Effects on platelet function of a direct acting antagonist of coagulation factor Xa
Effects on platelet function of a direct acting antagonist of coagulation factor Xa
复制标题
凝血因子 Xa 直接拮抗剂对血小板功能的影响
DOI：
10.1007/s11239-012-0727-5
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发表时间：
2012
影响因子：
4
通讯作者：
D. Schneider
中科院分区：
文献类型：
--
作者：
Sukit M. Ringwala;Peter M Dibattiste;D. Schneider
由于新型直接作用抗凝剂正在心血管事件的二级预防中进行测试，我们评估了Xa因子直接作用拮抗剂对血小板功能的潜在影响。来自用阿司匹林但没有其他抗血栓形成剂治疗的患有已知冠状动脉疾病的患者的血液在体外掺入单独的利伐沙班或与直接作用的P2 Y12拮抗剂（坎格雷洛）的组合。为了限制抗凝剂的共同作用并使凝血因子之间能够相互作用，仅使用因子XIIa的特异性抑制剂玉米胰蛋白酶抑制剂对血液进行抗凝。用肽GPRP防止纤维蛋白的聚合。使用流式细胞术测定血小板对脂化组织因子、凝血酶、胶原模拟物惊厥素和二磷酸腺苷（ADP）的活化。利伐沙班抑制由组织因子诱导的血小板活化，并在较小程度上抑制由凝血酶诱导的活化，当与坎格雷洛组合时，该作用加重。利伐沙班没有减弱惊厥素诱导的血小板活化;然而，在利伐沙班抗凝的血液中观察到ADP诱导的血小板活化的有限但一致的减弱。利伐沙班对ADP诱导的血小板活化的影响不受凝血酶、组织因子或血小板-白细胞聚集的介导。总之，利伐沙班在体外减弱凝血酶介导的血小板活化。鉴于凝血酶在动脉粥样硬化斑块破裂后血小板活化中的关键作用，利伐沙班应减弱体内血小板活化，与P2 Y12拮抗剂联合使用可增强该作用。
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.
影响因子：
20.3
作者：
Rand, MD;Lock, JB;Mann, KG
通讯作者：
Mann, KG