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
