Novel assay based on diluted prothrombin time reflects anticoagulant effects of direct oral factor Xa inhibitors: Results of multicenter study in Japan
Novel assay based on diluted prothrombin time reflects anticoagulant effects of direct oral factor Xa inhibitors: Results of multicenter study in Japan
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DOI：
10.1016/j.thromres.2020.07.020
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发表时间：
2020-11-01
影响因子：
7.5
通讯作者：
Takahashi, Nobuhiko
中科院分区：
文献类型：
--
作者：
Ieko, Masahiro;Ohmura, Kazumasa;Takahashi, Nobuhiko
背景：直接口服抗凝剂靶向因子Xa(DXaIs)用于预防各种静脉血栓疾病，不需要常规监测。然而，为了预防严重事件，包括大出血和/或难治性血栓，有必要评估它们的抗凝效果。目的：我们研究了一种基于稀释凝血酶原时间(DPT)的新方法测定的抑制凝血酶生成(RITG)比率与凝血标志物和显示药物效果的实验室测试结果的相关性。此外，还研究了RITG作为DXaI治疗确认试验的有效性。方法：柠檬化血浆样本来自日本4个不同机构的利伐沙班(n=882)、阿皮沙班(n=1214)或依多沙班(n=820)治疗的患者。结果：在DXaI组中，RITG与凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、D-二聚体及血浆D-二聚体浓度呈正相关，与D-二聚体呈负相关。RITG在峰值和低谷期的波动反映了每个DXaI的抗凝活性特征，这与血药浓度波动不同。RITG在血栓形成患者中显著降低，而在出血患者中显著升高。结论：我们开发了一种基于DPT的新的RITG测量方法。RITG代表血浆样本中残留的凝血能力，有助于评估DXaI患者的出血和血栓形成倾向。RITG可用于证实DXaI类药物口服抗凝治疗的有效性。
Background: Direct oral anticoagulants targeting factor Xa (DXaIs) are administered as prophylaxis for various venothrombotic diseases without routine monitoring required. However, assessment of their anticoagulant effects is necessary to prevent severe events, including major bleeding and/or refractory thrombosis.Objectives: We examined the correlation of ratio of inhibited thrombin generation (RITG), determined using a novel assay based on dilute prothrombin time (dPT), with coagulant markers and laboratory test results to show drug effects. In addition, RITG usefulness as a confirmation test for DXaI therapy was investigated.Methods: Citrated plasma samples were obtained from patients treated with rivaroxaban (n = 882), apixaban (n = 1214), or edoxaban (n = 820) at 4 different institutions in Japan. Laboratory tests, including prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, and plasma concentrations of DXaIs, were conducted, with drug concentrations divided into peak and trough groups, within and after 5 h of administration.Results: In each DXaI group, RITG was positively correlated with PT, APTT, and drug concentration, and negatively with D-dimer. RITG fluctuation during the peak and trough periods reflected the anticoagulant activity characteristic of each DXaI, which was different from blood concentration fluctuations. RITG showed a significant decrease in cases with thrombosis, while that was increased in those with hemorrhage.Conclusion: We developed RITG, a novel measurement method based on dPT. RITG represents residual coagulation ability in plasma samples, and is useful for assessment of bleeding and thrombotic tendencies in DXaI patients. RITG can be utilized to confirm the effectiveness of oral anticoagulation therapy with DXaI agents.