ArticlePloS one2018
Andexanet alfa effectively reverses edoxaban anticoagulation effects and associated bleeding in a rabbit acute hemorrhage model.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 33 citations in OpenAlex.
- Reversal of Direct Oral Anticoagulants (DOACs) for Critical Bleeding or Urgent Procedures.Journal of clinical medicine · 2025Review
- Andexanet alfa therapy showed No increased rate of thromboembolic events in spontaneous intracranial hemorrhage patients: A multicenter electronic health record study.World neurosurgery: X · 2024Article
- Reversal and resumption of anticoagulants in patients with anticoagulant-associated intracerebral hemorrhage.European journal of medical research · 2024Review
- Anticoagulant Reversal in Gastrointestinal Bleeding: Review of Treatment Guidelines.Digestive diseases and sciences · 2021Review
- Role of direct oral anticoagulants in patients with kidney disease.Kidney international · 2020Review
- Direct oral anticoagulants: a review on the current role and scope of reversal agents.Journal of thrombosis and thrombolysis · 2020Review
- Andexanet Alfa and its Clinical Application.Heart international · 2020Review
- Anticoagulation of Cardiovascular Conditions in the Cancer Patient: Review of Old and New Therapies.Current oncology reports · 2019Review
- Edoxaban for Venous Thromboembolism Treatment-The New Kid on The Block for Latin America. A Practical Guide.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis · 2018Review
- Andexanet Alfa: First Global Approval.Drugs · 2018Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionIncreasing use of factor Xa (FXa) inhibitors necessitates effective reversal agents to manage bleeding. Andexanet alfa, a novel modified recombinant human FXa, rapidly reverses the anticoagulation effects of direct and indirect FXa inhibitors.
objectiveTo evaluate the ability of andexanet to reverse anticoagulation in vitro and reduce bleeding in rabbits administered edoxaban. MATERIALS AND
methodsIn vitro studies characterized the interaction of andexanet with edoxaban and its ability to reverse edoxaban-mediated anti-FXa activity. In a rabbit model of surgically induced, acute hemorrhage, animals received edoxaban vehicle+andexanet vehicle (control), edoxaban (1 mg/kg)+andexanet vehicle, edoxaban+andexanet (75 mg, 5-minute infusion, 20 minutes after edoxaban), or edoxaban vehicle+andexanet prior to injury.
resultsAndexanet bound edoxaban with high affinity similar to FXa. Andexanet rapidly and dose-dependently reversed the effects of edoxaban on FXa activity and coagulation pharmacodynamic parameters in vitro. In edoxaban-anticoagulated rabbits, andexanet reduced anti-FXa activity by 82% (from 548±87 to 100±41 ng/ml; P<0.0001), mean unbound edoxaban plasma concentration by ~80% (from 100±10 to 21±6 ng/ml; P<0.0001), and blood loss by 80% vs. vehicle (adjusted for control, 2.6 vs. 12.9 g; P = 0.003). The reduction in blood loss correlated with the decrease in anti-FXa activity (r = 0.6993, P<0.0001) and unbound edoxaban (r = 0.5951, P = 0.0035).
conclusionThese data demonstrate that andexanet rapidly reversed the anticoagulant effects of edoxaban, suggesting it could be clinically valuable for the management of acute and surgery-related bleeding. Correlation of blood loss with anti-FXa activity supports the use of anti-FXa activity as a biomarker for assessing anticoagulation reversal in clinical trials.
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