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Thromb Haemost 2000; 84(03): 492-498
DOI: 10.1055/s-0037-1614050
Commentary
Schattauer GmbH

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

Authors

  • Mark I. Furman

    1   From the Center for Platelet Function Studies, Worcester, MA
    2   Division of Cardiovascular Medicine, Departments of Medicine, Worcester, MA

  • Lori A. Krueger

    1   From the Center for Platelet Function Studies, Worcester, MA
    3   Pediatrics, Worcester, MA

  • A. L. Frelinger III

    1   From the Center for Platelet Function Studies, Worcester, MA
    3   Pediatrics, Worcester, MA

  • Marc R. Barnard

    1   From the Center for Platelet Function Studies, Worcester, MA
    3   Pediatrics, Worcester, MA

  • Mary Ann Mascelli

    5   Centocor, Inc., Malvern PA, USA

  • Marian T. Nakada

    5   Centocor, Inc., Malvern PA, USA

  • Alan D. Michelson

    1   From the Center for Platelet Function Studies, Worcester, MA
    3   Pediatrics, Worcester, MA
    4   Surgery, University of Massachusetts Medical School, Worcester, MA

Funded in part by Centocor, Inc., Malvern, PA.
Further Information

Publication History

Received 07 January 2000

Accepted after resubmission 14 April 2000

Publication Date:
14 December 2017 (online)

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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.

Key words

Platelets - coagulation - glycoproteins - platelet aggregation inhibitors - anticoagulants
 

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