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GPIIb-IIIa Antagonist-induced Reduction in Platelet Surface Factor V/Va Binding and Phosphatidylserine Expression in Whole Blood

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Issue: 2000: 84/3 (Sept) pp.362-522
Pages: 492-498

GPIIb-IIIa Antagonist-induced Reduction in Platelet Surface Factor V/Va Binding and Phosphatidylserine Expression in Whole Blood

Mark I. Furman (1), (2) , Lori A. Krueger (1), (3) , A. L. Frelinger III (1), (3) , Marc R. Barnard (1), (3) , Mary Ann Mascelli (5) , Marian T. Nakada (5) , Alan D. Michelson (1), (3), (4)
From the (1) Center for Platelet Function Studies, (2) Division of Cardiovascular Medicine, Departments of Medicine, (3) Pediatrics and (4) Surgery , University of Massachusetts Medical School, Worcester, MA and (5) Centocor, Inc., Malvern PA, USA

Summary

In addition to inhibition of platelet aggregation, GPIIb-IIIa antagonists may reduce thrombotic events via other mechanisms. In a novel whole blood flow cytometric system, we investigated the effects of GPIIb-IIIa antagonists, in the presence or absence of thrombin inhibitors, on platelet surface-bound factor V/Va and platelet surface phospholipids. Diluted venous blood was incubated with either buffer or a GPIIb-IIIa antagonist (abciximab, tirofiban, or eptifibatide). Some samples were pre-incubated with clinically relevant concentrations of unfractionated heparin (UFH), a low molecular weight heparin, a direct thrombin inhibitor, or buffer only. Platelets were then activated and labeled with mAb V237 (factor V/Va-specific) or annexin V (binds phosphatidylserine), fixed, and analyzed by flow cytometry. In the absence of thrombin inhibitors, GPIIb-IIIa antagonists (especially abciximab) significantly reduced agonist-induced platelet procoagulant activity, as determined by reduced binding of V237 and annexin V. At high pharmacologic concentrations, unfractionated heparin and enoxaparin, but not hirudin, further reduced factor V/Va binding to the surface of activated platelets in the presence of GPIIb-IIIa antagonists. Agonist-induced platelet procoagulant activity was reduced in a patient with Glanzmann’s thrombasthenia. We conclude that GPIIb-IIIa antagonists reduce platelet procoagulant activity in whole blood and heparin and enoxaparin augment this reduction. Fibrinogen binding to GPIIb-IIIa is important in the generation of platelet procoagulant activity.