Department of Clinical Sciences, Division of Cardiovascular Medicine, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
Department of Laboratory Medicine, Division of Clinical Immunology and Transfusion Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
J Thromb Haemost. 2018 Dec;16(12):2462-2470. doi: 10.1111/jth.14308. Epub 2018 Nov 1.
Essentials A rapid test to detect thrombin inhibition by dabigatran would be valuable in acute situations. A thrombin-based trigger was applied in whole blood using rotation thromboelastometry. Effects of dabigatran were assessed in vitro and in samples from patients on dabigatran. The test produced data rapidly and was sensitive to dabigatran concentrations from 20 to 500 ng mL . SUMMARY: Background Rapid determination of the anticoagulant effect of dabigatran is essential in emergency situations. Objective To study a viscoelastic test (rotational thromboelastometry [ROTEM]) for rapid determination of dabigatran effects in whole blood samples. Method ROTEM measurements were performed with comparison of two triggers (thrombin-based versus the commercial tissue factor-based trigger Ex-tem) in samples from 10 healthy donors spiked with dabigatran (20-500 ng mL ) and in samples from 35 patients receiving dabigatran treatment; 10 healthy subjects served as controls. Clotting time (CT) and the difference in CT without versus with addition of the dabigatran antidote idarucizumab (CT ) were measured. Addition of idarucizumab reveals the contribution of dabigatran to ROTEM measurements and its potential reversibility. Results In vitro studies showed that thrombin CT and thrombin CT were more sensitive than Ex-tem CT and Ex-tem CT in detecting dabigatran in whole blood samples. In patient samples, when thrombin CT and thrombin CT were used, it was possible to detect dabigatran with a cut-off of dabigatran at 20 ng mL , whereas, when Ex-tem CT and Ex-tem CT were used, the method was less sensitive. Data from patient samples were obtained within 15 min of blood sampling. Conclusions ROTEM CT with a thrombin-based trigger is more sensitive to dabigatran effects than Ex-tem CT, and detects anticoagulant effects of drug concentrations in the low-very low therapeutic range. Analysis with idarucizumab (CT ) reveals dabigatran-specific effects. As data are rapidly obtained, this method could, with further development and validation of its performance, be suitable for detecting clinically significant dabigatran effects in emergency situations.
Essentials 在急性情况下，检测达比加群抑制凝血酶的快速检测方法将具有重要价值。使用旋转血栓弹性测定法在全血中应用基于凝血酶的触发。在体外和接受达比加群治疗的患者样本中评估达比加群的作用。该检测方法快速产生数据，对 20 至 500ng/ml 的达比加群浓度敏感。
背景 在紧急情况下，快速确定达比加群的抗凝效果至关重要。目的 研究一种粘弹性检测方法（旋转血栓弹性测定法[ROTEM]），用于快速测定全血样本中达比加群的作用。方法 在 10 名健康供体样本中，用两种触发物（基于凝血酶与商业组织因子触发物 Ex-tem）进行 ROTEM 测量，并与接受达比加群治疗的 35 名患者样本进行比较；10 名健康受试者作为对照。测量凝血时间（CT）和加入达比加群拮抗剂依达鲁单抗后 CT 的差异（CT）。加入依达鲁单抗可揭示达比加群对 ROTEM 测量的贡献及其潜在的可逆性。结果 体外研究表明，在全血样本中，凝血酶 CT 和凝血酶 CT 比 Ex-tem CT 和 Ex-tem CT 更敏感地检测达比加群。在患者样本中，当使用凝血酶 CT 和凝血酶 CT 时，当使用达比加群 20ng/ml 时，可检测到达比加群，而当使用 Ex-tem CT 和 Ex-tem CT 时，该方法的灵敏度较低。从患者样本中获得的数据在采血后 15 分钟内获得。结论 基于凝血酶的 ROTEM CT 比 Ex-tem CT 对达比加群的作用更敏感，并检测到药物浓度在低至超低治疗范围内的抗凝作用。使用依达鲁单抗（CT）进行分析可揭示达比加群的特异性作用。由于数据快速获得，因此该方法在进一步开发和验证其性能后，可用于检测紧急情况下临床意义上的达比加群作用。
