Dose-Related Effectiveness of Andexanet Alfa for Reversal of Apixaban Anticoagulation in a Porcine Polytrauma Model.
Journal
Thrombosis and haemostasis
ISSN: 2567-689X
Titre abrégé: Thromb Haemost
Pays: Germany
ID NLM: 7608063
Informations de publication
Date de publication:
21 Aug 2023
21 Aug 2023
Historique:
medline:
22
8
2023
pubmed:
22
8
2023
entrez:
21
8
2023
Statut:
aheadofprint
Résumé
Andexanet alfa (andexanet) is a reversal agent for use in patients with life-threatening or uncontrolled bleeding treated with oral factor Xa (FXa) inhibitors. There are limited data on the dose-response relationship of andexanet and FXa inhibitor-related bleeding. The aim of this study was to assess the dose-related effectiveness of andexanet in reducing blood loss, improving survival, and reversing apixaban anticoagulation in a porcine polytrauma model. Apixaban was given orally to 40 male pigs for 3 days at a dose of 20 mg/d. On day 3, following bilateral femur fractures and blunt liver injury, animals ( Administration of 250-mg bolus + 300-mg infusion, andexanet 500-mg bolus, and 500-mg bolus + 600-mg infusion significantly decreased total blood loss by 37, 58, and 61%, respectively (all In a porcine polytrauma model with major bleeding on apixaban, andexanet dose dependently decreased anti-FXa activity. Lower anti-FXa levels (<50 ng/mL) with andexanet 500-mg bolus ± infusion were correlated with 60% less blood loss and 100% survival versus controls.
Sections du résumé
BACKGROUND
BACKGROUND
Andexanet alfa (andexanet) is a reversal agent for use in patients with life-threatening or uncontrolled bleeding treated with oral factor Xa (FXa) inhibitors. There are limited data on the dose-response relationship of andexanet and FXa inhibitor-related bleeding.
OBJECTIVE
OBJECTIVE
The aim of this study was to assess the dose-related effectiveness of andexanet in reducing blood loss, improving survival, and reversing apixaban anticoagulation in a porcine polytrauma model.
METHODS
METHODS
Apixaban was given orally to 40 male pigs for 3 days at a dose of 20 mg/d. On day 3, following bilateral femur fractures and blunt liver injury, animals (
RESULTS
RESULTS
Administration of 250-mg bolus + 300-mg infusion, andexanet 500-mg bolus, and 500-mg bolus + 600-mg infusion significantly decreased total blood loss by 37, 58, and 61%, respectively (all
CONCLUSION
CONCLUSIONS
In a porcine polytrauma model with major bleeding on apixaban, andexanet dose dependently decreased anti-FXa activity. Lower anti-FXa levels (<50 ng/mL) with andexanet 500-mg bolus ± infusion were correlated with 60% less blood loss and 100% survival versus controls.
Identifiants
pubmed: 37604188
doi: 10.1055/s-0043-1772697
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Thieme. All rights reserved.
Déclaration de conflit d'intérêts
F.R. and T.B. have no conflicts of interest to declare. H.S. has received honoraria for participation in advisory board meetings for Bayer Healthcare, Boehringer Ingelheim, and TEM International. He has also received speaker fees from Haemonetics and Vifor, and study grants from CSL Behring. R.R. has received honoraria for consulting or lecturing from CSL Behring, Boehringer Ingelheim and Fresenius. O.G. has received research funding from Abiomed, AstraZeneca, Alveron, Bayer Healthcare, Biotest, Boehringer Ingelheim, CSL Behring, Ferring, Octapharma, Novo Nordisk, Nycomed, and Portola. He has also received honoraria for lectures and consultancy support from Abiomed, AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, CSL Behring, Octapharma, Sanofi, Shire, Takeda, Pfizer, and Portola.