ArticleBlood advances2018
Comparison of reversal activity and mechanism of action of UHRA, andexanet, and PER977 on heparin and oral FXa inhibitors.
Article in Blood advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 64 citations in OpenAlex.
- Use of Andexanet Alfa to Reverse Heparin After Cardiopulmonary Bypass.Annals of thoracic surgery short reports · 2025Article
- Procoagulant off-target effect of the direct oral anticoagulant reversal agent Andexanet alfa.Blood vessels, thrombosis & hemostasis · 2025Article
- Platelet Polyphosphate Signals Through NFκB to Induce Myofibroblast Differentiation.Biomolecules · 2025Article
- Efficient Small-Molecule Reversal Agents for Anticoagulant Fondaparinux.ACS pharmacology & translational science · 2025Article
- Oral Anticoagulation Therapy: An Update on Usage and Costs in the Endemic COVID-19 Era.Journal of clinical medicine · 2025Article
- Andexanet Alfa-Associated Heparin Resistance in Cardiac Surgery: Mechanism and In Vitro Perspectives.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Reversal and resumption of anticoagulants in patients with anticoagulant-associated intracerebral hemorrhage.European journal of medical research · 2024Review
- ANMCO/SIMEU consensus document on the use of reversal agents for antithrombotic therapies in patients with ongoing bleeding or at high risk of haemorrhagic events.European heart journal supplements : journal of the European Society of Cardiology · 2024Article
- Andexanet alpha-induced heparin resistance treated by nafamostat mesylate in a patient undergoing total aortic arch repair for Stanford type A acute aortic dissection: a case report.JA clinical reports · 2024Article
- Influence of Steric Shield on Biocompatibility and Antithrombotic Activity of Dendritic Polyphosphate Inhibitor.Molecular pharmaceutics · 2022Article
- Dynamic Combinatorial Optimization ofJournal of medicinal chemistry · 2022Article
- Understanding the Interaction of Polyelectrolyte Architectures with Proteins and Biosystems.Angewandte Chemie (International ed. in English) · 2021Review
- Heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene.Chemical science · 2020Article
- Difficult Intraoperative Heparinization Following Andexanet Alfa Administration.Clinical practice and cases in emergency medicine · 2019Article
- Andexanet Alfa Neutralizes the Anticoagulant Effects of Unfractionated Heparin of Bovine, Ovine and Porcine Origin Almost as Protamine Sulfate.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
- Differential Neutralization of Apixaban, Betrixaban, Edoxaban, and Rivaroxaban by Andexanet Alfa as Measured by Whole Blood Thromboelastographic Analysis.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
- Differential Neutralization of Unfractionated Heparin and Enoxaparin by Andexanet Alfa.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
- Assay-Based Differentiation in the Neutralization Profile of Unfractionated Heparin, Enoxaparin, and Fondaparinux by Andexanet Alfa.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Anticoagulants such as unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and direct oral anticoagulants (DOACs) targeting thrombin (IIa) or factor Xa (FXa) are widely used in prevention and treatment of thromboembolic disorders. However, anticoagulant-associated bleeding is a concern that demands monitoring and neutralization. Protamine, the UFH antidote, has limitations, while there is no antidote available for certain direct FXa inhibitors. Improved antidotes in development include UHRA (Universal Heparin Reversal Agent) for all heparin anticoagulants; andexanet alfa (andexanet), a recombinant antidote for both direct FXa inhibitors and LMWHs; and ciraparantag (PER977), a small-molecule antidote for UFH, LMWHs, and certain DOACs. The binding affinities of these antidotes for their presumed anticoagulant targets have not been compared. Here, isothermal titration calorimetry (ITC) was used to determine the affinity of each antidote for its putative targets. Clotting and chromogenic FXa assays were used to characterize neutralization activity, and electron microscopy was used to visualize the effect of each antidote on clot morphology in the absence or presence of anticoagulant. ITC confirmed binding of UHRA to all heparins, and binding of andexanet to edoxaban and rivaroxaban, and to the antithrombin-enoxaparin complex. PER977 was found to bind heparins weakly, but not the direct FXa inhibitors studied. For UHRA and andexanet, an affinity at or below the micromolar level was found to correlate with neutralization activity, while no reversal activity was observed for the PER977/anticoagulant systems. Standard metrics of clot structure were found to correlate weakly with PER977's activity. This is the first study comparing 3 antidotes in development, with each exerting activity through a distinct mechanism.
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Registered trials
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