Determination of the cut-off prothrombin time to estimate plasma rivaroxaban overdose status

Abstract

Laboratory monitoring of rivaroxaban (RIV) is required under certain conditions. Mass spectrometry and anti-factor Xa assays are the recommended methods, which may not be readily available. Prothrombin time (PT) is the most widely used and simple coagulation assay. To set the cutoff PT and international normalized ratio (INR) to estimate RIV overdose status. RIV-spiked pooled normal plasma was used. PT test was performed using a CA-7000 coagulometer and Thromborel S reagent. The precise measurement of RIV concentration at the cut-off PT was evaluated according to the Clinical and Laboratory Standard Institute (CLSI) EP12-A2 guideline. The RIV concentration at 275 ng/mL was analyzed using 40 replicates. Receiver operating characteristic (ROC) analysis was performed to determine the cutoff value for the determination of RIV potential overdose status. An imprecision estimation of PT was conducted with 220.00 ng/mL, 247.50 ng/mL, 261.25 ng/mL, 288.75 ng/mL, 302.50 ng/mL and 330.00 ng/mL concentrations of RIV in 60 replicates. According to the ROC analysis, the cutoff clotting times and INR values to determine the overdose status of RIV were 13.45 s and 1.39. With these values, there was a 92.6% probability that plasma samples with RIV concentration <= 247.50 ng/mL yielded consistently negative (on-therapy dose) results, and those with >= 302.50 ng/mL yield consistent positive (potential overdose) results using our PT assay. PT with a reliable cutoff clotting time and INR can be used to determine the potential overdose status of RIV to facilitate the diagnosis and treatment by controlling the dose.