Impact of Idarucizumab and Andexanet Alfa on DOAC Plasma Concentration and ClotPro<sup>®</sup> Clotting Time: An Ex Vivo Spiking Study in A Cohort of Trauma Patients
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...
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MDPI AG
2021-08-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/10/16/3476 |
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| author | Daniel Oberladstätter Christoph J. Schlimp Johannes Zipperle Marcin F. Osuchowski Wolfgang Voelckel Oliver Grottke Herbert Schöchl |
| author_facet | Daniel Oberladstätter Christoph J. Schlimp Johannes Zipperle Marcin F. Osuchowski Wolfgang Voelckel Oliver Grottke Herbert Schöchl |
| author_sort | Daniel Oberladstätter |
| collection | DOAJ |
| description | 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<sup>®</sup> 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<sup>®</sup> 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, <i>p</i> < 0.001). Andexanet alfa decreased the apixaban concentration from 165.1 ± 65.5 ng/mL to 9.8 ± 8.1 ng/mL, edoxaban from 152.4 ± 79.0 ng/mL to 36.4 ± 19.2 ng/mL, and rivaroxaban from 153.2 ± 111.8 ng/mL to 18.1 ± 9.1 ng/mL (all <i>p</i> < 0.001). Andexanet alfa shortened the RVV-CT of patients with apixaban from 239.2 ± 71.7 s to 151.1 ± 30.2 s, edoxaban from 288.2 ± 65.0 s to 122.7 ± 37.1 s, and rivaroxaban from 225.9 ± 49.3 s to 103.7 ± 12.1 s (all <i>p</i> < 0.001). In vitro spiking of dabigatran-containing blood with Idarucizumab substantially reduced the plasma concentration and ecarin-test clotting time. Andexanet alfa lowered the concentration of the investigated factor Xa-inhibitors but did not normalize the RVV-CT. In healthy volunteers’ blood, Idarucizumab spiking had no impact on ECA-CT. Andexanet alfa spiking of non-anticoagulated blood prolonged RVV-CT (<i>p</i> = 0.001), potentially as a consequence of a competitive antagonism with human factor Xa. |
| first_indexed | 2024-03-10T08:42:35Z |
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| spelling | doaj.art-125a89a391eb48a88a8422e51e78d9162023-11-22T08:08:49ZengMDPI AGJournal of Clinical Medicine2077-03832021-08-011016347610.3390/jcm10163476Impact of Idarucizumab and Andexanet Alfa on DOAC Plasma Concentration and ClotPro<sup>®</sup> Clotting Time: An Ex Vivo Spiking Study in A Cohort of Trauma PatientsDaniel Oberladstätter0Christoph J. Schlimp1Johannes Zipperle2Marcin F. Osuchowski3Wolfgang Voelckel4Oliver Grottke5Herbert Schöchl6AUVA Trauma Centre Salzburg, Department of Anaesthesiology and Intensive Care Medicine, Academic Teaching Hospital of the Paracelsus Medical University, 5020 Salzburg, AustriaAUVA Trauma Research Centre, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, 1200 Vienna, AustriaAUVA Trauma Research Centre, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, 1200 Vienna, AustriaAUVA Trauma Research Centre, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, 1200 Vienna, AustriaAUVA Trauma Centre Salzburg, Department of Anaesthesiology and Intensive Care Medicine, Academic Teaching Hospital of the Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Anaesthesiology, RWTH Aachen University Hospital, 52074 Aachen, GermanyAUVA Trauma Centre Salzburg, Department of Anaesthesiology and Intensive Care Medicine, Academic Teaching Hospital of the Paracelsus Medical University, 5020 Salzburg, AustriaSpecific 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<sup>®</sup> 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<sup>®</sup> 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, <i>p</i> < 0.001). Andexanet alfa decreased the apixaban concentration from 165.1 ± 65.5 ng/mL to 9.8 ± 8.1 ng/mL, edoxaban from 152.4 ± 79.0 ng/mL to 36.4 ± 19.2 ng/mL, and rivaroxaban from 153.2 ± 111.8 ng/mL to 18.1 ± 9.1 ng/mL (all <i>p</i> < 0.001). Andexanet alfa shortened the RVV-CT of patients with apixaban from 239.2 ± 71.7 s to 151.1 ± 30.2 s, edoxaban from 288.2 ± 65.0 s to 122.7 ± 37.1 s, and rivaroxaban from 225.9 ± 49.3 s to 103.7 ± 12.1 s (all <i>p</i> < 0.001). In vitro spiking of dabigatran-containing blood with Idarucizumab substantially reduced the plasma concentration and ecarin-test clotting time. Andexanet alfa lowered the concentration of the investigated factor Xa-inhibitors but did not normalize the RVV-CT. In healthy volunteers’ blood, Idarucizumab spiking had no impact on ECA-CT. Andexanet alfa spiking of non-anticoagulated blood prolonged RVV-CT (<i>p</i> = 0.001), potentially as a consequence of a competitive antagonism with human factor Xa.https://www.mdpi.com/2077-0383/10/16/3476DOACreversalIdarucizumabAndexanet alfaRVV-testECA-test |
| spellingShingle | Daniel Oberladstätter Christoph J. Schlimp Johannes Zipperle Marcin F. Osuchowski Wolfgang Voelckel Oliver Grottke Herbert Schöchl Impact of Idarucizumab and Andexanet Alfa on DOAC Plasma Concentration and ClotPro<sup>®</sup> Clotting Time: An Ex Vivo Spiking Study in A Cohort of Trauma Patients Journal of Clinical Medicine DOAC reversal Idarucizumab Andexanet alfa RVV-test ECA-test |
| title | Impact of Idarucizumab and Andexanet Alfa on DOAC Plasma Concentration and ClotPro<sup>®</sup> Clotting Time: An Ex Vivo Spiking Study in A Cohort of Trauma Patients |
| title_full | Impact of Idarucizumab and Andexanet Alfa on DOAC Plasma Concentration and ClotPro<sup>®</sup> Clotting Time: An Ex Vivo Spiking Study in A Cohort of Trauma Patients |
| title_fullStr | Impact of Idarucizumab and Andexanet Alfa on DOAC Plasma Concentration and ClotPro<sup>®</sup> Clotting Time: An Ex Vivo Spiking Study in A Cohort of Trauma Patients |
| title_full_unstemmed | Impact of Idarucizumab and Andexanet Alfa on DOAC Plasma Concentration and ClotPro<sup>®</sup> Clotting Time: An Ex Vivo Spiking Study in A Cohort of Trauma Patients |
| title_short | Impact of Idarucizumab and Andexanet Alfa on DOAC Plasma Concentration and ClotPro<sup>®</sup> Clotting Time: An Ex Vivo Spiking Study in A Cohort of Trauma Patients |
| title_sort | impact of idarucizumab and andexanet alfa on doac plasma concentration and clotpro sup r sup clotting time an ex vivo spiking study in a cohort of trauma patients |
| topic | DOAC reversal Idarucizumab Andexanet alfa RVV-test ECA-test |
| url | https://www.mdpi.com/2077-0383/10/16/3476 |
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