Recombinant human factor VIIa (rFVIIa) in hemophilia: mode of action and evidence to date

Recombinant activated factor VII (rFVIIa) is a bypassing agent widely used both in the treatment and prevention of hemorrhagic complications due to hemophilia with inhibitor. In such cases, antihemophilic factors cannot be used. The normal physiology of factor VII/ factor VIIa (FVII/FVIIa) in the he...

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Bibliographic Details
Published in:Therapeutic Advances in Hematology 2017-12, Vol.8 (12), p.345-352
Main Authors: Giansily-Blaizot, Muriel, Schved, Jean-François
Format: Article
Language:English
Subjects:
Coagulation
Evidence-based medicine
Hemophilia
Inhibitor drugs
Pharmacodynamics
Reviews
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Summary:Recombinant activated factor VII (rFVIIa) is a bypassing agent widely used both in the treatment and prevention of hemorrhagic complications due to hemophilia with inhibitor. In such cases, antihemophilic factors cannot be used. The normal physiology of factor VII/ factor VIIa (FVII/FVIIa) in the hemostatic process requires the presence of tissue factor (TF) that links to FVII leading to a FVIIa-TF complex which activates both factor X and factor IX. The therapeutic use of rFVIIa requires high amount of FVIIa. Some studies demonstrate that FVIIa at high doses still requires tissue factor for function, whereas others suggest that FVIIa activates FX directly on the platelet surface, in a TF-independent manner. In the present article, we discuss the arguments supporting both TF-dependent and TF-independent modes of action. Finally, the coexistence of both TF-dependent and TF-independent mechanisms cannot be excluded.
ISSN:2040-6207
2040-6215
DOI:10.1177/2040620717737701