ArticleJournal of thrombosis and haemostasis : JTH2010
Bio-distribution of pharmacologically administered recombinant factor VIIa (rFVIIa).
Article in Journal of thrombosis and haemostasis : JTH, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 62 citations in OpenAlex.
- Recombinant factor VIIa: new insights into the mechanism of action through product innovation.Research and practice in thrombosis and haemostasis · 2025Review
- Increased Accumulation and Retention of rhFVIIa (eptacog beta) in Knee Joints of Hemophilia A Mice Compared to Wild-Type Mice.Thrombosis and haemostasis · 2019Article
- A novel luciferase-based assay for the detection of Chimeric Antigen Receptors.Scientific reports · 2019Article
- Heterozygous congenital Factor VII deficiency with the 9729del4 mutation, associated with severe spontaneous intracranial bleeding in an adolescent male.Blood cells, molecules & diseases · 2016Article
- Visualizing cancer and response to therapy in vivo using Cy5.5-labeled factor VIIa and anti-tissue factor antibody.Journal of drug targeting · 2015Article
- FcRn Rescues Recombinant Factor VIII Fc Fusion Protein from a VWF Independent FVIII Clearance Pathway in Mouse Hepatocytes.PloS one · 2015Article
- Pharmacological characteristics of a novel, recombinant fusion protein linking coagulation factor VIIa with albumin (rVIIa-FP).Journal of thrombosis and haemostasis : JTH · 2014Article
- Role of tissue factor in Mycobacterium tuberculosis-induced inflammation and disease pathogenesis.PloS one · 2014Article
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- Mechanisms of anticoagulant and cytoprotective actions of the protein C pathway.Journal of thrombosis and haemostasis : JTH · 2013Review
- Rab GTPases regulate endothelial cell protein C receptor-mediated endocytosis and trafficking of factor VIIa.PloS one · 2013Article
- Endothelial cell protein C receptor-mediated redistribution and tissue-level accumulation of factor VIIa.Journal of thrombosis and haemostasis : JTH · 2012Article
- Factor VIIa binding to endothelial cell protein C receptor: differences between mouse and human systems.Thrombosis and haemostasis · 2012Article
- Endothelial protein C receptor is required for tissue factor ternary complex signaling in the mouse.Journal of thrombosis and haemostasis : JTH · 2011Article
- Pharmacokinetics, pharmacodynamics and safety of recombinant canine FVIIa in a study dosing one haemophilia A and one haemostatically normal dog.Haemophilia : the official journal of the World Federation of Hemophilia · 2011Article
- Redistribution and hemostatic action of recombinant activated factor VII associated with platelets.The American journal of pathology · 2011Article
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- The endothelial protein C receptor supports tissue factor ternary coagulation initiation complex signaling through protease-activated receptors.The Journal of biological chemistry · 2011Article
- Recombinant human factor VIIa (rFVIIa) cleared principally by antithrombin following intravenous administration in hemophilia patients.Journal of thrombosis and haemostasis : JTH · 2011Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundRecent clinical studies suggest that the prophylactic use of recombinant factor VIIa (rFVIIa) markedly reduces the number of bleeding episodes in hemophilic patients with inhibitors. Given the short biological half-life of rFVIIa, it is unclear how rFVIIa could be effective in prophylactic treatment.
objectivesTo examine the extravascular distribution of pharmacologically administered rFVIIa to obtain clues on how rFVIIa could work in prophylaxis.
methodsRecombinant mouse FVIIa tagged with AF488 fluorophore (AF488-FVIIa) was administered into mice via the tail vein. At different time intervals following the administration, mice were exsanguinated and various tissues were collected. The tissue sections were processed for immunohistochemistry to evaluate distribution of rFVIIa.
resultsrFVIIa, immediately following the administration, associated with the endothelium lining of large blood vessels. Within 1 h, rFVIIa bound to endothelial cells was transferred to the perivascular tissue surrounding the blood vessels and thereafter diffused throughout the tissue. In the liver, rFVIIa was localized to sinusoidal capillaries and accumulated in hepatocytes. In bone, rFVIIa was accumulated in the zone of calcified cartilage and some of it was retained there for a week. The common finding of the present study is that rFVIIa in extravascular spaces was mostly localized to regions that contain TF expressing cells.
conclusionsThe present study demonstrates that pharmacologically administered rFVIIa readily associates with the vascular endothelium and subsequently enters into extravascular spaces where it is likely to bind to TF and is retained for extended time periods. This may explain the prolonged pharmacological effect of rFVIIa.
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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.