Impact of Idarucizumab and Andexanet Alfa on DOAC Plasma Concentration and ClotPro^® Clotting Time: An Ex Vivo Spiking Study in A Cohort of Trauma Patients

Abstract

Specific antagonists have been developed for the reversal of direct oral anticoagulants (DOAC). We investigated the impact of these reversal agents on the plasma concentration and visco-elastic test results of dabigatran and factor Xa inhibitors. After baseline measurements of dabigatran, the plasma concentration, and the visco-elastic ClotPro® ecarin clotting time (ECA-CT), we added the reversal agent Idarucizumab in vitro and these two analyses were repeated. Likewise, the baseline plasma concentration of apixaban, edoxaban, and rivaroxaban as well as ClotPro® Russell’s viper venom test clotting time (RVV-CT) were measured and reanalyzed following Andexanet alfa spiking. We analyzed fifty blood samples from 37 patients and 10 healthy volunteers. Idarucizumab decreased the measured dabigatran plasma concentration from 323.9 ± 185.4 ng/mL to 5.9 ± 2.3 ng/mL and ECA-CT from 706.2 ± 344.6 s to 70.6 ± 20.2 s, (all, p p p p = 0.001), potentially as a consequence of a competitive antagonism with human factor Xa.

Keywords

• DOAC
• reversal
• Idarucizumab
• Andexanet alfa
• RVV-test
• ECA-test