caa a22 4500 475824415 CHVBK 20180406123827.0 cr unu---uuuuu 170329e20000801xx s 000 0 eng 10.1023/A:1018754906289 doi (NATIONALLICENCE)springer-10.1023/A:1018754906289 Inhibition of Platelet-Dependent Prothrombinase Activity and Thrombin Generation by Glycoprotein IIb/IIIa Receptor-Directed Antagonists: Potential Contributing Mechanism of Benefit in Acute Coronary Syndromes [Elektronische Daten] [Youfu Li, Frederick Spencer, Steven Ball, Richard Becker] The glycoprotein (GP) IIb/IIIa receptor antagonists used widely in the medical treatment of acute coronary syndromes and during percutaneous coronary interventions, prevent fibrinogen cross-linking and platelet aggregation, critical initiating steps in arterial thrombosis. Their anticoagulant properties, particularly when administered conjunctively with heparin preparations, are less well-characterized. In a series of in vitro studies, increasing concentrations of abciximab, tirofiban, and eptifibatide either alone or in combination with unfractionated heparin (UFH) or fractionated heparin (enoxaparin) were added to washed platelets suspended in Tyrode's buffer. Following platelet activation and prothrombinase assembly, thrombin generation was determined by enzyme-linked immunosorbent assay (ELISA). There was a concentration-dependent reduction in platelet-dependent thrombin generation with each of the GPIIb/IIIa receptor antagonists. The combination of tirofiban and UFH yielded percent, absolute and relative reductions (compared with tirofiban alone) of 48.0%, 16.9%, and 35.2%, respectively. The corresponding values for eptifibatide and abciximab were 38.0%, 13.5%, 35.5%, and 55.1%, 3.8%, 8.4%, respectively. Thrombin generation was decreased by an additional 2 to 3% (absolute reduction) with high concentrations of enoxaparin in combination with either eptifibatide or abciximab. Platelet GPIIb/IIIa receptor antagonists, beyond their ability to prevent fibrinogen-mediated aggregation, inhibit platelet-dependent prothrombinase activity and thrombin generation in a concentration-dependent manner. Heparin facilitates the existing anticoagulant properties, supporting combination therapy in clinical practice. The potential added benefit of fractionated heparin over UFH will require further investigation. Kluwer Academic Publishers, 2000 glycoprotein IIb/IIIa receptor antagonists nationallicence platelet aggregation nationallicence anticoagulants nationallicence unfractionated heparin nationallicence low-molecular-weight heparin nationallicence Li Youfu Laboratory for Vascular Biology Research, Cardiovascular Thrombosis Research Center, University of Massachusetts Medical School, Worcester, MA aut Spencer Frederick Laboratory for Vascular Biology Research, Cardiovascular Thrombosis Research Center, University of Massachusetts Medical School, Worcester, MA aut Ball Steven Laboratory for Vascular Biology Research, Cardiovascular Thrombosis Research Center, University of Massachusetts Medical School, Worcester, MA aut Becker Richard Laboratory for Vascular Biology Research, Cardiovascular Thrombosis Research Center, University of Massachusetts Medical School, Worcester, MA aut Journal of Thrombosis and Thrombolysis Kluwer Academic Publishers 10/1(2000-08-01), 69-76 0929-5305 10:1<69 2000 10 11239 https://doi.org/10.1023/A:1018754906289 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1018754906289 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Youfu Laboratory for Vascular Biology Research, Cardiovascular Thrombosis Research Center, University of Massachusetts Medical School, Worcester, MA aut NATIONALLICENCE 700 1- Spencer Frederick Laboratory for Vascular Biology Research, Cardiovascular Thrombosis Research Center, University of Massachusetts Medical School, Worcester, MA aut NATIONALLICENCE 700 1- Ball Steven Laboratory for Vascular Biology Research, Cardiovascular Thrombosis Research Center, University of Massachusetts Medical School, Worcester, MA aut NATIONALLICENCE 700 1- Becker Richard Laboratory for Vascular Biology Research, Cardiovascular Thrombosis Research Center, University of Massachusetts Medical School, Worcester, MA aut NATIONALLICENCE 773 0- Journal of Thrombosis and Thrombolysis Kluwer Academic Publishers 10/1(2000-08-01), 69-76 0929-5305 10:1<69 2000 10 11239 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer