ArticleJournal of thrombosis and haemostasis : JTH2012
Endothelial cell protein C receptor-mediated redistribution and tissue-level accumulation of factor VIIa.
Article in Journal of thrombosis and haemostasis : JTH, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- The safety of activated eptacog beta in the management of bleeding episodes and perioperative haemostasis in adult and paediatric haemophilia patients with inhibitors.Haemophilia : the official journal of the World Federation of Hemophilia · 2021Trial
- The effects of recombinant human activated factor VII and tranexamic acid on traumatic bleeding and mortality in mice.Research and practice in thrombosis and haemostasis · 2026Article
- Recombinant factor VIIa: new insights into the mechanism of action through product innovation.Research and practice in thrombosis and haemostasis · 2025Review
- Endothelial Protein C Receptor and Its Impact on Rheumatic Disease.Journal of clinical medicine · 2024Review
- Pleiotropic actions of factor Xa inhibition in cardiovascular prevention: mechanistic insights and implications for anti-thrombotic treatment.Cardiovascular research · 2021Review
- 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
- Increased Accumulation and Retention of rhFVIIa (eptacog beta) in Knee Joints of Hemophilia A Mice Compared to Wild-Type Mice.Thrombosis and haemostasis · 2019Article
- Gene-based FVIIa prophylaxis modulates the spontaneous bleeding phenotype of hemophilia A rats.Blood advances · 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
- The role of recombinant activated factor VII in the haematological management of elective orthopaedic surgery in haemophilia A patients with inhibitors.Blood transfusion = Trasfusione del sangue · 2017Review
- Gene Delivery of Activated Factor VII Using Alternative Adeno-Associated Virus Serotype Improves Hemostasis in Hemophiliac Mice with FVIII Inhibitors and Adeno-Associated Virus Neutralizing Antibodies.Human gene therapy · 2017Article
- Heterozygous congenital Factor VII deficiency with the 9729del4 mutation, associated with severe spontaneous intracranial bleeding in an adolescent male.Blood cells, molecules & diseases · 2016Article
- Sustained correction of FVII deficiency in dogs using AAV-mediated expression of zymogen FVII.Blood · 2016Article
- Review
- The endothelial protein C receptor enhances hemostasis of FVIIa administration in hemophilic mice in vivo.Blood · 2014Article
- Factor VIIa binding to endothelial cell protein C receptor protects vascular barrier integrity in vivo.Journal of thrombosis and haemostasis : JTH · 2014Article
- Article
- Rab GTPases regulate endothelial cell protein C receptor-mediated endocytosis and trafficking of factor VIIa.PloS one · 2013Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundRecent studies show that activated factor VII (FVIIa) binds to the endothelial cell protein C receptor (EPCR) on the vascular endothelium; however, the importance of this interaction in hemostasis or pathophysiology is unknown.
objectiveThe aim of the present study was to investigate the role of the FVIIa interaction with EPCR on the endothelium in mediating FVIIa transport from the circulation to extravascular tissues.
methodsWild-type, EPCR-deficient or ECPR-over-expressing mice were injected with human recombinant (r)FVIIa (120 μg kg(-1) body weight) via the tail vein. At varying time intervals after rFVIIa administration, blood and various tissues were collected to measure FVIIa antigen and activity levels. Tissue sections were analyzed by immunohistochemistry for FVIIa and EPCR.
resultsThe data reveal that, after intravenous (i.v.) injection, rFVIIa rapidly disappears from the blood and associates with the endothelium in an EPCR-dependent manner. Immunohistochemical analyses revealed that the association of FVIIa with the endothelium was maximal at 30 min and thereafter progressively declined. The FVIIa association with the endothelium was undetectable at time points exceeding 24 h post-FVIIa administration. The levels of rFVIIa accumulated in tissue correlate with expression levels of EPCR in mice and FVIIa associated with tissues remained functionally active for periods of at least 7 days.
conclusionsThe observation that an EPCR-dependent association of FVIIa with the endothelium is most pronounced soon after rFVIIa administration and subsequently declines temporally, combined with the retention of functionally active FVIIa in tissue homogenates for extended periods, indicates that FVIIa binding to EPCR on the endothelium facilitates the transport of FVIIa from circulation to extravascular tissues where TF resides.
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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.