1 Department of Internal Medicine and Cardiology Charité University Medicine Berlin Campus Virchow Klinikum Berlin Germany.
2 Department of Neurology with Focus on Neurovascular Diseases and Neurooncology and Hertie Institute for Clinical Brain Research University Hospital Tübingen Germany.
J Am Heart Assoc. 2018 Oct 2;7(19):e009807. doi: 10.1161/JAHA.118.009807.
Background During treatment with direct oral anticoagulants ( DOAC ), coagulation assessment is required before thrombolysis, surgery, and if anticoagulation reversal is evaluated. Limited data support the accuracy of DOAC -specific coagulation assays around the current safe-for-treatment threshold of 30 ng/ mL . Methods and Results In 481 samples obtained from 96 patients enrolled at a single center, DOAC concentrations were measured using Hemoclot direct thrombin inhibitor assay, Biophen direct thrombin inhibitor assay or ecarin clotting time for dabigatran, chromogenic anti-Xa assay ( AXA ) for factor Xa inhibitors (rivaroxaban, apixaban) and ultraperformance liquid chromatography-tandem mass spectrometry as reference. All dabigatran-specific assays had high sensitivity to concentrations >30 ng/ mL , but specificity was lower for Hemoclot direct thrombin inhibitor assay (78.2%) than for Biophen direct thrombin inhibitor assay (98.9%) and ecarin clotting time (94.6%). AXA provided high sensitivity and specificity for rivaroxaban, but low sensitivity for apixaban (73.8%; concentrations up to 82 ng/ mL were misclassified as <30 ng/ mL ). If no DOAC -specific calibration for AXA is available, results 2-fold above the upper limit of normal indicate relevant rivaroxaban concentrations. For apixaban, all elevated results should raise suspicion of relevant anticoagulation. Conclusions DOAC -specific tests differ considerably in diagnostic performance for concentrations close to the currently accepted safe-for-treatment threshold. Compared with Biophen direct thrombin inhibitor assay and ecarin clotting time, limited specificity of Hemoclot direct thrombin inhibitor assay poses a high risk of unnecessary anticoagulation reversal or treatment delays in patients on dabigatran. While AXA accurately detected rivaroxaban, the impact of low apixaban levels on the assay was weak. Hence, AXA results need to be interpreted with extreme caution when used to assess hemostatic function in patients on apixaban. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 02371044, NCT 02371070.
在使用直接口服抗凝剂（DOAC）治疗期间，在溶栓、手术前以及评估抗凝逆转时需要进行凝血评估。目前在 30ng/ml 的安全治疗阈值左右，支持 DOAC 特异性凝血检测的准确性的数据有限。
在单一中心入组的 96 名患者的 481 个样本中，使用 Hemoclot 直接凝血酶抑制剂测定法、Biophen 直接凝血酶抑制剂测定法或蝰蛇凝血时间测定法检测达比加群的 DOAC 浓度，发色底物抗-Xa 测定法（AXA）检测因子 Xa 抑制剂（利伐沙班、阿哌沙班），超高效液相色谱-串联质谱法作为参考。所有达比加群特异性检测法对浓度>30ng/ml 均具有高灵敏度，但与 Biophen 直接凝血酶抑制剂测定法（98.9%）和蝰蛇凝血时间（94.6%）相比，Hemoclot 直接凝血酶抑制剂测定法的特异性较低（78.2%）。AXA 对利伐沙班具有高灵敏度和特异性，但对阿哌沙班的灵敏度较低（73.8%；浓度高达 82ng/ml 的样本被错误分类为<30ng/ml）。如果没有 AXA 的 DOAC 特异性校准，则结果高出正常上限 2 倍表明存在相关的利伐沙班浓度。对于阿哌沙班，所有升高的结果都应怀疑存在相关抗凝作用。
在接近当前接受的安全治疗阈值时，针对浓度接近当前接受的安全治疗阈值的 DOAC 特异性检测法在诊断性能上存在显著差异。与 Biophen 直接凝血酶抑制剂测定法和蝰蛇凝血时间相比，Hemoclot 直接凝血酶抑制剂测定法特异性有限，这会使达比加群治疗患者面临不必要的抗凝逆转或治疗延迟的高风险。虽然 AXA 能准确检测到利伐沙班，但低浓度的阿哌沙班对该检测法的影响较弱。因此，在使用 AXA 评估阿哌沙班患者的止血功能时，需要极其谨慎地解释结果。
https://www.clinicaltrials.gov。唯一标识符：NCT 02371044，NCT 02371070。
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