Artang Ramin, Anderson Maren, Nielsen Jorn D
Essentia Health St. Mary's Heart and Vascular Center Duluth Minnesota.
Bispebjerg University Hospital University of Copenhagen Kobenhavn Denmark.
Res Pract Thromb Haemost. 2019 May 12;3(3):391-396. doi: 10.1002/rth2.12206. eCollection 2019 Jul.
The ability to assess the hemostatic effect of the direct oral anticoagulant (DOACs) may be valuable in clinical situations such as bleeding or thrombosis, before urgent surgery, or reversal of anticoagulation. We sought to assess the anticoagulant effect of DOACs with the new-generation fully automated thrombelastograph TEG 6s using resonance-frequency viscoelasticity measurements and disposable multichannel microfluidic cartridges.
A single dose of oral dabigatran 150 mg, rivaroxaban 20 mg, or apixaban 5 mg was given to 9 healthy males. Phlebotomy was performed at 0, 1, and 3 hours after administration of DOAC. TEG parameters were measured using TEG 6s. Concentrations of DOACs were measured using chromogenic assays. The TEG parameters were correlated to the DOAC concentrations.
The reaction time (R) demonstrated the strongest response to DOAC intake. There were no correlations between other TEG parameters and DOAC concentrations. Using the direct thrombin inhibitor (DTI) channel, R was significantly correlated with dabigatran levels (=0.94, <0.0001). Using the anti-factor Xa (AFXa) channel, R was significantly correlated with rivaroxaban and apixaban levels (=0.93 and =0.83, respectively; <0.0001 for both). R >2.5 minutes for dabigatran (DTI channel), >2.5 minutes for apixaban, and >1.8 minutes for rivaroxaban (AFXa channel) were associated with 100% sensitivity and ≥ 90% specificity to detect DOAC levels of ≥ 50 ng/mL.
We have demonstrated that TEG 6s R has significant correlation with DOAC blood concentrations and has potential for monitoring the DOAC's effect on hemostasis with reasonable sensitivity in the small sample analyzed. This novel technology is easy to use on a small volume of whole blood without requiring a specialized laboratory. Further study is warranted to correlate R with clinical outcomes.
在出血或血栓形成等临床情况、紧急手术前或抗凝逆转时，评估直接口服抗凝剂（DOACs）的止血效果可能具有重要价值。我们试图使用新一代全自动血栓弹力图仪TEG 6s，通过共振频率粘弹性测量和一次性多通道微流控芯片来评估DOACs的抗凝效果。
给予9名健康男性单剂量口服达比加群150mg、利伐沙班20mg或阿哌沙班5mg。在给予DOAC后0、1和3小时进行静脉采血。使用TEG 6s测量TEG参数。使用显色测定法测量DOACs的浓度。将TEG参数与DOAC浓度进行相关性分析。
反应时间（R）对DOAC摄入的反应最强。其他TEG参数与DOAC浓度之间无相关性。使用直接凝血酶抑制剂（DTI）通道时，R与达比加群水平显著相关（=0.94，<0.0001）。使用抗Xa因子（AFXa）通道时，R与利伐沙班和阿哌沙班水平显著相关（分别为=0.93和=0.83；两者均<0.0001）。达比加群（DTI通道）的R>2.5分钟、阿哌沙班的R>2.5分钟以及利伐沙班（AFXa通道）的R>1.8分钟与检测DOAC水平≥50ng/mL的100%敏感性和≥90%特异性相关。
我们已经证明，TEG 6s的R与DOAC血液浓度具有显著相关性，并且在分析的小样本中具有以合理敏感性监测DOAC对止血作用的潜力。这项新技术易于在少量全血上使用，无需专门实验室。有必要进一步研究将R与临床结果相关联。
