Slavik Ludek, Lukes Jiri, Friedecky David, Zhanelova Monika, Nemcova Marketa, Ulehlova Jana, Prochazkova Jana, Hlusi Antonin, Palova Miroslava, Vaclavik Jan
Clin Lab. 2018 Oct 1;64(10):1611-1621. doi: 10.7754/Clin.Lab.2018.180335.
Detection of new oral anticoagulant (NOAC) levels by screening, special and global tests, and liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) is important in clinical situations when the cause of bleeding needs to be determined.
We compared a routine coagulation test, special function test for NOACs, global coagulation test, and an LC-MS/MS method that enables simultaneous determination of apixaban, dabigatran and rivaroxaban in human plasma within one analysis to determine the optimal indication of the comparison methods, including their limitations and interferences.
This study was conducted on a set of blood samples from 116 patients treated with NOACs. The results of both specific dilute thrombin time (dTT) tests for dabigatran provided the same results as the activated partial thromboplastin time (aPTT) screening test in comparison with LC-MS/MS as a reference. The dTT assay HemosIL® showed better results for low concentrations when compared to LC-MS/MS than dTT HYPHEN® as HemosIL® uses a non-linear calibration curve. Results of the specific anti-Xa assay yielded better results than the prothrombin time test in comparison with LC-MS/MS as a reference, especially for apixaban, but also for rivaroxaban. Our LC MS/MS method is simply feasible, but only in a specialized laboratory. The method is easy-to-use for the simultaneous determination of all dabigatran, apixaban and rivaroxaban by LC-MS/MS within three minutes with a concentration range of 1 to 500 µg/L without dilution.
In the normal practice of the coagulation laboratory, it is advisable to use specific tests for NOAC determination as screening and global assays are not sufficiently specific. The dTT test is the optimal choice for dabigatran determination and for xabans to determine anti-Xa activity. The LC-MS/MS method is suitable as an arbitration method for serious conditions.
在需要确定出血原因的临床情况下，通过筛查、特殊和全面检测以及液相色谱 - 串联质谱法（LC-MS/MS）检测新型口服抗凝剂（NOAC）水平非常重要。
我们比较了常规凝血试验、NOACs特殊功能试验、全面凝血试验以及一种LC-MS/MS方法，该方法能够在一次分析中同时测定人血浆中的阿哌沙班、达比加群和利伐沙班，以确定比较方法的最佳适用情况，包括其局限性和干扰因素。
本研究对116例接受NOAC治疗的患者的一组血液样本进行。与作为参考的LC-MS/MS相比，达比加群的两种特定稀释凝血酶时间（dTT）试验结果与活化部分凝血活酶时间（aPTT）筛查试验结果相同。与LC-MS/MS相比，dTT检测试剂HemosIL®在低浓度时比dTT HYPHEN®表现更好，因为HemosIL®使用非线性校准曲线。与作为参考的LC-MS/MS相比，特定抗Xa试验的结果比凝血酶原时间试验更好，特别是对于阿哌沙班，对利伐沙班也是如此。我们的LC-MS/MS方法简单可行，但仅适用于专业实验室。该方法易于使用，可在三分钟内通过LC-MS/MS同时测定所有达比加群、阿哌沙班和利伐沙班，浓度范围为1至500μg/L，无需稀释。
在凝血实验室的常规操作中，建议使用特定试验来测定NOAC，因为筛查和全面检测的特异性不足。dTT试验是测定达比加群以及测定Xa因子抑制剂抗Xa活性的最佳选择。LC-MS/MS方法适合作为严重情况的仲裁方法。
