Peter Quehenberger, Medical University of Vienna, Department of Laboratory Medicine, Waehringer Guertel 18-20, 1090 Vienna, Austria, Tel.: +43 1 40400 53830, Fax: +43 1 40400 53920, E-mail:
Thromb Haemost. 2016 Aug 1;116(2):235-40. doi: 10.1160/TH16-02-0081. Epub 2016 Apr 14.
Non-vitamin K antagonist oral anticoagulants (NOAC), including rivaroxaban, apixaban or dabigatran, regularly show relevant effects on coagulation tests, making the interpretation of results difficult. The aim of this study was to evaluate possible interferences of NOACs in trough level concentrations in lupus anticoagulant (LA) testing. Citrate plasma specimens of 30 healthy volunteers were spiked with rivaroxaban, apixaban or dabigatran in four plasma concentration levels at or below trough NOAC levels. The NOAC concentration was measured using dedicated surrogate concentration tests and a stepwise diagnostic procedure for LA-testing was applied using screening, mixing and confirmatory testing. Results were compared to NOAC-free specimens. Starting with a plasma concentration of 12.5 ng/ml, dabigatran-spiked specimens showed significant prolongations in the lupus anticoagulant-sensitive activated partial thromboplastin time (aPTT-LA) as well as in the Dilute Russell viper venom time (dRVVT), leading to 43.3 % false positives in confirmatory testing in the dRVVT. In contrast, rivaroxaban, beginning with 7.5 ng/ml, exclusively affected dRVVT-based tests. In confirmatory tests, 30.0 % of rivaroxaban-spiked specimens showed false positive results. Starting with 18.75 ng/ml apixaban, a significant prolongation of the dRVVT and up to 20.7 % false positives in confirmatory tests were found. In contrast to other NOACs tested, apixaban did not present with a dose-dependent increase of the dRVVT ratio. In conclusion, the rate of false positive results in LA-testing is unacceptably high at expected trough levels of NOACs. Even at plasma concentrations below the LLOQ of commercially available surrogate tests, LA testing is best avoided in patients with NOAC therapy.
非维生素 K 拮抗剂口服抗凝剂（NOAC），包括利伐沙班、阿哌沙班或达比加群，经常对凝血试验产生相关影响，使得结果解释变得困难。本研究旨在评估 NOAC 在狼疮抗凝剂（LA）检测中的谷浓度水平可能产生的干扰。用四种血浆浓度水平（低于或等于 NOAC 的谷浓度水平）在 30 名健康志愿者的枸橼酸盐血浆标本中加入利伐沙班、阿哌沙班或达比加群。使用专用替代浓度试验测量 NOAC 浓度，并应用 LA 试验的逐步诊断程序进行筛选、混合和确认试验。结果与无 NOAC 的标本进行比较。从 12.5ng/ml 的血浆浓度开始，达比加群加标标本的狼疮抗凝剂敏感的活化部分凝血活酶时间（aPTT-LA）以及稀释蝰蛇毒时间（dRVVT）显著延长，导致在 dRVVT 的确认试验中出现 43.3%的假阳性。相比之下，利伐沙班从 7.5ng/ml 开始，仅影响基于 dRVVT 的试验。在确认试验中，30.0%的利伐沙班加标标本出现假阳性结果。从 18.75ng/ml 的阿哌沙班开始，dRVVT 显著延长，在确认试验中高达 20.7%的假阳性。与其他测试的 NOAC 不同，阿哌沙班的 dRVVT 比值没有剂量依赖性增加。总之，在预期的 NOAC 谷浓度水平下，LA 试验中假阳性结果的比例高得令人无法接受。即使在商业上可用的替代试验的LLOQ 以下的血浆浓度下，也最好避免在接受 NOAC 治疗的患者中进行 LA 试验。
