Andexanet alfa for the reversal of the low-molecular-weight heparin enoxaparin.
| Title: | Andexanet alfa for the reversal of the low-molecular-weight heparin enoxaparin. |
|---|---|
| Authors: | van Haaps TF; Department of Vascular Medicine, Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam, the Netherlands.; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension & Thrombosis, Amsterdam, the Netherlands.; Benz AP; Department of Cardiology, University Medical Center Mainz, Johannes Gutenberg-University, Mainz, Germany.; Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.; Xu L; Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.; Middeldorp S; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.; Eikelboom JW; Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.; Milling TJ Jr; Seton Dell Medical School Stroke Institute, Dell Medical School, University of Texas at Austin, Austin, Texas, USA.; Crowther M; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.; Holer L; AstraZeneca, Gothenburg, Sweden.; Nolan S; Alexion, AstraZeneca, Dublin, Ireland.; Ladenvall P; AstraZeneca, Gothenburg, Sweden.; Lu G; Alexion, AstraZeneca, South San Francisco, California, USA.; Coppens M; Department of Vascular Medicine, Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam, the Netherlands.; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension & Thrombosis, Amsterdam, the Netherlands. |
| Source: | Research and practice in thrombosis and haemostasis [Res Pract Thromb Haemost] 2025 Sep 23; Vol. 9 (7), pp. 103191. Date of Electronic Publication: 2025 Sep 23 (Print Publication: 2025). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: United States NLM ID: 101703775 Publication Model: eCollection Cited Medium: Internet ISSN: 2475-0379 (Electronic) Linking ISSN: 24750379 NLM ISO Abbreviation: Res Pract Thromb Haemost Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Publication: 2023- : [New York] : Elsevier; Original Publication: Hoboken, NJ : John Wiley & Sons, Inc., [2017]- |
| Abstract: | Background: Andexanet alfa (andexanet) is the only approved reversal agent for patients with acute major bleeding during apixaban or rivaroxaban treatment. Its mechanism suggests it may also reverse the effects of low-molecular-weight heparin.; Aim: To evaluate the effects of andexanet in healthy volunteers and in patients with acute major bleeding on enoxaparin.; Methods: In the first study, healthy volunteers received enoxaparin 1 mg/kg twice daily for ≥3 doses and were randomized to receive either andexanet or placebo in high- or low-dose regimens, given 3 hours (high dose) or 8 hours (low dose) after the last dose. In the second study (Andexanet Alfa, a Novel Antidote to the Anticoagulant Effects of FXa Inhibitors 4), dosing depended on timing and amount of last enoxaparin dose: high dose if > 40 mg or 2 hours, while low dose consisted of a 400 mg bolus followed by 480 mg >2 hours. The primary outcome was change in anti-Xa activity. Hemostatic efficacy was assessed in patients with confirmed bleeding and baseline anti-Xa ≥ 0.25 IU/mL.; Results: In the first study, 24 volunteers received andexanet (12 at a high dose and 12 at a low dose), and 7 received a placebo. Median anti-Xa activity decreased by 83% (0.92-0.17 IU/mL) in the high-dose cohort, and by 73% (0.78-0.22 IU/mL) in the low-dose cohort. In the second study, 22 patients received andexanet; anti-Xa activity decreased by 75% (95% CI, 67%-79%; 0.48-0.14 IU/mL). Good/excellent hemostasis was achieved in 14 of 16 assessable patients (88%).; Conclusion: In enoxaparin-treated subjects, andexanet reduced anti-Xa activity and achieved effective hemostasis in 88% of patients. Results align with findings of patients using apixaban, rivaroxaban, or edoxaban.; (© 2025 The Author(s).) |
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| Contributed Indexing: | Keywords: andexanetalfa; enoxaparin; hemorrhage; heparin, low-molecular-weight; intracranial hemorrhages; venous thromboembolism |
| Entry Date(s): | Date Created: 20251027 Date Completed: 20251027 Latest Revision: 20251029 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12552982 |
| DOI: | 10.1016/j.rpth.2025.103191 |
| PMID: | 41141842 |
| Database: | MEDLINE |
Journal Article