ArticleJournal of thrombosis and haemostasis : JTH2016
Pharmacological concentrations of recombinant factor VIIa restore hemostasis independent of tissue factor in antibody-induced hemophilia mice.
Article in Journal of thrombosis and haemostasis : JTH, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Recombinant factor VIIa: new insights into the mechanism of action through product innovation.Research and practice in thrombosis and haemostasis · 2025Review
- Cure of Congenital Purpura Fulminans via Expression of Engineered Protein C Through Neonatal Genome Editing in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Coagulation protease-induced extracellular vesicles: their potential effects on coagulation and inflammation.Journal of thrombosis and haemostasis : JTH · 2024Review
- Article
- Oxidative Stress Product, 4-Hydroxy-2-Nonenal, Induces the Release of Tissue Factor-Positive Microvesicles From Perivascular Cells Into Circulation.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- A critical role of endothelial cell protein C receptor in the intestinal homeostasis in experimental colitis.Scientific reports · 2020Article
- Therapeutic doses of recombinant factor VIIa in hemophilia generates thrombin in platelet-dependent and -independent mechanisms.Journal of thrombosis and haemostasis : JTH · 2020Article
- Mouse models of hemostasis.Platelets · 2020Review
- A Molecular Revolution in the Treatment of Hemophilia.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- Limited factor VIIa surface localization requirement of the factor VIIa-induced overall thrombin generation in platelet-rich hemophilia A plasma.Research and practice in thrombosis and haemostasis · 2019Article
- Human platelets express endothelial protein C receptor, which can be utilized to enhance localization of factor VIIa activity.Journal of thrombosis and haemostasis : JTH · 2018Article
- Targeting platelet EPCR for better therapeutic factor VIIa activity.Journal of thrombosis and haemostasis : JTH · 2018Article
- Article
- Engineering of a membrane-triggered activity switch in coagulation factor VIIa.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Factor VIIa interaction with EPCR modulates the hemostatic effect of rFVIIa in hemophilia therapy: Mode of its action.Blood advances · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledESSENTIALS: The role of tissue factor (TF) in recombinant factor VIIa (rFVIIa) therapy in hemophilia is unclear. An acquired mouse hemophilia model with very low or normal levels of human TF was used in the study. rFVIIa is equally effective in correcting the bleeding in mice expressing low or normal levels of TF. Pharmacological doses of rFVIIa restore hemostasis in hemophilia independent of TF. SUMMARY:
backgroundRecombinant factor VIIa (rFVIIa) has been used widely for treating hemophilia patients with inhibitory autoantibodies against factor VIII or IX. Its mechanism of action is not entirely known. A majority of in vitro studies suggested that pharmacological concentrations of rFVIIa restore hemostasis in hemophilia in a phospholipid-dependent manner, independent of tissue factor (TF). However, a few studies suggested that a TF-dependent mechanism has a primary role in correction of bleeding by rFVIIa in hemophilia patients. Here, we investigated the potential contribution of TF in rFVIIa-induced hemostasis in hemophilia employing a model system of FVIII antibody-induced hemophilia in TF transgenic mice.
methodsMice expressing low levels of human TF (LTF mice), mice expressing relatively high levels of human TF (HTF mice) and wild-type mice (WT mice) had neutralizing anti-FVIII antibodies administered in order to induce hemophilia in these mice. The mice were then treated with varying concentrations of rFVIIa. rFVIIa-induced hemostasis was evaluated with the saphenous vein bleeding model.
resultsAdministration of FVIII inhibitory antibodies induced the hemophilic bleeding phenotype in all three genotypes. rFVIIa administration rescued the bleeding phenotype in all three genotypes. No significant differences were observed in rFVIIa-induced correction of bleeding between LTF and HTF mice that had FVIII antibodies administered.
conclusionsOur results provide strong evidence supporting the suggestion that the hemostatic effect of pharmacological doses of rFVIIa stems from a TF-independent mechanism.
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