GPIIb-IIIa antagonist-induced reduction in platelet surface factor V/Va binding and phosphatidylserine expression in whole blood

In addition to inhibition of platelet aggregation, GPIIb-IIIa antagonists m ay reduce thrombotic events via other mechanisms. In a novel whole blood fl ow cytometric system, we investigated the effects of GPIIb-IIIa antagonists , in the presence or absence of thrombin inhibitors, on platelet surface-bo und factor V/Va and platelet surface phospholipids.: Diluted venous blood w as incubated with either buffer or a GPIIb-IIIa antagonist (abciximab, tiro fiban, or eptifibatide). Some samples were pre-incubated with clinically re levant concentrations of unfractionated heparin (UFH), a low molecular weig ht heparin, a direct thrombin inhibitor, or buffer only. Platelets were the n activated and labeled with mAb V237 (factor V/Va-specific) or annexin V ( binds phosphatidylserine), fixed, and analyzed by flow cytometry. In the ab sence of thrombin inhibitors, GPIIb-IIIa antagonists (especially abciximab) significantly reduced agonist-induced platelet procoagulant activity, as d etermined by reduced binding of V237 and annexin V. At high pharmacologic c oncentrations, unfractionated heparin and enoxaparin, but not hirudin, furt her reduced factor V/Va binding to the surface of activated platelets in th e presence of GPIIb-IIIa antagonists. Agonist-induced platelet procoagulant activity was reduced in a patient with Glanzmann's thrombasthenia. We conc lude that GPIIb-IIIa antagonists reduce platelet procoagulant activity in w hole blood and heparin and enoxaparin augment this reduction. Fibrinogen bi nding to GPIIb-IIIa is important in the generation of platelet procoagulant activity.