Factor VII (EC184.108.40.206, blood-coagulation factor VIIa, activated blood coagulation factor VII, formerly known as proconvertin) is one of the proteins that causes blood to clot in the coagulation cascade. It is an enzyme of the serine protease class. A recombinant form of human factor VIIa (eptacog alfa [activated], NovoSeven) has U.S. Food and Drug Administration approval for uncontrolled bleeding in hemophilia patients. It is sometimes used unlicensed in severe uncontrollable bleeding, although there have been safety concerns. A biosimilar form of recombinant activated factor VII (AryoSeven) is also available, but does not play any considerable role in the market.
The main role of factor VII (FVII) is to initiate the process of coagulation in conjunction with tissue factor (TF/factor III). Tissue factor is found on the outside of blood vessels - normally not exposed to the bloodstream. Upon vessel injury, tissue factor is exposed to the blood and circulating factor VII. Once bound to TF, FVII is activated to FVIIa by different proteases, among which are thrombin (factor IIa), factor Xa, IXa, XIIa, and the FVIIa-TF complex itself. The complex of factor VIIa with TF catalyzes the conversion of factor IX and factor X into the active proteases, factor IXa and factor Xa, respectively.
Deficiency is rare (congenital proconvertin deficiency) and inherits recessively. Factor VII deficiency presents as a hemophilia-like bleeding disorder. It is treated with recombinant factor VIIa (NovoSeven or AryoSeven).
It has also been used in the setting of uncontrollable hemorrhage, but its role in this setting is controversial with insufficient evidence to support its use outside of clinical trials. The first report of its use in hemorrhage was in an Israeli soldier with uncontrollable bleeding in 1999. Risks of its use include an increase in arterial thrombosis.
Recombinant human factor VII while initially looking promising in intracerebral hemorrhage failed to show benefit following further study and this is no longer recommended.
^Banner DW, D'Arcy A, Chène C, Winkler FK, Guha A, Konigsberg WH, Nemerson Y, Kirchhofer D (1996). "The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor". Nature380 (6569): 41–6. doi:10.1038/380041a0. PMID8598903.
^Wajima T, Isbister GK, Duffull SB (2009). "A comprehensive model for the humoral coagulation network in humans". Clin Pharmacol Ther86 (3): 290–8. doi:10.1038/clpt.2009.87. PMID19516255.
^ abSimpson E, Lin Y, Stanworth S, Birchall J, Doree C, Hyde C (Mar 14, 2012). "Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia.". Cochrane database of systematic reviews (Online)3: CD005011. doi:10.1002/14651858.CD005011.pub4. PMID22419303.
^Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T (2005). "Recombinant activated factor VII for acute intracerebral hemorrhage". N. Engl. J. Med.352 (8): 777–85. doi:10.1056/NEJMoa042991. PMID15728810.
^Carlsson K, Freskgård PO, Persson E, Carlsson U, Svensson M (Jun 2003). "Probing the interface between factor Xa and tissue factor in the quaternary complex tissue factor-factor VIIa-factor Xa-tissue factor pathway inhibitor". Eur. J. Biochem.270 (12): 2576–82. doi:10.1046/j.1432-1033.2003.03625.x. PMID12787023.
^Zhang E, St Charles R, Tulinsky A (Feb 1999). "Structure of extracellular tissue factor complexed with factor VIIa inhibited with a BPTI mutant". J. Mol. Biol.285 (5): 2089–104. doi:10.1006/jmbi.1998.2452. PMID9925787.
Broze GJ, Majerus PW (1980). "Purification and properties of human coagulation factor VII". J. Biol. Chem.255 (4): 1242–7. PMID7354023.
Versteeg HH, Peppelenbosch MP, Spek CA (2002). "The pleiotropic effects of tissue factor: a possible role for factor VIIa-induced intracellular signalling?". Thromb. Haemost.86 (6): 1353–9. PMID11776298.