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

Thromb Haemost. 2000 Sep;84(3):492-8.


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-IIa 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abciximab
  • Antibodies, Monoclonal / pharmacology
  • Blood Platelets / metabolism
  • Collagen / pharmacology
  • Dose-Response Relationship, Drug
  • Eptifibatide
  • Factor V / metabolism*
  • Flow Cytometry
  • Humans
  • Immunoglobulin Fab Fragments / pharmacology
  • Infant, Newborn
  • Membrane Proteins / metabolism
  • Peptides / pharmacology
  • Phosphatidylserines / blood*
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Protein Binding
  • Thrombasthenia / blood
  • Thrombin / antagonists & inhibitors
  • Thrombin / pharmacology
  • Tirofiban
  • Tyrosine / analogs & derivatives*
  • Tyrosine / pharmacology


  • Antibodies, Monoclonal
  • Immunoglobulin Fab Fragments
  • Membrane Proteins
  • Peptides
  • Phosphatidylserines
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Tyrosine
  • Factor V
  • Collagen
  • Thrombin
  • Tirofiban
  • Eptifibatide
  • Abciximab