Assessment of the effect of direct oral anticoagulants dabigatran, rivaroxaban, and apixaban in healthy male volunteers using a thrombin generation assay

Background: There are clinical situations where monitoring direct oral anticoagulants (DOACs) may be useful. The clinical application of thrombin generation assay (TGA) in monitoring the effect of DOACs has not been well established. An ex vivo study was performed to systematically evaluate the anticoagulant effect of dabigatran, rivaroxaban and apixaban on each individual TGA parameter through serial measurements over time to assess suitability of these parameters for monitoring the anticoagulant effect of DOACs. Methods: Ten healthy volunteers were given oral dabigatran 150 mg, rivaroxaban 20 mg, or apixaban 10 mg once. TGA parameters lag time, endogenous Thrombin potential (ETP), and thrombin peak height, time to peak, and velocity index were measured at times 0, 2, 4, and 24 hours after intake of DOAC. TGA parameters and DOAC concentrations were correlated. Results: The lag time was significantly correlated with all DOAC concentrations (r >= .81, P < .0001 for all). Thrombin peak height best correlated with direct Factor Xa inhibitor (FXa) concentrations in nonlinear fashion (R (2) >= .87). ETP was weakly correlated with DOAC levels (r <= .68). Besides lag time, the other TGA parameters were not significantly altered over time by dabigatran. Conclusion: Lag time was the only sensitive TGA parameter across the different classes of DOACs evaluated. Thrombin peak height was strongly correlated to FXa inhibitor concentrations and potentially a useful parameter to monitor FXa inhibitors at low concentrations. ETP had a weak correlation with achieved DOAC concentrations and is likely less suitable for assessment of DOAC effect as a stand-alone parameter.