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

摘要

Abstract Essentials The value of thrombin generation assay (TGA) in monitoring direct oral anticoagulants (DOAC) is not well defined. TGA parameters were measured and correlated to DOAC levels in 10 healthy volunteers after oral intake of DOACs. Lag time is the only sensitive TGA parameter across different DOACs, dabigatran, rivaroxaban and apixaban. Endogenous thrombin potential had weak correlation with DOAC levels and not suitable as stand-alone parameter. BackgroundThere 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. MethodsTen 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. ResultsThe lag time was significantly correlated with all DOAC concentrations ( r ≥?.81, P ConclusionLag 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.