Division of Cardiovascular Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
Department of Thromboembolic Disorders, Institute of Cardiology, Medical College, John Paul II Hospital, Jagiellonian University, Kraków, Poland.
Scand J Clin Lab Invest. 2024 Jul;84(4):257-267. doi: 10.1080/00365513.2024.2369993. Epub 2024 Jul 2.
There are important pharmacological differences between direct oral anticoagulants (DOAC) and a deeper knowledge of how they influence different aspects of hemostasis in patients on treatment is desirable.
Blood samples from patients on dabigatran ( = 23), rivaroxaban ( = 26), or apixaban ( = 20) were analyzed with a fibrin network permeability assay, a turbidimetric clotting and lysis assay, the calibrated automated thrombogram (CAT), plasma levels of thrombin-antithrombin complex (TAT) and D-dimer, as well as DOAC concentrations, PT-INR and aPTT. As a comparison, we also analyzed samples from 27 patients on treatment with warfarin.
Patients on dabigatran had a more permeable fibrin network, longer lag time (CAT and turbidimetric assay), and lower levels of D-dimer in plasma, compared with patients on rivaroxaban- and apixaban treatment, and a more permeable fibrin network than patients on warfarin. Clot lysis time was slightly longer in patients on dabigatran than in patients on rivaroxaban. Warfarin patients formed a more permeable fibrin network than patients on apixaban, had longer lag time than patients on rivaroxaban (CAT assay), and lower peak thrombin and ETP compared to patients on treatment with both FXa-inhibitors.
Results from this study indicate dabigatran treatment is a more potent anticoagulant than apixaban and rivaroxaban. However, as these results are not supported by clinical data, they are probably more related to the assays used and highlight the difficulty of measuring and comparing the effect of anticoagulants.
直接口服抗凝剂(DOAC)之间存在重要的药理学差异,深入了解它们如何影响接受治疗的患者止血的不同方面是可取的。
使用纤维蛋白网络通透性测定法、浊度法凝血和溶解测定法、校准自动化血栓图(CAT)、凝血酶-抗凝血酶复合物(TAT)和 D-二聚体的血浆水平以及 DOAC 浓度、PT-INR 和 aPTT 分析接受达比加群( = 23)、利伐沙班( = 26)或阿哌沙班( = 20)治疗的患者的血液样本。作为比较,我们还分析了接受华法林治疗的 27 名患者的样本。
与接受利伐沙班和阿哌沙班治疗的患者相比,接受达比加群治疗的患者的纤维蛋白网络更具通透性,CAT 和浊度测定法的滞后时间更长,血浆中 D-二聚体水平更低,且纤维蛋白网络的通透性也高于接受华法林治疗的患者。接受达比加群治疗的患者的凝血溶解时间略长于接受利伐沙班治疗的患者。与接受阿哌沙班治疗的患者相比,接受华法林治疗的患者形成的纤维蛋白网络更具通透性,CAT 测定法的滞后时间更长,且峰值凝血酶和 ETP 低于接受两种 Xa 因子抑制剂治疗的患者。
本研究结果表明,达比加群的治疗效果强于阿哌沙班和利伐沙班。然而,由于这些结果没有得到临床数据的支持,它们可能与所用的检测方法更相关,并突出了测量和比较抗凝剂效果的困难。