ArticleBlood2012
Unifying the mechanism of recombinant FVIIa action: dose dependence is regulated differently by tissue factor and phospholipids.
Article in Blood, 2012. 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.
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Who cites it
18 citing papers in PubMed, 56 citations in OpenAlex.
- The procoagulant effect described in preparations of plasma-derived β2-glycoprotein I (β2GPI) is mediated by contamination with factor XIa.Journal of thrombosis and thrombolysis · 2026Article
- Recombinant factor VIIa: new insights into the mechanism of action through product innovation.Research and practice in thrombosis and haemostasis · 2025Review
- Impacts of the COVID-19 pandemic on pediatric and adult patients with hemophilia.Annals of hematology · 2025Article
- Coagulation protease-induced extracellular vesicles: their potential effects on coagulation and inflammation.Journal of thrombosis and haemostasis : JTH · 2024Review
- A Review of Quantitative Systems Pharmacology Models of the Coagulation Cascade: Opportunities for Improved Usability.Pharmaceutics · 2023Review
- Exploratory in vitro evaluation of thrombin generation of eptacog beta (recombinant human fviia) and emicizumab in congenital haemophilia A plasma.Haemophilia : the official journal of the World Federation of Hemophilia · 2021Article
- Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice.Thrombosis journal · 2020Article
- Therapeutic doses of recombinant factor VIIa in hemophilia generates thrombin in platelet-dependent and -independent mechanisms.Journal of thrombosis and haemostasis : JTH · 2020Article
- The evolution of factor VIIa in the treatment of bleeding in haemophilia with inhibitors.Haemophilia : the official journal of the World Federation of Hemophilia · 2019Review
- Venous Thrombosis in Acquired Hemophilia: The Complex Management of Competing Pathologies.TH open : companion journal to thrombosis and haemostasis · 2019Article
- Mitigation of T-cell dependent immunogenicity by reengineering factor VIIa analogue.Blood advances · 2019Article
- Neonatal thrombocytopenia: Thrombin generation in presence of reduced platelet counts and effects of rFVIIa in cord blood.Scientific reports · 2019Observational
- Recombinant human factor VIIa (rFVIIa) in hemophilia: mode of action and evidence to date.Therapeutic advances in hematology · 2017Review
- Recombinant factor VIIa addition to haemophilic blood perfused over collagen/tissue factor can sufficiently bypass the factor IXa/VIIIa defect to rescue fibrin generation.Haemophilia : the official journal of the World Federation of Hemophilia · 2017Article
- Pharmacological concentrations of recombinant factor VIIa restore hemostasis independent of tissue factor in antibody-induced hemophilia mice.Journal of thrombosis and haemostasis : JTH · 2016Article
- Characterization of procoagulant extracellular vesicles and platelet membrane disintegration in DMSO-cryopreserved platelets.Journal of extracellular vesicles · 2016Article
- Article
- Correction of microplate location effects improves performance of the thrombin generation test.Thrombosis journal · 2013Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recombinant factor VIIa (rFVIIa) is used for treatment of hemophilia patients with inhibitors, as well for off-label treatment of severe bleeding in trauma and surgery. Effective bleeding control requires supraphysiological doses of rFVIIa, posing both high expense and uncertain thrombotic risk. Two major competing theories offer different explanations for the supraphysiological rFVIIa dosing requirement: (1) the need to overcome competition between FVIIa and FVII zymogen for tissue factor (TF) binding, and (2) a high-dose-requiring phospholipid-related pathway of FVIIa action. In the present study, we found experimental conditions in which both mechanisms contribute simultaneously and independently to rFVIIa-driven thrombin generation in FVII-deficient human plasma. From mathematical simulations of our model of FX activation, which were confirmed by thrombin-generation experiments, we conclude that the action of rFVIIa at pharmacologic doses is dominated by the TF-dependent pathway with a minor contribution from a phospholipid-dependent mechanism. We established a dose-response curve for rFVIIa that is useful to explain dosing strategies. In the present study, we present a pathway to reconcile the 2 major mechanisms of rFVIIa action, a necessary step to understanding future dose optimization and evaluation of new rFVIIa analogs currently under development.
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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.