Groene Philipp, Butte Jennifer, Thaler Sarah, Görlinger Klaus, Schäfer Simon T
Department of Anaesthesiology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany.
TEM Innovations GmbH, Munich, Germany.
Thromb J. 2022 Jul 21;20(1):40. doi: 10.1186/s12959-022-00400-3.
The detection of direct oral anticoagulants (DOACs) is still challenging but important in emergency patients. We recently demonstrated that modified thromboelastometry can detect rivaroxaban and dabigatran. Data on the detection rates of modified compared to standard thromboelastometric tests of apixaban and edoxaban, are missing. The aim of this in-vitro dose-effect-study was to add data on these DOACs and to evaluate thromboelastometric tests in-vitro using data of both studies.
The study was approved by the Ludwig-Maximilians-University ethics committee (No 17-525-2). Written informed consent was obtained from all individuals. Blood samples of healthy volunteers and samples of 10 volunteers for each DOAC were used. Blood samples were spiked with six different concentrations of edoxaban and apixaban (0ng/ml; 31.25ng/ml; 62.5ng/ml; 125ng/ml; 250 ng/ml; 500ng/ml). Modified tests (low-tissue-factor test TFTEM and ecarin-based test ECATEM) as well as standard tests (e.g. FIBTEM) analyzing extrinsic pathway of coagulation were used. Receiver operating characteristics analyzes were performed as well as regression analyzes.
TFTEM CT correlated well with anti-Xa levels of apixaban and edoxaban (apixaban: r = 0.8064 p < 0.0001; edoxaban: r = 0.8603; p < 0.0001). The detection of direct FXa inhibitors (> 30 ng/mL) was successful with FIBTEM CT with a sensitivity and specificity of 81% and 90%, respectively. As expected, ECATEM CT was not prolonged by direct FXa-inhibitors due to its specificity for direct thrombin inhibitors. Again, TFTEM CT provided the highest sensitivity and specificity for the detection of direct FXa inhibitors with 96% and 95%, respectively. ECATEM test showed 100% sensitivity and 100% specificity for the detection of dabigatran.
Our study presents modified thromboelastometric tests with improved detection of even low DOAC concentrations > 30 ng/mL, including apixaban in-vitro. The study thus complements the previously published data on dabigatran and rivaroxaban. Validation studies must confirm the results due to the explanatory design of this study.
在急诊患者中，直接口服抗凝剂（DOACs）的检测仍然具有挑战性，但却很重要。我们最近证明，改良血栓弹力图法可以检测利伐沙班和达比加群。关于阿哌沙班和依度沙班改良血栓弹力图检测与标准检测的检出率数据尚缺。这项体外剂量效应研究的目的是补充这些DOACs的数据，并利用两项研究的数据在体外评估血栓弹力图检测。
该研究经路德维希 - 马克西米利安大学伦理委员会批准（编号17 - 525 - 2）。所有个体均获得书面知情同意。使用健康志愿者的血样以及每种DOAC的10名志愿者的样本。血样中加入六种不同浓度的依度沙班和阿哌沙班（0ng/ml；31.25ng/ml；62.5ng/ml；125ng/ml；250 ng/ml；500ng/ml）。采用改良检测方法（低组织因子检测TFTEM和基于蛇毒凝血酶的检测ECATEM）以及分析凝血外源性途径的标准检测方法（如FIBTEM）。进行了受试者工作特征分析以及回归分析。
TFTEM的凝血时间（CT）与阿哌沙班和依度沙班的抗Xa水平相关性良好（阿哌沙班：r = 0.8064，p < 0.0001；依度沙班：r = 0.8603；p < 0.0001）。FIBTEM的CT对直接FXa抑制剂（> 30 ng/mL）的检测成功，敏感性和特异性分别为81%和90%。正如预期的那样，由于ECATEM对直接凝血酶抑制剂的特异性，直接FXa抑制剂不会延长ECATEM的CT。同样，TFTEM的CT对直接FXa抑制剂检测的敏感性和特异性最高，分别为96%和95%。ECATEM检测对达比加群的检测显示出100%的敏感性和100%的特异性。
我们的研究提出了改良血栓弹力图检测方法，即使对于低至> 30 ng/mL的DOAC浓度，包括体外阿哌沙班，其检测效果也有所改善。因此，该研究补充了先前发表的关于达比加群和利伐沙班的数据。由于本研究的解释性设计，验证研究必须证实这些结果。
