Factor VII

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 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, which was discovered around 1950, is vitamin K-dependent and produced in the liver. Use of warfarin or similar anticoagulants decreases hepatic synthesis of FVII.

A coagulation enzyme cascade may begin with a few molecules of factor XII and culminate in the activation of millions of times more fibrin molecules.

Structure

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). Gene therapy approaches for treating FVII deficiency are very promising ()

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, 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.

Interactions

Factor VII has been shown to interact with tissue factor and endothelial protein C receptor.

References

References

1. (January 2019). "Eptacog beta: a novel recombinant human factor VIIa for the treatment of hemophilia A and B with inhibitors". Expert Review of Hematology.
2. (September 2009). "A comprehensive model for the humoral coagulation network in humans". Clinical Pharmacology and Therapeutics.
3. (April 2013). "Ultrasensitive response motifs: basic amplifiers in molecular signalling networks". Open Biology.
4. (February 2016). "Sustained correction of FVII deficiency in dogs using AAV-mediated expression of zymogen FVII". Blood.
5. (December 2004). "The use of recombinant factor VIIa in the treatment of bleeding disorders". Blood.
6. "Uncontrolled Bleeding and Injury Lawsuit Claims".
7. (March 2012). "Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia". The Cochrane Database of Systematic Reviews.
8. (November 1999). "Treatment of traumatic bleeding with recombinant factor VIIa". Lancet.
9. (December 2007). "UK defence medical services guidance for the use of recombinant factor VIIa (rFVIIa) in the deployed military setting". Journal of the Royal Army Medical Corps.
10. (February 2005). "Recombinant activated factor VII for acute intracerebral hemorrhage". The New England Journal of Medicine.
11. (May 2008). "Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage". The New England Journal of Medicine.
12. (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.
13. (February 1999). "Structure of extracellular tissue factor complexed with factor VIIa inhibited with a BPTI mutant". Journal of Molecular Biology.