{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T17:46:40Z","timestamp":1781200000253,"version":"3.54.1"},"reference-count":32,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>\n            Background\u2003Andexanet 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\u2013response relationship of andexanet and FXa inhibitor-related bleeding.<\/jats:p><jats:p>\n            Objective\u2003The 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.<\/jats:p><jats:p>\n            Methods\u2003Apixaban was given orally to 40 male pigs for 3 days at a dose of 20\u2009mg\/d. On day 3, following bilateral femur fractures and blunt liver injury, animals (n\u2009=\u20098\/group) received andexanet (250-mg bolus, 250-mg bolus\u2009+\u2009300-mg 2-hour infusion, 500-mg bolus, or 500-mg bolus\u2009+\u2009600-mg 2-hour infusion) or vehicle (control). Total blood loss was the primary endpoint. Coagulation parameters were assessed for 300\u2009minutes or until death. Data were analyzed with a mixed-model analysis of variance.<\/jats:p><jats:p>\n            Results\u2003Administration of 250-mg bolus\u2009+\u2009300-mg infusion, andexanet 500-mg bolus, and 500-mg bolus\u2009+\u2009600-mg infusion significantly decreased total blood loss by 37, 58, and 61%, respectively (all p\u2009&lt;\u20090.0001), with 100% survival. Andexanet 250-mg bolus was ineffective in reducing total blood loss (6%) and mortality (63% survival) versus controls. Andexanet 500-mg bolus\u2009\u00b1\u2009infusion neutralized anti-FXa activity to less than 50\u2009ng\/mL. Andexanet neutralization of thrombin generation and thromboelastometry parameters was dose and infusion time dependent.<\/jats:p><jats:p>\n            Conclusion\u2003In a porcine polytrauma model with major bleeding on apixaban, andexanet dose dependently decreased anti-FXa activity. Lower anti-FXa levels (&lt;50\u2009ng\/mL) with andexanet 500-mg bolus\u2009\u00b1\u2009infusion were correlated with 60% less blood loss and 100% survival versus controls.<\/jats:p>","DOI":"10.1055\/s-0043-1772697","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T23:01:58Z","timestamp":1692658918000},"page":"020-031","source":"Crossref","is-referenced-by-count":2,"title":["Dose-Related Effectiveness of Andexanet Alfa for Reversal of Apixaban Anticoagulation in a Porcine Polytrauma Model"],"prefix":"10.1055","volume":"124","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0345-9442","authenticated-orcid":false,"given":"Farahnaz","family":"Rayatdoost","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, RWTH Aachen University Hospital, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till","family":"Braunschweig","sequence":"additional","affiliation":[{"name":"Department of Pathology, RWTH Aachen University Hospital, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert","family":"Sch\u00f6chl","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Medicine, AUVA Trauma Centre Salzburg, Academic Teaching Hospital of the Paracelsus Medical University Salzburg, Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Rossaint","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, RWTH Aachen University Hospital, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Grottke","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, RWTH Aachen University Hospital, Aachen, 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