ArticleResearch and practice in thrombosis and haemostasis2020
Andexanet versus prothrombin complex concentrates: Differences in reversal of factor Xa inhibitors in in vitro thrombin generation.
Article in Research and practice in thrombosis and haemostasis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
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
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Andexanet alpha versus four-factor prothrombin complex concentrate in DOACs anticoagulation reversal: an updated systematic review and meta-analysis.Critical care (London, England) · 2024Pooled it
- Trial
- Effect of PCC on thrombin generation in patients on FXaI with bleeding or needing urgent surgery (GAUGE).Blood advances · 2026Observational
- Thrombosis and Survival after Prothrombin Complex Concentrate Use to treat Oral Anticoagulant Associated Haemorrhage.The Ulster medical journal · 2026Observational
- Coagulation assays for assessing the bypassing of factor Xa direct oral anticoagulants using VMX-C001.Research and practice in thrombosis and haemostasis · 2026Article
- Article
- Multidisciplinary Expert Guidance for the Management of Severe Bleeding on Oral Anticoagulation: An Algorithm for Practicing Clinicians.Thrombosis and haemostasis · 2025Review
- Management of factor Xa inhibitor-related traumatic non-intracranial bleeding events with andexanet alfa or four-factor prothrombin complex concentrate in a US multicenter observational study.Journal of the American College of Emergency Physicians open · 2024Article
- The Efficacy of Andexanet Alfa for the Reversal of Factor Xa Inhibitors Is Not Influenced by Hemodilution with Different Volume Expanders.Journal of clinical medicine · 2024Article
- 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
- Treatment of Factor-Xa Inhibitor-associated Bleeding with Andexanet Alfa or 4 Factor PCC: A Multicenter Feasibility Retrospective Study.The western journal of emergency medicine · 2023Observational
- Effect of PCC on Thrombin Generation among Patients on Factor Xa Inhibitors with Major Bleeding or Needing Urgent Surgery (GAUGE): Design and Rationale.TH open : companion journal to thrombosis and haemostasis · 2023Article
- Response to the Letter by Spurling and Colleagues.Critical care (London, England) · 2023Article
- Novel strategies in antithrombotic therapy: targeting thrombosis while preserving hemostasis.Frontiers in cardiovascular medicine · 2023Review
- In vitro reversal of direct factor Xa inhibitors: Direct comparison of andexanet alfa and prothrombin complex concentrates Cofact and Beriplex/Kcentra.Research and practice in thrombosis and haemostasis · 2022Article
- New agents for DOAC reversal: a practical management review.The British journal of cardiology · 2022Article
- Andexanet versus prothrombin complex concentrates: Differences in reversal of factor Xa inhibitors in in vitro thrombin generation.Research and practice in thrombosis and haemostasis · 2020Article
- Retrospective Comparison of Andexanet Alfa and 4-Factor Prothrombin Complex for Reversal of Factor Xa-Inhibitor Related Bleeding.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
- 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
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAndexanet alfa (andexanet) is a modified human factor Xa (FXa) approved for anticoagulation reversal in patients with life-threatening bleeding treated with rivaroxaban or apixaban. Four-factor prothrombin complex concentrates (4F-PCCs) are approved for reversal of vitamin K antagonist-induced anticoagulation but not FXa inhibitors. The mechanism and effectiveness of 4F-PCCs for FXa inhibitor reversal are unclear.
objectiveTo investigate the mechanism and impact of 4F-PCCs on reversal of rivaroxaban and apixaban in vitro compared to andexanet.
methodsThe effect of 4F-PCCs (or individual factors) on tissue factor-initiated thrombin generation (TF-TG) was evaluated in human plasma, with or without rivaroxaban or apixaban, and compared with andexanet under the same conditions.
resultsIn the TF-TG assay, 4F-PCC completely reversed warfarin anticoagulation. Andexanet normalized TF-TG over a wide range of apixaban and rivaroxaban concentrations tested (19-2000 ng/mL). However, 4F-PCC (or individual factors) was unable to normalize endogenous thrombin potential (ETP) or peak thrombin (Peak) in the presence of apixaban or rivaroxaban (75-500 ng/mL). TF-TG was only normalized by 4F-PCC at inhibitor concentrations <75 ng/mL (ETP) or <37.5 ng/mL (Peak). These data can be explained by the estimated thresholds of FXa activity required to support normal TF-TG based on the inhibitor:FXa ratios and levels of uninhibited FXa. The data are consistent with healthy volunteer studies where TF-TG is not normalized until inhibitor levels are substantially decreased.
conclusionsBoth the theoretical calculations and experimental data demonstrated that 4F-PCCs are only able to normalize TG over a low and narrow range of FXa inhibitor concentrations (<75 ng/mL).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.