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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

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
› Author AffiliationsFunded 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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