Coagulation Disorders Unit, Clinical Chemistry, HUSLAB Laboratory Services, Helsinki University Central Hospital, Helsinki, Finland.
Clin Chem. 2013 May;59(5):807-14. doi: 10.1373/clinchem.2012.198788. Epub 2013 Feb 1.
Laboratory tests to assess novel oral anticoagulants (NOACs) are under evaluation. Routine monitoring is unnecessary, but under special circumstances bioactivity assessment becomes crucial. We analyzed the effects of NOACs on coagulation tests and the availability of specific assays at different laboratories.
Plasma samples spiked with dabigatran (Dabi; 120 and 300 μg/L) or rivaroxaban (Riva; 60, 146, and 305 μg/L) were sent to 115 and 38 European laboratories, respectively. International normalized ratio (INR) and activated partial thromboplastin time (APTT) were analyzed for all samples; thrombin time (TT) was analyzed specifically for Dabi and calibrated anti-activated factor X (anti-Xa) activity for Riva. We compared the results with patient samples.
Results of Dabi samples were reported by 73 laboratories (13 INR and 9 APTT reagents) and Riva samples by 22 laboratories (5 INR and 4 APTT reagents). Both NOACs increased INR values; the increase was modest, albeit larger, for Dabi, with higher CV, especially with Quick (vs Owren) methods. Both NOACs dose-dependently prolonged the APTT. Again, the prolongation and CVs were larger for Dabi. The INR and APTT results varied reagent-dependently (P < 0.005), with less prolongation in patient samples. TT results (Dabi) and calibrated anti-Xa results (Riva) were reported by only 11 and 8 laboratories, respectively.
The screening tests INR and APTT are suboptimal in assessing NOACs, having high reagent dependence and low sensitivity and specificity. They may provide information, if laboratories recognize their limitations. The variation will likely increase and the sensitivity differ in clinical samples. Specific assays measure NOACs accurately; however, few laboratories applied them.
目前正在评估用于评估新型口服抗凝剂（NOAC）的实验室检测方法。常规监测并非必需，但在特殊情况下，生物活性评估至关重要。我们分析了 NOAC 对不同实验室凝血检测的影响和特定检测方法的可用性。
将达比加群（Dabi；120 和 300 μg/L）或利伐沙班（Riva；60、146 和 305 μg/L）的血浆样本分别寄送至 115 和 38 个欧洲实验室。所有样本均分析国际标准化比值（INR）和活化部分凝血活酶时间（APTT）；Dabi 样本专门分析凝血酶时间（TT），Riva 样本分析校准抗活化因子 X（anti-Xa）活性。我们将结果与患者样本进行了比较。
73 个实验室（13 个 INR 和 9 个 APTT 试剂）报告了 Dabi 样本的结果，22 个实验室（5 个 INR 和 4 个 APTT 试剂）报告了 Riva 样本的结果。两种 NOAC 均增加了 INR 值；Dabi 的增加幅度适中，但更大，CV 更高，尤其是使用快速（vs. Owren）方法时。两种 NOAC 均剂量依赖性地延长了 APTT。同样，Dabi 的延长和 CV 更大。INR 和 APTT 结果因试剂而异（P < 0.005），患者样本的延长程度较低。仅 11 个和 8 个实验室分别报告了 TT 结果（Dabi）和校准抗 Xa 结果（Riva）。
筛查试验 INR 和 APTT 在评估 NOAC 方面并不理想，具有高度的试剂依赖性和低灵敏度和特异性。如果实验室认识到其局限性，它们可能会提供信息。在临床样本中，这种差异可能会增加，灵敏度也会不同。特定检测方法可以准确测量 NOAC；然而，很少有实验室应用它们。
