the limitations of anti-GP IIb/IIIa antithrombotic agents. Recently, many investigators have reported that platelets play a major role in thrombus formation at sites exposed to blood flow. Several platelet-function assay systems have been developed to elucidate the mechanism of thrombus formation under blood flow conditions. Numerous studies have demonstrated that von Willebrand factor (VWF) and its interaction with its receptors on platelets, including GP Ibalpha and GP IIb/IIIa, play essential roles not only in platelet activation, but also in platelet adhesion and possibly platelet cohesion. These findings prompted us to explore whether the VWF-mediated process of thrombus formation could be exploited as a target for potential antiplatelet agents. Moreover, recent studies have demonstrated that multiple synergistic signals, including those mediated by catecholamine receptors, purine nucleotide receptors, as well as some types of collagen receptors are involved in the process of VWF-mediated platelet thrombus formation. We now have new antiplatelet agents on the horizon, targeted against thrombus formation under blood flow conditions.

journal_name

Curr Vasc Pharmacol

journal_title

Current vascular pharmacology

authors

Goto S

doi

10.2174/1570161043476456

keywords:

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

23-32

issue

eissn

1570-1611

issn

1875-6212

journal_volume

pub_type

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Understanding the mechanism of platelet thrombus formation under blood flow conditions and the effect of new antiplatelet agents.