GPIIb-IIIa antagonist-induced reduction in platelet surface factor V/Va binding and phosphatidylserine expression in whole blood
Department of Pediatrics
Antibodies, Monoclonal; Blood Platelets; Collagen; Dose-Response Relationship, Drug; Factor V; Flow Cytometry; Humans; Immunoglobulin Fab Fragments; Infant, Newborn; Membrane Proteins; Peptides; Phosphatidylserines; Platelet Glycoprotein GPIIb-IIIa Complex; Protein Binding; Thrombasthenia; Thrombin; Tyrosine
Hematology | Oncology | Pediatrics
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.
Thromb Haemost. 2000 Sep;84(3):492-8.
Thrombosis and haemostasis
Furman, Mark I.; Krueger, Lori A.; Frelinger, Andrew L. III; Barnard, Marc R.; Mascelli, Mary Ann; Nakada, Marian T.; and Michelson, Alan D., "GPIIb-IIIa antagonist-induced reduction in platelet surface factor V/Va binding and phosphatidylserine expression in whole blood" (2000). Hematology/Oncology. 23.