title: Combined effects of eptifibatide and anticoagulants: differences between LMWH and UH or rH in thrombin generation inhibition but not in platelet aggregation inhibition.
abstract: Aim of our study was to investigate effects of eptifibatide and anticoagulants on platelet aggregation and thrombin generation under low and high coagulant challenge in tissue factor-activated platelet rich plasma using a model allowing simultaneous determination of the time course of platelet aggregation and thrombin generation. Eptifibatide exerted a dose-dependent anti-aggregating effect under both high and significantly stronger under low coagulant challenge. Combination of eptifibatide and anticoagulants resulted in significant additive prolongation of the lag phase until the onset of platelet aggregation, more pronounced under low coagulant challenge. Under high, but not under low coagulant challenge combination of eptifibatide and anticoagulants had a significant synergistic inhibitory effect on platelet aggregation. Under low coagulant challenge combination of eptifibatide with LMWH, but not with UH, or rH, resulted in significantly reduced thrombin potential, F 1+2 generation, and FXa formation compared to measurements in the absence of eptifibatide. We demonstrate a synergistic effect of eptifibatide and anticoagulants on platelet aggregation inhibition and an additional inhibitory effect of LMWH and eptifibatide on thrombin generation. Our results support the notion that combination of eptifibatide and anticoagulants might be beneficial in atherosclerotic disease to palliate the thrombogenic potency of ruptured atherosclerotic plaques.
authors.affiliation: Department of Pediatrics, University of Graz, Austria. koestenbergerm@hotmail.com
authors.forename: Martin
authors.initials: M
authors.lastname: Koestenberger
authors.forename: Siegfried
authors.initials: S
authors.lastname: Gallistl
authors.forename: Gerhard
authors.initials: G
authors.lastname: Cvirn
authors.forename: Birgit
authors.initials: B
authors.lastname: Roschitz
authors.forename: Martina
authors.initials: M
authors.lastname: Petritsch
authors.forename: Bettina
authors.initials: B
authors.lastname: Leschnik
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Muntean
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage*; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy; D004357:Drug Synergism; D000077542:Eptifibatide; D015951:Factor Xa / Q000096:biosynthesis; D006493:Heparin / Q000008:administration & dosage; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage; D006629:Hirudins / Q000008:administration & dosage; D006801:Humans; D066298:In Vitro Techniques; D010455:Peptides / Q000008:administration & dosage*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D013917:Thrombin / Q000096:biosynthesis*; D013927:Thrombosis / Q000517:prevention & control
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D006629:Hirudins; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D006493:Heparin; D013917:Thrombin; D015951:Factor Xa; D000077542:Eptifibatide