Department of Cardiology, Medical Department IV, University Hospital Leipzig, Leipzig, Germany.
Medical faculty, University Hospital, Leipzig, Germany.
Int J Lab Hematol. 2021 Dec;43(6):1539-1548. doi: 10.1111/ijlh.13618. Epub 2021 Jun 7.
The antithrombotic effect of direct oral anticoagulants (DOAC) in specific clinical scenarios is difficult to assess.
This study aimed to evaluate the effect of DOAC on thrombin generation (TG) in relation to their plasma level.
Eighty patients newly started on anticoagulation were included, 20 patients for each DOAC-apixaban, edoxaban, rivaroxaban, and dabigatran. Plasma was sampled before DOAC (baseline), at plasma peak time, 6 and 12 hours after starting DOAC for quantification of drug levels and TG.
The baseline TG before DOAC intake showed inter-individual variability. All DOACs significantly prolonged lag time (LT) and time to peak (TTP), but did not change endogenous thrombin potential (ETP). Anti-Xa inhibitors but not dabigatran reduced thrombin peak, but the effect of apixaban at plasma peak was less pronounced (factor 1.6). LT and TTP prolongation of dabigatran was lower compared to anti-Xa inhibitors. All DOACs showed a nonlinear dose-response relationship, with the greatest antithrombotic effect at lower DOAC plasma levels. The inhibition of TG parameters between baseline and peak was parallel between individual patients but the coefficient of variation of TG was lower compared to drug levels.
The antithrombotic effect at DOAC peak plasma level measured by TG depends on the patient-specific baseline TG level and the drug-specific inhibition by the particular DOAC. Although peak plasma levels have a high variability, the variation of TG is lower compared to drug levels. Therefore, TG assays may be superior to plasma levels in the assessment of the intensity of anticoagulation.
直接口服抗凝剂（DOAC）在特定临床情况下的抗栓效果难以评估。
本研究旨在评估 DOAC 对凝血酶生成（TG）的影响与其血浆水平的关系。
共纳入 80 例新开始抗凝治疗的患者，每个 DOAC（阿哌沙班、依度沙班、利伐沙班和达比加群）组各 20 例。在开始 DOAC 前（基线）、达峰时、开始 DOAC 后 6 小时和 12 小时采集血浆，用于药物水平和 TG 的定量检测。
DOAC 摄入前的基线 TG 存在个体间变异性。所有 DOAC 均显著延长了 lag time（LT）和达到峰值时间（TTP），但不改变内源性凝血酶潜能（ETP）。抗 Xa 抑制剂而非达比加群降低了凝血酶峰值，但阿哌沙班在血浆达峰时的效果不那么明显（倍数 1.6）。与抗 Xa 抑制剂相比，达比加群的 LT 和 TTP 延长程度较低。所有 DOAC 均显示出非线性剂量反应关系，在较低的 DOAC 血浆水平下具有最大的抗栓作用。在个体患者之间，TG 各参数从基线到峰值的抑制作用是平行的，但 TG 的变异系数比药物水平低。
通过 TG 测量的 DOAC 峰值血浆水平的抗栓效果取决于患者特定的基线 TG 水平和特定 DOAC 的抑制作用。尽管峰值血浆水平具有较高的变异性，但 TG 的变化比药物水平低。因此，TG 检测可能优于血浆水平，用于评估抗凝强度。
