Division of Hemostaseology, Medical Department I, University Hospital Leipzig, Leipzig, Germany.
MVZ Limbach Magdeburg, Lab Dr. Franke, Bönigk and Colleagues, Center of Coagulation Disorders and Vascular Diseases, Magdeburg, Germany.
Int J Lab Hematol. 2022 Feb;44(1):193-201. doi: 10.1111/ijlh.13721. Epub 2021 Sep 29.
Monitoring of direct oral anticoagulants (DOACs) with calibrated anti-Xa assay is limited by the high intra- and interindividual variations of the test results. Thrombin generation (TG) is a global hemostatic assay that reflects the patient´s individual coagulation status. The aim of this study was to investigate the influence of DOACs on TG measured with a fully automated assay system.
All consecutive patients under apixaban and rivaroxaban coming to the outpatient coagulation center MVZ Limbach, Magdeburg, Germany between October 2017 and April 2020 were included. DOAC plasma levels were correlated with TG assessed using the fully automated Ceveron TG analyzer.
A total of 703 rivaroxaban and 252 apixaban containing plasma samples were included. There was a significant correlation between DOAC plasma levels and all TG parameters except for lag time regarding apixaban. Time to peak and peak thrombin followed an exponential regression curve, while this was linear for the endogenous thrombin potential (ETP). Apixaban showed a lower correlation coefficient for all TG parameters compared with rivaroxaban, and thrombin generation was less influenced by apixaban than rivaroxaban at plasma levels >100 ng/ml. The sensitivity and negative predictive value of normal TG parameters for the prediction of DOAC plasma levels <30 ng/ml was >85%.
The present data show a moderate predominantly nonlinear correlation between TG parameters and plasma levels of apixaban and rivaroxaban. Rivaroxaban has a stronger effect on TG than apixaban.
使用校准的抗-Xa 测定法监测直接口服抗凝剂（DOAC）受到测试结果个体内和个体间高度变化的限制。血栓生成（TG）是一种反映患者个体凝血状态的整体止血测定法。本研究旨在探讨 DOAC 对使用全自动测定系统测量的 TG 的影响。
纳入 2017 年 10 月至 2020 年 4 月期间在德国马格德堡 MVZ Limbach 门诊凝血中心就诊的所有连续接受阿哌沙班和利伐沙班治疗的患者。将 DOAC 血浆水平与使用全自动 Ceveron TG 分析仪评估的 TG 相关联。
共纳入 703 例利伐沙班和 252 例阿哌沙班含血浆样本。除阿哌沙班的滞后时间外，DOAC 血浆水平与所有 TG 参数均呈显著相关。达峰时间和最大血栓生成量呈指数回归曲线，而内源性血栓生成潜力（ETP）则呈线性关系。与利伐沙班相比，阿哌沙班的所有 TG 参数的相关系数均较低，并且在血浆水平>100ng/ml 时，阿哌沙班对血栓生成的影响小于利伐沙班。正常 TG 参数预测 DOAC 血浆水平<30ng/ml 的敏感性和阴性预测值>85%。
本研究数据表明，阿哌沙班和利伐沙班的 TG 参数与血浆水平之间存在中度且主要是非线性的相关性。利伐沙班对 TG 的影响大于阿哌沙班。
