|Coagulation factor VII (serum prothrombin conversion accelerator)|
Anchoring of coagulation factor VIIa (PDB ) to the membrane through its Gla domain
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|RNA expression pattern|
Factor VII (EC 184.108.40.206, 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.
The action of the factor is impeded by tissue factor pathway inhibitor (TFPI), which is released almost immediately after initiation of coagulation. Factor VII is vitamin K dependent; it is produced in the liver. Use of warfarin or similar anticoagulants decreases hepatic synthesis of FVII.
Role in disease
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).
Recombinant factor VIIa, marketed under the trade names AryoSeven and NovoSeven, is used for people with hemophilia (with Factor VIII or IX deficiency) who have developed inhibitors against replacement coagulation factor.
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.
- 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". Nature 380 (6569): 41–6. doi:10.1038/380041a0. PMID 8598903.
- Wajima T, Isbister GK, Duffull SB (2009). "A comprehensive model for the humoral coagulation network in humans". Clin Pharmacol Ther 86 (3): 290–8. doi:10.1038/clpt.2009.87. PMID 19516255.
- Roberts HR, Monroe DM, White GC (2004). "The use of recombinant factor VIIa in the treatment of bleeding disorders". Blood 104 (13): 3858–64. doi:10.1182/blood-2004-06-2223. PMID 15328151.
- Simpson 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. PMID 22419303.
- Kenet G, Walden R, Eldad A, Martinowitz U (1999). "Treatment of traumatic bleeding with recombinant factor VIIa". Lancet 354 (9193): 1879. doi:10.1016/S0140-6736(99)05155-7. PMID 10584732.
- 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. PMID 15728810.
- Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T (May 2008). "Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage". N. Engl. J. Med. 358 (20): 2127–37. doi:10.1056/NEJMoa0707534. PMID 18480205.
- 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. PMID 12787023.
- 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. PMID 9925787.
- Broze GJ, Majerus PW (1980). "Purification and properties of human coagulation factor VII". J. Biol. Chem. 255 (4): 1242–7. PMID 7354023.
- 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. PMID 11776298.
- Golino P (2003). "The inhibitors of the tissue factor:factor VII pathway". Thromb. Res. 106 (3): V257–65. doi:10.1016/S0049-3848(02)00079-8. PMID 12356487.