Comparison of shear stress-induced platelet microparticle formation and phosphatidylserine expression in presence of αIIbβ3 antagonists

The use of platelet glycoprotein IIb-IIIa (alpha(II)beta(3)) antagonists is an accepted practice in the treatment of acute coronary syndromes. Recent studies have demonstrated that alpha(IIb)beta(3) receptor antagonists are effective in inhibiting the procoagulant activity of platelets under static conditions. No investigation, however, has compared the ability of these platelet antagonists to inhibit platelet procoagulant activity, defined as an increase in phosphatidylserine (PS) expression, under conditions of shear stress. Thus, the goal of this study was to quantify the amount of microparticle formation and PS expression of platelets exposed to physiologic and pathophysiologic levels of shear stress in the absence and presence of three clinically approved parenteral alpha(IIb)beta(3) antagonists (abciximab, eptifibatide, and tirofiban). Flow cytometric results demonstrated that although microparticle formation was significantly inhibited by all three antagonists, PS expression by sheared platelets was affected differently depending on the antagonist present. Specifically, abciximab suppressed PS expression compared with the saline control; both abciximab and eptifibatide significantly reduced PS expression compared with tirofiban; and tirofiban potentiated PS expression relative to the saline control at the highest shear stress. This is the first demonstration of differential regulation of platelet PS expression and, by inference, procoagulant activity in the presence of alpha(IIbbeta3) receptor antagonists under shear stress. The current results may have future importance in improving the design of platelet antagonists as well as defining the general role of fluid shear stress in platelet thrombus formation.