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

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. 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