Effects of the glycoprotein IIb/IIIa receptor antagonist c7E3 Fab and anticoagulants on platelet aggregation and thrombin potential under high coagulant challenge in vitro.
The present study was performed to investigate the combined effects of the platelet glycoprotein IIb/IIIa receptor antagonist c7E3 Fab (abciximab) and the anticoagulants unfractionated heparin (UH), low molecular weight heparin (LMWH), and recombinant hirudin (rH) on platelet aggregation and thrombin generation under high coagulant challenge by extrinsic activation of platelet-rich plasma. Platelet aggregation and thrombin generation were assessed simultaneously in the presence of different concentrations of abciximab and anticoagulants. Increasing concentrations of abciximab resulted in a dose-dependent anti-aggregating effect with a maximum at 20 microg/ml. Doses of 5, 10, and 20 microg/ml abciximab prolonged the lag phase until the onset of platelet aggregation, but this effect was independent of the dosage used. Abciximab had no influence on the thrombin potential under our high coagulant challenge. UH, LMWH, and rH showed a dose-dependent prolongation of the lag phase until the onset of platelet aggregation and decreased the thrombin potential. Addition of anticoagulants did not contribute to further inhibition of platelet aggregation in the presence of abciximab, but the combination of abciximab and anticoagulants exhibited an additive effect on prolongation of the lag phase until the onset of platelet aggregation. Addition of abciximab to anticoagulants did not result in further decrease of the thrombin potential. Our study demonstrates the respective specific effects of abciximab and anticoagulants on platelet aggregation and thrombin potential under high coagulant challenge, and also an additive effect of abciximab and the anticoagulants UH, LMWH, and rH on the lag phase until the onset of platelet aggregation.
Department of Pediatrics, Ludwig Boltzmann Research Institute for Pediatric Haemostasis and Thrombosis, University of Graz, Austria.
M
M
Koestenberger
S
S
Gallistl
G
G
Cvirn
B
B
Roschitz
W
W
Muntean
D000077284:Abciximab; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology*; D003029:Coagulants / Q000494:pharmacology*; D017985:Dalteparin / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D007700:Kinetics; D009391:Nephelometry and Turbidimetry; D010949:Plasma; D010974:Platelet Aggregation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D003029:Coagulants; D006629:Hirudins; D007140:Immunoglobulin Fab Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; D013917:Thrombin; D017985:Dalteparin; D000077284:Abciximab