Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy.
IRCCS Cà Granda Maggiore Hospital Foundation, Milan, Italy.
J Thromb Haemost. 2018 Mar;16(3):565-570. doi: 10.1111/jth.13949. Epub 2018 Jan 29.
Essentials Tests for direct oral anticoagulants (DOACs) are not widely applied. These tests are perceived to be difficult to run and subjected to large between-lab variation. We carried out proficiency testing surveys for DOAC testing in Italy. Interlab variability was small and similar to that of the international normalised ratio.
Background Tests for direct oral anticoagulants (DOACs) are not widely available. The perception that they are difficult to perform and are subject to large between-laboratory variation makes their implementation difficult. Aims We carried out proficiency-testing surveys for DOACs within the activity of the external quality-assessment scheme of the Italian Federation of Thrombosis Centers. Design Participants were provided with coded freeze-dried plasmas without or with graded concentrations of the three main DOACs, and asked to measure prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time and DOAC concentrations with dedicated tests. The results were centralized for statistical analysis. Results and conclusions All participants (n = 235) reported results for PT and APTT, and approximately one-third reported results for DOAC concentration. PT and APTT showed variable responsiveness to DOACs: PT was more responsive to rivaroxaban than to dabigatran or apixaban. APTT was more responsive to dabigatran than to rivaroxaban or apixaban. The thrombin time ratio (test/normal) was close to unity for plasmas without dabigatran, and was high (i.e. 7.6-fold or 15.4-fold longer than the plasma free from the drug) for plasmas containing dabigatran at low (i.e. 42 ng mL ) or high (i.e. 182 ng mL ) concentration. Dedicated tests were responsive to the respective drugs, and their interlaboratory variability was relatively small (overall coefficients of variation of 8.7%, 8.4% or 10.3% for dabigatran, rivaroxaban and apixaban, respectively) and was comparable to that observed within the same survey for the International Normalized Ratio (i.e. 11.4%). In conclusion, tests for DOAC measurement performed reasonably well in a national quality-control scheme. Regulatory authorities should urgently issue recommendations on their use, and clinical laboratories should make them available.
直接口服抗凝剂（DOACs）的基础检测并未广泛应用。这些检测被认为难以实施，并且存在较大的实验室间差异。我们在意大利开展了 DOAC 检测的能力验证调查。实验室间的变异性很小，与国际标准化比值相似。
背景：直接口服抗凝剂（DOACs）的检测并未广泛应用。由于其操作困难，且存在较大的实验室间差异，因此难以实施。目的：我们在意大利血栓形成中心联合会的外部质量评估计划的活动中开展了 DOAC 的能力验证调查。设计：参与者收到了无或分级浓度的三种主要 DOAC 的冻干血浆，并要求使用专用检测方法测量凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间和 DOAC 浓度。结果汇总进行统计分析。结果和结论：所有参与者（n=235）报告了 PT 和 APTT 的结果，约三分之一的参与者报告了 DOAC 浓度的结果。PT 和 APTT 对 DOAC 的反应不同：PT 对利伐沙班的反应比对达比加群或阿哌沙班更敏感。APTT 对达比加群的反应比对利伐沙班或阿哌沙班更敏感。无达比加群的血浆的凝血酶时间比值（测试/正常）接近 1，而含低浓度（即 42ng/mL）或高浓度（即 182ng/mL）达比加群的血浆的比值（即 7.6 倍或 15.4 倍）较高。专用检测方法对各自的药物有反应，其实验室间的变异性相对较小（达比加群、利伐沙班和阿哌沙班的总体变异系数分别为 8.7%、8.4%和 10.3%），与同一调查中观察到的国际标准化比值（即 11.4%）相似。结论：在国家质量控制计划中，DOAC 检测的检测方法表现良好。监管机构应紧急发布关于其使用的建议，临床实验室应提供这些检测方法。
