title: Comparison of shear stress-induced platelet microparticle formation and phosphatidylserine expression in presence of alphaIIbbeta3 antagonists.
abstract: The use of platelet glycoprotein IIb-IIIa (alphaIIbbeta3) antagonists is an accepted practice in the treatment of acute coronary syndromes. Recent studies have demonstrated that alpha beta 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 beta 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 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.
authors.affiliation: Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Haga
authors.forename: Steven M
authors.initials: SM
authors.lastname: Slack
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Jennings
mesh_terms: D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D010718:Phosphatidylserines / Q000096:biosynthesis* / Q000235:genetics; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000502:physiology; D033081:Shear Strength; D013314:Stress, Mechanical
chemical_list: D010718:Phosphatidylserines; D019039:Platelet Glycoprotein GPIIb-IIIa Complex