Laboratory assessment of novel oral anticoagulants: method suitability and variability between coagulation laboratories.

BACKGROUND 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. METHODS 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 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. CONCLUSIONS 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.