Real-time detection and differentiation of direct oral anticoagulants (rivaroxaban and dabigatran) using modified thromboelastometric reagents.

INTRODUCTION:Timely measurement of direct oral anticoagulants (DOACs) is challenging, though clinically important. We tested the hypotheses, that thromboelastometry is able to detect dabigatran and rivaroxaban and discriminates between dabigatran and rivaroxaban as representatives of the two groups of DOACs. METHODS AND MATERIALS:We conducted a prospective-observational study: In-vitro dose-effect-curves for rivaroxaban and dabigatran were performed (n = 10). Ex-vivo: Patients with indication of DOAC treatment (stroke; dabigatran/rivaroxaban) were included (n = 21). Blood samples were analyzed before first intake, at first estimated peak level and at 24 h after first but before following intake and 3 h after 24 h-intake. Standard and modified thromboelastometric-assays, using low tissue factor concentrations (TFTEM) or ecarin (ECATEM) were used. Receiver-operating-characteristics-curve-analysis (ROC), regression-analysis and two-way-ANOVA were performed. RESULTS:In-vitro: TFTEM detected dabigatran and rivaroxaban (ROC_AUC: 0.99; sensitivity/specificity: 100%/98%) but could not discriminate. Dabigatran prolongs CTECATEM whereas rivaroxaban did not. Clotting Time (CT)-ratio TFTEM/ECATEM discriminated highly sensitive (100%) and specific (100%) between dabigatran and rivaroxaban even at very low concentrations (ROC_AUC:1.0). CTECATEM correlated with dabigatran spiked concentrations (r = 0.9985; p < 0.001) and CTTFTEM (r = 0.9363; p = 0.006) with rivaroxaban. Similarly results could be demonstrated with patient data: We confirmed the performance for the differentiation of CT-ratio TFTEM/ECATEM (sensitivity 100%/specificity 100%) at any time after first intake of either DOAC. CONCLUSION:The thromboelastometric tests TFTEM and ECATEM detect and differentiate rivaroxaban and dabigatran. Further investigations evaluate the other DOACs and the differentiation to phenprocoumon. However, results need to be confirmed in a larger study, and especially cut off values for differentiation need to be calculated from a larger sample size.