Combined Effects of Eptifibatide and Anticoagulants: Differences between LMWH and UH or rH in Thrombin Generation Inhibition but not in Platelet Aggregation Inhibition

Martin Koestenberger; Siegfried Gallistl; Gerhard Cvirn; Birgit Roschitz; Martina Petritsch; Bettina Leschnik; Wolfgang Muntean

doi:10.1055/s-0037-1613348

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2002; 88(06): 1012-1019
DOI: 10.1055/s-0037-1613348

Involvement of Thrombin Receptors in the Subject-dependent Variability in Ca2+ Signal Generation

Schattauer GmbH

Combined Effects of Eptifibatide and Anticoagulants: Differences between LMWH and UH or rH in Thrombin Generation Inhibition but not in Platelet Aggregation Inhibition

Martin Koestenberger

¹Department of Pediatrics, Haemostasis and Thrombosis, University of Graz, Austria

²Ludwig Boltzmann Research Institute for Pediatric Haemostasis and Thrombosis, University of Graz, Austria

,

Siegfried Gallistl

¹Department of Pediatrics, Haemostasis and Thrombosis, University of Graz, Austria

²Ludwig Boltzmann Research Institute for Pediatric Haemostasis and Thrombosis, University of Graz, Austria

,

Gerhard Cvirn

²Ludwig Boltzmann Research Institute for Pediatric Haemostasis and Thrombosis, University of Graz, Austria

,

Birgit Roschitz

²Ludwig Boltzmann Research Institute for Pediatric Haemostasis and Thrombosis, University of Graz, Austria

,

Martina Petritsch

²Ludwig Boltzmann Research Institute for Pediatric Haemostasis and Thrombosis, University of Graz, Austria

,

Bettina Leschnik

¹Department of Pediatrics, Haemostasis and Thrombosis, University of Graz, Austria

,

Wolfgang Muntean

¹Department of Pediatrics, Haemostasis and Thrombosis, University of Graz, Austria

²Ludwig Boltzmann Research Institute for Pediatric Haemostasis and Thrombosis, University of Graz, Austria

› Institutsangaben

Abstract

Summary

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.

Keywords

Simultaneous determination - thrombin generation - platelet aggregation - eptifibatide - LMWH.

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