Department of Cardiology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, 920-0293, Japan.
Central Clinical Laboratoy, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, 920-0293, Japan.
J Thromb Thrombolysis. 2020 Aug;50(2):371-379. doi: 10.1007/s11239-020-02079-7.
Factor Xa (FXa) inhibitors are recommended for use in fixed doses without laboratory monitoring. However, prior studies reported the importance of establishing biomarkers representing anticoagulation intensity related to bleeding or thrombotic events. To test the hypothesis that prothrombin activation fragment 1 and 2 (F1 + 2), a non-specific marker of thrombin generation, could be altered during FXa inhibitor treatment in patients with atrial fibrillation. We conducted the study in two different clinical settings. First, the interrelations among biomarkers representing coagulation/fibrinolysis were investigated in 80 patients in an outpatient clinic. Second, these biomarkers were evaluated in 75 patients who underwent radiofrequency catheter ablation. Plasma concentration of FXa inhibitors was evaluated using an anti-FXa chromogenic assay (C-Xa). In the outpatient study, only F1 + 2 exhibited a significant and negative association with C-Xa (rS = - 0.315, p = 0.026), and 37% of the variance could be explained by C-Xa levels. F1 + 2 levels above the reference range (> 229 pmol/L) could be considered as a cut-off to identify poor patient compliance or under-dosing. In the peri-ablation study, increased F1 + 2 levels were associated with decline of C-Xa levels after periprocedural discontinuation of FXa inhibitors, which was greater in the rivaroxaban group than in the apixaban group. F1 + 2 showed modest and inverse association with plasma concentration of rivaroxaban and apixaban in patients with atrial fibrillation. Larger study to test the hypothesis that continued thrombin generation despite anticoagulation is associated with a heightened risk of clinical events is required.
Xa 因子（FXa）抑制剂推荐固定剂量使用，无需实验室监测。然而，先前的研究报告了确定代表抗凝强度与出血或血栓事件相关的生物标志物的重要性。为了检验在心房颤动患者中，凝血酶生成的非特异性标志物凝血酶原激活片段 1 和 2（F1+2）在 FXa 抑制剂治疗期间可能发生改变的假说，我们在两个不同的临床环境中进行了研究。首先，在 80 名门诊患者中研究了代表凝血/纤溶的生物标志物之间的相互关系。其次，在接受射频导管消融术的 75 名患者中评估了这些生物标志物。使用抗 FXa 显色测定法（C-Xa）评估 FXa 抑制剂的血浆浓度。在门诊研究中，只有 F1+2 与 C-Xa 呈显著负相关（rS=−0.315，p=0.026），C-Xa 水平可以解释 37%的差异。F1+2 水平高于参考范围（>229 pmol/L）可被视为识别患者依从性差或剂量不足的临界点。在消融前研究中，F1+2 水平升高与 FXa 抑制剂治疗后围手术期停药后 C-Xa 水平下降相关，利伐沙班组比阿哌沙班组下降更大。在接受心房颤动治疗的患者中，F1+2 与利伐沙班和阿哌沙班的血浆浓度呈适度的负相关。需要更大的研究来检验尽管抗凝但持续的血栓生成与临床事件风险增加相关的假说。
