直接口服抗凝剂治疗期间的紧急凝血评估：局限性与解决方案
Emergency Coagulation Assessment During Treatment With Direct Oral Anticoagulants: Limitations and Solutions.
作者信息
Ebner Matthias, Birschmann Ingvild, Peter Andreas, Härtig Florian, Spencer Charlotte, Kuhn Joachim, Blumenstock Gunnar, Zuern Christine S, Ziemann Ulf, Poli Sven
机构信息
From the Department of Internal Medicine and Cardiology, Charité University Medicine Berlin-Campus Virchow Klinikum, Germany (M.E.); Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center, Bad Oeynhausen, Ruhr University, Bochum, Germany (I.B., J.K.); Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research (M.E., F.H., C.S., U.Z., S.P.), Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry of the Department of Internal Medicine, German Center for Diabetes Research, and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich (A.P.), Department of Cardiology and Cardiovascular Medicine (C.S.Z.), and Department of Clinical Epidemiology and Applied Biometry (G.B.) at the University of Tübingen, Germany.
出版信息
Stroke. 2017 Sep;48(9):2457-2463. doi: 10.1161/STROKEAHA.117.017981. Epub 2017 Aug 3.
BACKGROUND AND PURPOSE
In patients receiving direct oral anticoagulants (DOACs), emergency treatment like thrombolysis for acute ischemic stroke is complicated by insufficient availability of DOAC-specific coagulation tests. Conflicting recommendations have been published concerning the use of global coagulation assays for ruling out relevant DOAC-induced anticoagulation.
METHODS
Four hundred eighty-one samples from 96 DOAC-treated patients were tested using prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT), DOAC-specific assays (anti-Xa activity, diluted TT), and liquid chromatography-tandem mass spectrometry. Sensitivity and specificity of test results to identify DOAC concentrations <30 ng/mL were calculated. Receiver operating characteristic analyses were used to define reagent-specific cutoff values.
RESULTS
Normal PT and aPTT provide insufficient specificity to safely identify DOAC concentrations <30 ng/mL (rivaroxaban/PT: specificity, 77%/sensitivity, 94%; apixaban/PT: specificity, 13%/sensitivity, 94%, dabigatran/aPTT: specificity, 49%/sensitivity, 91%). Normal TT was 100% specific for dabigatran, but sensitivity was 26%. In contrast, reagent-specific PT and aPTT cutoffs provided >95% specificity and a specific TT cutoff enhanced sensitivity for dabigatran to 84%. For apixaban, no cutoffs could be established.
CONCLUSIONS
Even if highly DOAC-reactive reagents are used, normal results of global coagulation tests are not suited to guide emergency treatment: whereas normal PT and aPTT lack specificity to rule out DOAC-induced anticoagulation, the low sensitivity of normal TT excludes the majority of eligible patients from treatment. However, reagent-specific cutoffs for global coagulation tests ensure high specificity and optimize sensitivity for safe emergency decision making in rivaroxaban- and dabigatran-treated patients.
CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02371044 and NCT02371070.
背景与目的
在接受直接口服抗凝剂（DOACs）治疗的患者中，急性缺血性卒中的溶栓等紧急治疗因缺乏DOAC特异性凝血检测而变得复杂。关于使用全血凝固试验排除相关DOAC诱导的抗凝作用，已发表了相互矛盾的建议。
方法
使用凝血酶原时间（PT）、活化部分凝血活酶时间（aPTT）和凝血酶时间（TT）、DOAC特异性检测（抗Xa活性、稀释TT）以及液相色谱-串联质谱法对96例接受DOAC治疗患者的481份样本进行检测。计算检测结果识别DOAC浓度<30 ng/mL的敏感性和特异性。采用受试者工作特征分析来确定试剂特异性临界值。
结果
正常PT和aPTT提供的特异性不足，无法安全识别DOAC浓度<30 ng/mL（利伐沙班/PT：特异性77%/敏感性94%；阿哌沙班/PT：特异性13%/敏感性94%，达比加群/aPTT：特异性49%/敏感性91%）。正常TT对达比加群具有100%的特异性，但敏感性为26%。相比之下，试剂特异性PT和aPTT临界值提供了>95%的特异性，而特异性TT临界值将达比加群的敏感性提高到84%。对于阿哌沙班，无法确定临界值。
结论
即使使用高度DOAC反应性试剂，全血凝固试验的正常结果也不适合指导紧急治疗：正常PT和aPTT缺乏排除DOAC诱导抗凝作用的特异性，而正常TT的低敏感性将大多数符合条件的患者排除在治疗之外。然而，全血凝固试验的试剂特异性临界值可确保高特异性，并优化对接受利伐沙班和达比加群治疗患者进行安全紧急决策的敏感性。
临床试验注册
网址：http://www.clinicaltrials.gov。唯一标识符：NCT02371044和NCT02371070。
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