caa a22 4500 475824105 CHVBK 20180406123826.0 cr unu---uuuuu 170329e20000401xx s 000 0 eng 10.1023/A:1018710526772 doi (NATIONALLICENCE)springer-10.1023/A:1018710526772 Enoxaparin, a Low Molecular Weight Heparin, Inhibits Platelet-Dependent Prothrombinase Assembly and Activity by Factor-Xa Neutralization [Elektronische Daten] [Frederick Spencer, Steven Ball, Qiliang Zhang, Longbin Liu, Stephen Benoit, Richard Becker] Background: The available evidence suggests strongly that intravascular thrombosis is mediated predominantly by tissue-factor and its activation of factor X, which in the presence of factor Va, calcium, and phospholipid (prothrombinase complex) effectively converts prothrombin to thrombin. In vitro experiments have shown that low molecular weight heparins (LMWHs) have greater anti-Xa activity than unfractionated heparin; however, it remains unclear as to whether their antithrombotic effects in vivo are determined by a similar mechanism. We determined the ability of plasma obtained from patients with either unstable angina or non-ST segment elevation myocardial infarction (MI) receiving the LMWH enoxaparin (anti Xa:IIa ratio 3:1) to inhibit tissue factor-mediated thrombin generation and to inactivate platelet prothrombinase. Methods: Platelet rich plasma was prepared by suspending washed donor platelets in the plasma of 7 patients participating in the TIMI 11A study. Samples were obtained before, 1 hour after a 30-mg IV bolus of enoxaparin and 6 hours after the third subcutaneous injection (1.0-1.25 mg/kg given subcutaneously every 12 hrs). Tissue factor (0.1 ng/ml) and 10 mM CaCl2 were added to initiate extrinsic coagulation. At timed intervals prothrombin activation fragment 1.2 (F1.2) levels (thrombin generation) were measured using an ELISA technique. Inactivation of reformed platelet prothrombinase by samples obtained at the same time points was also determined. Results: Patient plasma obtained 1 hr after treatment initiation and 6 hours after the third subcutaneous injection inhibited tissue factor mediated prothrombinase assembly by 31% and 11%, respectively and platelet prothrombinase activity by 27% and 22%, respectively. Conclusion: We conclude that enoxaparin in plasma concentrations achieved routinely in clinical practice is able to: (1) inhibit tissue factor mediated extrinsic coagulation by preventing platelet surface prothrombinase assembly, and (2) inactivate platelet prothrombinase activity and resulting thrombin generation. These observations suggest that a LMWH's anti-Xa activity (and anti-Xa:IIa profile) is important in determining its overall antithrombotic potential. Clinical trials comparing agents with differing anti-Xa:IIa properties will be required, however, to provide proof of concept. Kluwer Academic Publishers, 2000 enoxaparin nationallicence low molecular weight heparin nationallicence prothrombinase nationallicence acute coronary syndrome nationallicence Spencer Frederick Cardiovascular Thrombosis Research Center, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA aut Ball Steven Cardiovascular Thrombosis Research Center, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA aut Zhang Qiliang Cardiovascular Thrombosis Research Center, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA aut Liu Longbin Cardiovascular Thrombosis Research Center, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA aut Benoit Stephen Cardiovascular Thrombosis Research Center, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA aut Becker Richard Cardiovascular Thrombosis Research Center, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA aut Journal of Thrombosis and Thrombolysis Kluwer Academic Publishers 9/3(2000-04-01), 223-228 0929-5305 9:3<223 2000 9 11239 https://doi.org/10.1023/A:1018710526772 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1018710526772 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Spencer Frederick Cardiovascular Thrombosis Research Center, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA aut NATIONALLICENCE 700 1- Ball Steven Cardiovascular Thrombosis Research Center, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA aut NATIONALLICENCE 700 1- Zhang Qiliang Cardiovascular Thrombosis Research Center, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA aut NATIONALLICENCE 700 1- Liu Longbin Cardiovascular Thrombosis Research Center, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA aut NATIONALLICENCE 700 1- Benoit Stephen Cardiovascular Thrombosis Research Center, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA aut NATIONALLICENCE 700 1- Becker Richard Cardiovascular Thrombosis Research Center, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA aut NATIONALLICENCE 773 0- Journal of Thrombosis and Thrombolysis Kluwer Academic Publishers 9/3(2000-04-01), 223-228 0929-5305 9:3<223 2000 9 11239 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer