Effects on platelet function of a direct acting antagonist of coagulation factor Xa

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• 作者：Sukit M. Ringwala (1) sukit.ringwala@vtmednet.org
  Peter M. DiBattiste (2)
  David J. Schneider (1)
• 关键词：Platelet function testing – ; Anticoagulant – ; Antiplatelet agent – ; Thrombin
• 刊名：Journal of Thrombosis and Thrombolysis
• 出版年：2012
• 出版时间：October 2012
• 年：2012
• 卷：34
• 期：3
• 页码：291-296
• 全文大小：300.7 KB
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• 作者单位：1. Cardiovascular Unit and Cardiovascular Research Institute, University of Vermont, 111 Colchester Ave, Burlington, VT 05401, USA2. Johnson & Johnson Pharmaceutical Research and Development, Raritan, NJ, USA
• ISSN：1573-742X

文摘

Because novel direct acting anticoagulants are being tested in the secondary prevention of cardiovascular events, we assessed potential effects of a direct acting antagonist of Factor Xa on platelet function. Blood from patients with known coronary artery disease who were treated with aspirin but no other antithrombotic agent was spiked in vitro with rivaroxaban alone or in combination with a direct acting P2Y12 antagonist (cangrelor). To limit cofounding effects of anticoagulants and to enable interaction between coagulation factors, blood was anticoagulated only with a specific inhibitor of Factor XIIa, corn trypsin inhibitor. Polymerization of fibrin was prevented with the peptide GPRP. Activation of platelets was determined with the use of flow cytometry in response to lipidated tissue factor, thrombin, the collagen mimetic convulxin, and adenosine diphosphate (ADP). Rivaroxaban inhibited the activation of platelets induced by tissue factor and to a lesser extent activation induced by thrombin, effects that were accentuated when combined with cangrelor. Rivaroxaban did not attenuate convulxin-induced activation of platelets; however, a limited but consistent attenuation of ADP-induced platelet activation was seen with blood anticoagulated with rivaroxaban. Effects of rivaroxaban on ADP-induced platelet activation were not mediated by thrombin, tissue factor, or platelet-leukocyte aggregation. In conclusion, rivaroxaban attenuated in vitro the activation of platelets mediated by thrombin. In light of the pivotal role of thrombin in platelet activation after rupture of an atherosclerotic plaque, rivaroxaban should attenuate platelet activation in vivo, an effect that is accentuated by combination with a P2Y12 antagonist.