ArticleJournal of thrombosis and haemostasis : JTH2022
Major bleeding during oral anticoagulant therapy associated with factor V activation by factor Xa.
Article in Journal of thrombosis and haemostasis : JTH, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 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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Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- Effect of PCC on thrombin generation in patients on FXaI with bleeding or needing urgent surgery (GAUGE).Blood advances · 2026Observational
- 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
- Major bleeding during oral anticoagulant therapy associated with factor V activation by factor Xa.Journal of thrombosis and haemostasis : JTH · 2022Article
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
objectivePlasma thrombin generation (TG) provides important information on coagulation status; however, current TG output parameters do not predict major bleeding of patients on anticoagulants. We recently reported that factor V (FV) activation by factor X (FX)a contributes importantly to the initiation phase of TG. Here we investigated how this pathway varies in the normal population and whether FXa-mediated activation of FV is associated with major bleeding in patients on anticoagulant therapy. APPROACH: We employed TIX-5, a specific inhibitor of FV activation by FXa, to estimate the contribution of FXa-mediated FV activation to tissue factor (TF)-initiated TG.
resultsWe show that the contribution of this pathway to plasma TG varies considerably in the normal population, as measured by the time needed to form the first traces of thrombin (TG lag time; mean prolongation by TIX-5 40%, range 0%-116%). Comparing patients on vitamin K antagonists (VKA) of the BLEED study (263 patients with and 538 patients without major bleeding), showed a marked prolongation in the median TG lag time in the presence of TIX-5 in cases (12.83 versus 11.00 minutes, P = 0.0030), while the TG lag time without TIX-5 only showed a minor although significant difference (5.83 vs. 5.67 minutes, P = 0.0198). The TIX-5 sensitivity (lag time + TIX-5/lag time + vehicle) in the upper quartile was associated with a 1.62-fold (95% confidence interval 1.04-2.52) increased risk of major bleeding compared to the lowest quartile.
conclusionA greater dependence on FXa-mediated activation of FV of TG is associated with increased risk of major bleeding during VKA therapy.
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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.