Andexanet Alfa for Reversal of Factor Xa Inhibitors in Intracranial Hemorrhage: Observational Cohort Study
Background: Intracranial hemorrhage (ICH) is associated with high mortality and morbidity, especially in patients under anticoagulative treatment. Andexanet alfa (AA) is a modified recombinant form of human factor Xa (FXa) developed for reversal of FXa-inhibitors, e.g., in the event of ICH, but expe...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-06-01
|
| Series: | Journal of Clinical Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0383/11/12/3399 |
| _version_ | 1797486053513232384 |
|---|---|
| author | Sebastian Rauch Hans-Peter Müller Jens Dreyhaupt Albert C. Ludolph Jan Kassubek Katharina Althaus |
| author_facet | Sebastian Rauch Hans-Peter Müller Jens Dreyhaupt Albert C. Ludolph Jan Kassubek Katharina Althaus |
| author_sort | Sebastian Rauch |
| collection | DOAJ |
| description | Background: Intracranial hemorrhage (ICH) is associated with high mortality and morbidity, especially in patients under anticoagulative treatment. Andexanet alfa (AA) is a modified recombinant form of human factor Xa (FXa) developed for reversal of FXa-inhibitors, e.g., in the event of ICH, but experience is still limited. Methods: This monocentric retrospective observational cohort study included 46 patients with acute FXa-inhibitor-associated non-traumatic ICH (FXa-I-ICH) of whom 23 were treated with AA within 12 h after symptom onset, compared to 23 patients with usual care (UC). Volumetrically analyzed hematoma expansion (HE) in brain imaging, clinical outcome and incidence of adverse events were analyzed. Results: All patients (mean age 79.8 ± 7.2 years) were effectively anticoagulated. The cohort included severely ill patients with large hematoma volumes (median 20.4, IQR 7.8–39.0 mL). Efficacy, as assessed by HE in imaging, was very good in the AA-group. There was no (0.0%) relevant HE (>33%) in contrast to UC-group (26.1%). Nevertheless, we observed a high incidence of thromboembolic events (30.4% vs. 4.4%) and non-favorable outcomes (death/palliative condition) in 43.5% vs. 26.1%. Conclusions: There was no HE in the volumetric neuroimaging assessment in the AA-group, but clinical outcomes remained often worse. Large randomized trials for the use of AA in patients with acute FXa-inhibitor-associated ICH are needed to investigate the clinical outcome in consideration of the rates of thromboembolism. |
| first_indexed | 2024-03-09T23:27:41Z |
| format | Article |
| id | doaj.art-cb8e44327d794b38babeecdbbb883ffa |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T23:27:41Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-cb8e44327d794b38babeecdbbb883ffa2023-11-23T17:15:21ZengMDPI AGJournal of Clinical Medicine2077-03832022-06-011112339910.3390/jcm11123399Andexanet Alfa for Reversal of Factor Xa Inhibitors in Intracranial Hemorrhage: Observational Cohort StudySebastian Rauch0Hans-Peter Müller1Jens Dreyhaupt2Albert C. Ludolph3Jan Kassubek4Katharina Althaus5Department of Neurology, University of Ulm, 89081 Ulm, GermanyDepartment of Neurology, University of Ulm, 89081 Ulm, GermanyInstitute of Epidemiology and Medical Biometry, University of Ulm, 89081 Ulm, GermanyDepartment of Neurology, University of Ulm, 89081 Ulm, GermanyDepartment of Neurology, University of Ulm, 89081 Ulm, GermanyDepartment of Neurology, University of Ulm, 89081 Ulm, GermanyBackground: Intracranial hemorrhage (ICH) is associated with high mortality and morbidity, especially in patients under anticoagulative treatment. Andexanet alfa (AA) is a modified recombinant form of human factor Xa (FXa) developed for reversal of FXa-inhibitors, e.g., in the event of ICH, but experience is still limited. Methods: This monocentric retrospective observational cohort study included 46 patients with acute FXa-inhibitor-associated non-traumatic ICH (FXa-I-ICH) of whom 23 were treated with AA within 12 h after symptom onset, compared to 23 patients with usual care (UC). Volumetrically analyzed hematoma expansion (HE) in brain imaging, clinical outcome and incidence of adverse events were analyzed. Results: All patients (mean age 79.8 ± 7.2 years) were effectively anticoagulated. The cohort included severely ill patients with large hematoma volumes (median 20.4, IQR 7.8–39.0 mL). Efficacy, as assessed by HE in imaging, was very good in the AA-group. There was no (0.0%) relevant HE (>33%) in contrast to UC-group (26.1%). Nevertheless, we observed a high incidence of thromboembolic events (30.4% vs. 4.4%) and non-favorable outcomes (death/palliative condition) in 43.5% vs. 26.1%. Conclusions: There was no HE in the volumetric neuroimaging assessment in the AA-group, but clinical outcomes remained often worse. Large randomized trials for the use of AA in patients with acute FXa-inhibitor-associated ICH are needed to investigate the clinical outcome in consideration of the rates of thromboembolism.https://www.mdpi.com/2077-0383/11/12/3399coagulantsfactor Xa inhibitorshemorrhageintracranial hemorrhagesantidoteandexanet alfa |
| spellingShingle | Sebastian Rauch Hans-Peter Müller Jens Dreyhaupt Albert C. Ludolph Jan Kassubek Katharina Althaus Andexanet Alfa for Reversal of Factor Xa Inhibitors in Intracranial Hemorrhage: Observational Cohort Study Journal of Clinical Medicine coagulants factor Xa inhibitors hemorrhage intracranial hemorrhages antidote andexanet alfa |
| title | Andexanet Alfa for Reversal of Factor Xa Inhibitors in Intracranial Hemorrhage: Observational Cohort Study |
| title_full | Andexanet Alfa for Reversal of Factor Xa Inhibitors in Intracranial Hemorrhage: Observational Cohort Study |
| title_fullStr | Andexanet Alfa for Reversal of Factor Xa Inhibitors in Intracranial Hemorrhage: Observational Cohort Study |
| title_full_unstemmed | Andexanet Alfa for Reversal of Factor Xa Inhibitors in Intracranial Hemorrhage: Observational Cohort Study |
| title_short | Andexanet Alfa for Reversal of Factor Xa Inhibitors in Intracranial Hemorrhage: Observational Cohort Study |
| title_sort | andexanet alfa for reversal of factor xa inhibitors in intracranial hemorrhage observational cohort study |
| topic | coagulants factor Xa inhibitors hemorrhage intracranial hemorrhages antidote andexanet alfa |
| url | https://www.mdpi.com/2077-0383/11/12/3399 |
| work_keys_str_mv | AT sebastianrauch andexanetalfaforreversaloffactorxainhibitorsinintracranialhemorrhageobservationalcohortstudy AT hanspetermuller andexanetalfaforreversaloffactorxainhibitorsinintracranialhemorrhageobservationalcohortstudy AT jensdreyhaupt andexanetalfaforreversaloffactorxainhibitorsinintracranialhemorrhageobservationalcohortstudy AT albertcludolph andexanetalfaforreversaloffactorxainhibitorsinintracranialhemorrhageobservationalcohortstudy AT jankassubek andexanetalfaforreversaloffactorxainhibitorsinintracranialhemorrhageobservationalcohortstudy AT katharinaalthaus andexanetalfaforreversaloffactorxainhibitorsinintracranialhemorrhageobservationalcohortstudy |