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{{Infobox_gene}}
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'''Factor VII''' ({{EC number|3.4.21.21}}, ''blood-coagulation factor VIIa'', ''activated blood coagulation factor VII'', formerly known as '''proconvertin''') is one of the [[protein]]s that causes blood to clot in the [[coagulation|coagulation cascade]]. It is an [[enzyme]] of the [[serine protease]] class. A [[Recombinant DNA|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.
| require_manual_inspection = no
| update_protein_box = yes
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| update_citations = yes
}}
{{GNF_Protein_box
| image = 1dan opm.gif
| image_source =  Anchoring of coagulation factor VIIa to the mebrane through its [[Gla domain]]
| Name = Coagulation factor VII (serum prothrombin conversion accelerator)
| HGNCid = 3544
| Symbol = F7
| AltSymbols =;
| OMIM = 227500
| ECnumber = 
| Homologene = 7710
| MGIid = 109325
| GeneAtlas_image1 = PBB_GE_F7_207300_s_at_tn.png
| Function = {{GNF_GO|id=GO:0003802 |text = coagulation factor VIIa activity}} {{GNF_GO|id=GO:0004252 |text = serine-type endopeptidase activity}} {{GNF_GO|id=GO:0005509 |text = calcium ion binding}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}}
| Process = {{GNF_GO|id=GO:0006508 |text = proteolysis}} {{GNF_GO|id=GO:0007596 |text = blood coagulation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 2155
    | Hs_Ensembl = ENSG00000057593
    | Hs_RefseqProtein = NP_000122
    | Hs_RefseqmRNA = NM_000131
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 13
    | Hs_GenLoc_start = 112808106
    | Hs_GenLoc_end = 112822996
    | Hs_Uniprot = P08709
    | Mm_EntrezGene = 14068
    | Mm_Ensembl = ENSMUSG00000031443
    | Mm_RefseqmRNA = NM_010172
    | Mm_RefseqProtein = NP_034302
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 8
    | Mm_GenLoc_start = 13026011
    | Mm_GenLoc_end = 13035782
    | Mm_Uniprot = Q542C2
  }}
}}
{{SI}}
{{CMG}}


== Physiology ==


The main role of factor VII (FVII) is to initiate the process of coagulation in conjunction with [[tissue factor]] (TF/factor VII). 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.<ref>{{cite journal | vauthors = Wajima T, Isbister GK, Duffull SB | title = A comprehensive model for the humoral coagulation network in humans | journal = Clinical Pharmacology and Therapeutics | volume = 86 | issue = 3 | pages = 290–8 | date = September 2009 | pmid = 19516255 | doi = 10.1038/clpt.2009.87 }}</ref>


'''Factor VII''' (formerly known as '''proconvertin''') is one of the central [[protein]]s in the [[coagulation|coagulation cascade]]. It is an [[enzyme]] ({{EC number|3.4.21.21}}) of the [[serine protease]] class.
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 [[anticoagulant]]s decreases hepatic synthesis of FVII.


==Physiology==
==Structure==
The main role of factor VII (FVII) is to initiate the process of coagulation in conjunction with [[tissue factor]] (TF). 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), activated factor X and the FVIIa-TF complex itself. The most important substrates for FVIIa-TF are [[Factor X]] and [[Factor IX]].
{{See also|Factor_IX#Domain_architecture}}
Factor VII shares a common domain architecture with factors [[factor IX|IX]] and [[factor X|X]].


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 [[anticoagulant]]s impairs its function.
== Genetics ==


==Genetics==
The [[gene]] for factor VII is located on [[chromosome 13]] (13q34).


The [[gene]] for factor VII is located on [[chromosome]] 13 (13q34).
== Role in disease ==
{{main|Factor VII deficiency}}
[[Factor VII deficiency]] (congenital proconvertin deficiency) is rare and inherited recessively.  It presents as a hemophilia-like bleeding disorder.  It is treated with recombinant factor VIIa (NovoSeven or [[AryoSeven]]).


==Role in disease==
== Medical uses ==


Deficiency is rare (congenital proconvertin deficiency) and inherits recessively.
[[Recombinant factor VIIa]], marketed under the trade names ''AryoSeven'' and ''NovoSeven'', is used for people with [[hemophilia]] (with [[Factor VIII]] or [[Factor IX|IX]] deficiency) who have developed antibodies against replacement coagulation factor.


==Therapeutic use==
It has also been used in the setting of uncontrollable hemorrhage,<ref>{{cite journal | vauthors = Roberts HR, Monroe DM, White GC | title = The use of recombinant factor VIIa in the treatment of bleeding disorders | journal = Blood | volume = 104 | issue = 13 | pages = 3858–64 | date = December 2004 | pmid = 15328151 | doi = 10.1182/blood-2004-06-2223 }}</ref><ref>[https://www.mcdonaldworley.com/xarelto-lawsuit.php Uncontrolled Bleeding and Injury Lawsuit Claims]</ref> but its role in this setting is controversial with insufficient evidence to support its use outside of clinical trials.<ref name=Cochrane2012>{{cite journal | vauthors = Simpson E, Lin Y, Stanworth S, Birchall J, Doree C, Hyde C | title = Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia | journal = The Cochrane Database of Systematic Reviews | volume = 3 | issue = 3 | pages = CD005011 | date = March 2012 | pmid = 22419303 | doi = 10.1002/14651858.CD005011.pub4 }}</ref> The first report of its use in hemorrhage was in an [[Israel]]i soldier with uncontrollable bleeding in 1999.<ref>{{cite journal | vauthors = Kenet G, Walden R, Eldad A, Martinowitz U | title = Treatment of traumatic bleeding with recombinant factor VIIa | journal = Lancet | volume = 354 | issue = 9193 | pages = 1879 | date = November 1999 | pmid = 10584732 | doi = 10.1016/S0140-6736(99)05155-7 }}</ref> Risks of its use include an increase in arterial thrombosis.<ref name=Cochrane2012/>


[[Recombinant]] human factor VIIa (NovoSeven®, eptacog alfa [activated], ATC code B02BD08) has been introduced for use in uncontrollable [[hemorrhage|bleeding]] in [[hemophilia]] patients (with [[Factor VIII]] or [[Factor IX|IX]] deficiency) who have developed inhibitors against replacement coagulation factor.
Recombinant human factor VII while initially looking promising in [[intracerebral hemorrhage]] failed to show benefit following further study and this is no longer recommended.<ref>{{cite journal | vauthors = Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T | title = Recombinant activated factor VII for acute intracerebral hemorrhage | journal = The New England Journal of Medicine | volume = 352 | issue = 8 | pages = 777–85 | date = February 2005 | pmid = 15728810 | doi = 10.1056/NEJMoa042991 }}</ref><ref>{{cite journal | vauthors = Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T | title = Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage | journal = The New England Journal of Medicine | volume = 358 | issue = 20 | pages = 2127–37 | date = May 2008 | pmid = 18480205 | doi = 10.1056/NEJMoa0707534 | url = http://www.nejm.org/doi/full/10.1056/NEJMoa0707534 }}</ref>


It is being increasingly used in uncontrollable hemorrhage.<ref>{{cite journal |author=Roberts H, Monroe D, White G |title=The use of recombinant factor VIIa in the treatment of bleeding disorders |journal=Blood |volume=104 |issue=13 |pages=3858-64 |year=2004 |pmid=15328151}}</ref> The first report of its use was in an Israeli soldier with uncontrollable bleeding in 1999.<ref>{{cite journal |author=Kenet G, Walden R, Eldad A, Martinowitz U |title=Treatment of traumatic bleeding with recombinant factor VIIa |journal=Lancet |volume=354 |issue=9193 |pages=1879 |year=1999 |pmid=10584732}}</ref> The rationale for its use in hemorrhage is, that it will only induce coagulation in those sites where tissue factor (TF) is also present. Still, O'Connell ''et al'' report an increased risk of [[deep vein thrombosis]], [[pulmonary embolism]] and [[myocardial infarction]] in association with the use of rhFVIIa.<ref>{{cite journal |author=O'Connell K, Wood J, Wise R, Lozier J, Braun M |title=Thromboembolic adverse events after use of recombinant human coagulation factor VIIa |journal=JAMA |volume=295 |issue=3 |pages=293-8 |year=2006 |pmid=16418464}}</ref>
== Interactions ==


According to a 2005 study, recombinant human factor VII improves outcomes in acute [[intracerebral hemorrhage]].<ref>{{cite journal |author=Mayer S, Brun N, Begtrup K, Broderick J, Davis S, Diringer M, Skolnick B, Steiner T |title=Recombinant activated factor VII for acute intracerebral hemorrhage |journal=N. Engl. J. Med. |volume=352 |issue=8 |pages=777-85 |year=2005 |pmid=15728810}}</ref>
Factor VII has been shown to [[Protein-protein interaction|interact]] with [[tissue factor]].Also reacts with protein kinase C.<ref name=pmid12787023>{{cite journal | vauthors = Carlsson K, Freskgård PO, Persson E, Carlsson U, Svensson M | title = Probing the interface between factor Xa and tissue factor in the quaternary complex tissue factor-factor VIIa-factor Xa-tissue factor pathway inhibitor | journal = European Journal of Biochemistry | volume = 270 | issue = 12 | pages = 2576–82 | date = June 2003 | pmid = 12787023 | doi = 10.1046/j.1432-1033.2003.03625.x }}</ref><ref name=pmid9925787>{{cite journal | vauthors = Zhang E, St Charles R, Tulinsky A | title = Structure of extracellular tissue factor complexed with factor VIIa inhibited with a BPTI mutant | journal = Journal of Molecular Biology | volume = 285 | issue = 5 | pages = 2089–104 | date = February 1999 | pmid = 9925787 | doi = 10.1006/jmbi.1998.2452 }}</ref>
{{-}}
== References ==
{{Reflist|33em}}


==References==
== Further reading ==
{{Reflist}}
{{refbegin|33em}}
 
* {{cite journal | vauthors = Broze GJ, Majerus PW | title = Purification and properties of human coagulation factor VII | journal = The Journal of Biological Chemistry | volume = 255 | issue = 4 | pages = 1242–7 | date = February 1980 | pmid = 7354023 }}
==External links==
* {{cite journal | vauthors = Versteeg HH, Peppelenbosch MP, Spek CA | title = The pleiotropic effects of tissue factor: a possible role for factor VIIa-induced intracellular signalling? | journal = Thrombosis and Haemostasis | volume = 86 | issue = 6 | pages = 1353–9 | date = December 2001 | pmid = 11776298 | doi =  }}
*[http://www.novoseven-us.com Web site for novoseven-us.com]
* {{cite journal | vauthors = Golino P | title = The inhibitors of the tissue factor:factor VII pathway | journal = Thrombosis Research | volume = 106 | issue = 3 | pages = V257-65 | date = May 2002 | pmid = 12356487 | doi = 10.1016/S0049-3848(02)00079-8 }}
{{refend}}


==Further reading==
== External links ==
{{refbegin | 2}}
* [http://www.novosevenrt.com/ Official website]
{{PBB_Further_reading
* The [[MEROPS]] online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=S01.215 S01.215]
| citations =  
* CHES - Comprehensive Health Education Services LLC - Factor VII treatment and awareness [http://www.comphealthed.com/]
*{{cite journal  | author=Versteeg HH, Peppelenbosch MP, Spek CA |title=The pleiotropic effects of tissue factor: a possible role for factor VIIa-induced intracellular signalling? |journal=Thromb. Haemost. |volume=86 |issue= 6 |pages= 1353-9 |year= 2002 |pmid= 11776298 |doi=  }}
*{{cite journal  | author=Golino P |title=The inhibitors of the tissue factor:factor VII pathway. |journal=Thromb. Res. |volume=106 |issue= 3 |pages= V257-65 |year= 2003 |pmid= 12356487 |doi=  }}
}}
{{refend}}


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[[Category:Coagulation system]]
[[Category:Coagulation system]]
[[Category:EC 3.4.21]]
[[Category:EC 3.4.21]]
[[Category:Peripheral membrane proteins]]
[[Category:Peripheral membrane proteins]]
[[Category:Hematology]]
[[ca:Factor VII]]
[[de:Proconvertin]]
[[pl:Prokonwertyna]]
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Revision as of 15:51, 16 October 2017

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Factor VII (EC 3.4.21.21, 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.

Physiology

The main role of factor VII (FVII) is to initiate the process of coagulation in conjunction with tissue factor (TF/factor VII). 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.[1]

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.

Structure

See also: Factor_IX § Domain_architecture

Factor VII shares a common domain architecture with factors IX and X.

Genetics

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

Role in disease

Main article: Factor VII deficiency

Factor VII deficiency (congenital proconvertin deficiency) is rare and inherited recessively. It presents as a hemophilia-like bleeding disorder. It is treated with recombinant factor VIIa (NovoSeven or AryoSeven).

Medical uses

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 antibodies against replacement coagulation factor.

It has also been used in the setting of uncontrollable hemorrhage,[2][3] but its role in this setting is controversial with insufficient evidence to support its use outside of clinical trials.[4] The first report of its use in hemorrhage was in an Israeli soldier with uncontrollable bleeding in 1999.[5] Risks of its use include an increase in arterial thrombosis.[4]

Recombinant human factor VII while initially looking promising in intracerebral hemorrhage failed to show benefit following further study and this is no longer recommended.[6][7]

Interactions

Factor VII has been shown to interact with tissue factor.Also reacts with protein kinase C.[8][9]

References

  1. ↑ Wajima T, Isbister GK, Duffull SB (September 2009). "A comprehensive model for the humoral coagulation network in humans". Clinical Pharmacology and Therapeutics. 86 (3): 290–8. doi:10.1038/clpt.2009.87. PMID 19516255.
  2. ↑ Roberts HR, Monroe DM, White GC (December 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. ↑ Uncontrolled Bleeding and Injury Lawsuit Claims
  4. ↑ 4.0 4.1 Simpson E, Lin Y, Stanworth S, Birchall J, Doree C, Hyde C (March 2012). "Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia". The Cochrane Database of Systematic Reviews. 3 (3): CD005011. doi:10.1002/14651858.CD005011.pub4. PMID 22419303.
  5. ↑ Kenet G, Walden R, Eldad A, Martinowitz U (November 1999). "Treatment of traumatic bleeding with recombinant factor VIIa". Lancet. 354 (9193): 1879. doi:10.1016/S0140-6736(99)05155-7. PMID 10584732.
  6. ↑ Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T (February 2005). "Recombinant activated factor VII for acute intracerebral hemorrhage". The New England Journal of Medicine. 352 (8): 777–85. doi:10.1056/NEJMoa042991. PMID 15728810.
  7. ↑ 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". The New England Journal of Medicine. 358 (20): 2127–37. doi:10.1056/NEJMoa0707534. PMID 18480205.
  8. ↑ Carlsson K, Freskgård PO, Persson E, Carlsson U, Svensson M (June 2003). "Probing the interface between factor Xa and tissue factor in the quaternary complex tissue factor-factor VIIa-factor Xa-tissue factor pathway inhibitor". European Journal of Biochemistry. 270 (12): 2576–82. doi:10.1046/j.1432-1033.2003.03625.x. PMID 12787023.
  9. ↑ Zhang E, St Charles R, Tulinsky A (February 1999). "Structure of extracellular tissue factor complexed with factor VIIa inhibited with a BPTI mutant". Journal of Molecular Biology. 285 (5): 2089–104. doi:10.1006/jmbi.1998.2452. PMID 9925787.

Further reading

  • Broze GJ, Majerus PW (February 1980). "Purification and properties of human coagulation factor VII". The Journal of Biological Chemistry. 255 (4): 1242–7. PMID 7354023.
  • Versteeg HH, Peppelenbosch MP, Spek CA (December 2001). "The pleiotropic effects of tissue factor: a possible role for factor VIIa-induced intracellular signalling?". Thrombosis and Haemostasis. 86 (6): 1353–9. PMID 11776298.
  • Golino P (May 2002). "The inhibitors of the tissue factor:factor VII pathway". Thrombosis Research. 106 (3): V257–65. doi:10.1016/S0049-3848(02)00079-8. PMID 12356487.

External links

  • Official website
  • The MEROPS online database for peptidases and their inhibitors: S01.215
  • CHES - Comprehensive Health Education Services LLC - Factor VII treatment and awareness [2]
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