Bliden Kevin P, Chaudhary Rahul, Mohammed Nafees, Muresan Adina A, Lopez-Espina Carlos G, Cohen Eli, Raviv Gabriel, Doubleday Marc, Zaman Fowzia, Mathew Blessy, Tantry Udaya S, Gurbel Paul A
Interventional Cardiology and Cardiovascular Medicine Research, Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, 3300 Gallows Road, Falls Church, VA, USA.
Haemonetics Corporation, Braintree, MA, USA.
J Thromb Thrombolysis. 2017 May;43(4):437-445. doi: 10.1007/s11239-017-1477-1.
Non vitamin K oral anticoagulants (NOACs) do not require regular monitoring but information about their pharmacodynamic effect may be importantin situations like trauma, stroke oremergent surgery. Currently, no standardized point-of-care test is available to evaluate the anticoagulant effects of NOACs. We evaluated the anticoagulant effect of NOACs with the next generation point-of-care TEG assay (TEG® 6S) based on a fully-automated thrombelastography system. We used two TEG® 6S assays, the DTI assay and Anti-Factor Xa (AFXa) assay, to detect anticoagulant effects and classify NOACs. Blood from healthy volunteers (n = 26) was used to obtain a baseline reference range. Data derived from patients on factor Xa inhibitors (FXi) (rivaroxaban and apixaban) (n = 39), and direct thrombin inhibitors (DTIs) (dabigatran) (n = 25) were compared against the reference range for detection of drug effect and drug classification. TEG®6s R-time highly correlated to each NOAC. Presence of NOACs caused elongation of R-time on the AFXa assay compared to the reference range (4.3 ± 1.7 vs. 1.3 ± 0.3 min. for FXi, p < 0.001 and 3.5 ± 1.2 vs. 1.3 ± 0.3 min. for DTI, p < 0.001). R-time on the DTI assay was elongated only in presence of a DTI (3.4 ± 1.0 vs. 1.5 ± 0.2 min, p < 0.001). The cutoff for detection of a DTI effect was an R time of 1.9 min and for anti-Xa effect was 1.95 min. For detection of NOAC therapy, there was ≥92% sensitivity and ≥95% specificity. The automated TEG®6s NOAC assay may be an effective tool to identify an anticoagulant effect from NOAC therapy and facilitate care of patients with bleeding or at risk of bleeding in the event of needing emergency surgery.
非维生素K口服抗凝药(NOACs)不需要定期监测,但在创伤、中风或急诊手术等情况下,有关其药效学作用的信息可能很重要。目前,尚无标准化的即时检验可用于评估NOACs的抗凝效果。我们基于全自动血栓弹力图系统,采用新一代即时检验血栓弹力图检测法(TEG® 6S)评估了NOACs的抗凝效果。我们使用两种TEG® 6S检测法,即稀释凝血酶时间(DTI)检测法和抗Xa因子(AFXa)检测法,来检测抗凝效果并对NOACs进行分类。利用健康志愿者(n = 26)的血液获得基线参考范围。将来自服用Xa因子抑制剂(FXi)(利伐沙班和阿哌沙班)(n = 39)以及直接凝血酶抑制剂(DTIs)(达比加群)(n = 25)的患者的数据与参考范围进行比较,以检测药物效果和进行药物分类。TEG®6s的反应时间(R-time)与每种NOAC高度相关。与参考范围相比,在AFXa检测法中,NOACs的存在导致R-time延长(FXi组为4.3±1.7分钟对1.3±0.3分钟,p<0.001;DTI组为3.5±1.2分钟对1.3±0.3分钟,p<0.001)。仅在存在DTI的情况下,DTI检测法的R-time才会延长(3.4±1.0分钟对1.5±0.2分钟,p<0.001)。检测DTI效果的临界值为R时间1.9分钟,检测抗Xa效果的临界值为1.95分钟。对于检测NOAC治疗,灵敏度≥92%,特异性≥95%。自动化的TEG®6s NOAC检测法可能是一种有效的工具,可用于识别NOAC治疗的抗凝效果,并在需要急诊手术时,为出血或有出血风险的患者提供便利的护理。