Objective-Tissue factor (TF) is the main activator of the coagulation cascade occurring in physiologic and pathologic conditions. Recent data suggest that human platelets might contain TF that is possibly derived from leukocytes. In this study, we investigated whether intraplatelet TF can be exposed on the membrane by platelet agonists. The modulation of this process by antiplatelet drugs has been evaluated as well. Methods and Results-Flow cytometric analysis of unstimulated platelets showed a small amount of membrane-associated immunoreactive TF (irTF) in whole blood, platelet-rich plasma, and washed platelets isolated from healthy subjects. ADP, thrombin receptor-activating peptide, and epinephrine significantly increased functionally active, membraneassociated irTF. ADP induced irTF exposure in a concentration-and time-dependent fashion. Agonist-induced irTF expression was completely inhibited by iloprost but not by aspirin. Interestingly, glycoprotein IIb/IIIa antagonists did not inhibit but rather potentiated the stimulatory effect of ADP on platelet irTF expression. Real-time polymerase chain reaction experiments showed detectable amounts of TF mRNA in unstimulated platelets. Conclusions-These findings indicate that platelet agonists and antiplatelet drugs might modulate platelet-associated irTF expression. Regulated TF expression establishes the potential for a previously unrecognized role for platelets in sustaining thrombus formation and growth via coagulation-mediated mechanisms. (Arterioscler Thromb Vasc Biol. 2003;23:1690-1696.)Key Words: platelets Ⅲ tissue factor Ⅲ coagulation Ⅲ thrombosis Ⅲ antiplatelet agents C linical and experimental evidence indicates that tissue factor (TF), a 47-kDa glycoprotein, triggers activation of the coagulation cascade that occurs in several human diseases, such as sepsis and other systemic conditions. 1 In addition, TF has been shown to be present in atherosclerotic plaques. 2,3 In particular, TF protein and activity have been found to be increased in coronary plaques, thus playing a crucial role in human coronary syndromes. 4 Vessel wallassociated TF, however, does not entirely explain the thrombogenic potential of vascular lesions when they are exposed to flowing blood. It has been proposed that thrombus growth might be promoted by circulating (ie, microparticle or platelet-associated) TF. 5 Indeed, to interact with plasma coagulation proteins and thus sustain thrombus growth, TF might diffuse from its source to the initial platelet layer. Because the time to capture any diffusing species increases as the square of distance, the shortened distance resulting from TF associated with circulating platelets might have very significant effects on subsequent reaction velocities.Considerable data now support the hypothesis that platelets actively modulate the propagation of coagulation by expressing specific, high-affinity receptors for coagulation proteases, zymogens, and cofactors that contribute to localize thrombin generation at the site of vascular injury. 6 It has be...

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