Factor VII

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Coagulation factor VII (serum prothrombin conversion accelerator)

Anchoring of coagulation factor VIIa (PDB 1dan[1]) to the membrane through its Gla domain
Available structures
PDBOrtholog search: PDBe, RCSB
Identifiers
SymbolsF7; SPCA
External IDsOMIM613878 MGI109325 HomoloGene7710 ChEMBL: 3991 GeneCards: F7 Gene
EC number3.4.21.21
RNA expression pattern
PBB GE F7 207300 s at tn.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez215514068
EnsemblENSG00000057593ENSMUSG00000031443
UniProtP08709P70375
RefSeq (mRNA)NM_000131NM_010172
RefSeq (protein)NP_000122NP_034302
Location (UCSC)Chr 13:
113.76 – 113.77 Mb
Chr 8:
13.03 – 13.04 Mb
PubMed search[1][2]
 
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Coagulation factor VII (serum prothrombin conversion accelerator)

Anchoring of coagulation factor VIIa (PDB 1dan[1]) to the membrane through its Gla domain
Available structures
PDBOrtholog search: PDBe, RCSB
Identifiers
SymbolsF7; SPCA
External IDsOMIM613878 MGI109325 HomoloGene7710 ChEMBL: 3991 GeneCards: F7 Gene
EC number3.4.21.21
RNA expression pattern
PBB GE F7 207300 s at tn.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez215514068
EnsemblENSG00000057593ENSMUSG00000031443
UniProtP08709P70375
RefSeq (mRNA)NM_000131NM_010172
RefSeq (protein)NP_000122NP_034302
Location (UCSC)Chr 13:
113.76 – 113.77 Mb
Chr 8:
13.03 – 13.04 Mb
PubMed search[1][2]

Factor VII (formerly known as proconvertin) is one of the proteins that causes blood to clot in the coagulation cascade. It is an enzyme (EC 3.4.21.21) of the serine protease class. A recombinant form of human factor VIIa (NovoSeven, eptacog alfa [activated]) 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 manufacturing by AryoGen Biopharma and since 2012 is available in the market.

Contents

Physiology

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 most important substrates for FVIIa-TF are Factor X and Factor IX.

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.

Genetics

The gene for factor VII is located on chromosome 13 (13q34).

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).

Medical uses

Recombinant factor VIIa 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,[2] but its role in this setting is controversial with insufficient evidence to support its use outside of clinical trials.[3] The first report of its use in hemorrhage was in an Israeli soldier with uncontrollable bleeding in 1999.[4] Risks of its use include an increase in arterial thrombosis.[3]

Recombinant human factor VII while initially looking promising in intracerebral hemorrhage failed to show benefit following further study and this is no longer recommended.[5][6]

Interactions

Factor VII has been shown to interact with Tissue factor.[7][8]

References

  1. ^ Banner, D. W.; d'Arcy, A.; Chène, C.; Winkler, F. K.; Guha, A.; Konigsberg, W. H.; Nemerson, Y.; Kirchhofer, D. (1996). "The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor". Nature 380 (6569): 41–46. doi:10.1038/380041a0. PMID 8598903. edit
  2. ^ Roberts H, Monroe D, White G (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.
  3. ^ a b Simpson, E; Lin, Y; Stanworth, S; Birchall, J; Doree, C; Hyde, C (2012 Mar 14). "Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia.". Cochrane database of systematic reviews (Online) 3: CD005011. PMID 22419303.
  4. ^ 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.
  5. ^ Mayer S, Brun N, Begtrup K, Broderick J, Davis S, Diringer M, Skolnick B, 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.
  6. ^ Mayer SA, Brun NC, Begtrup K, et al. (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. http://www.nejm.org/doi/full/10.1056/NEJMoa0707534.
  7. ^ Carlsson, Karin; Freskgård Per-Ola, Persson Egon, Carlsson Uno, Svensson Magdalena (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. (Germany) 270 (12): 2576–82. doi:10.1046/j.1432-1033.2003.03625.x. ISSN 0014-2956. PMID 12787023.
  8. ^ 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. (ENGLAND) 285 (5): 2089–104. doi:10.1006/jmbi.1998.2452. ISSN 0022-2836. PMID 9925787.

Further reading

  • Broze GJ Jr, 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.

External links