Factor VII

Factor VII (formerly known as proconvertin) is one of the central proteins in the coagulation cascade. It is an enzyme (EC 3.4.21.21) of the serine protease class.

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Physiology

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.

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 impairs its function.

Genetics

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

Role in disease

Deficiency is rare (congenital proconvertin deficiency) and inherits recessively.

Therapeutic use

Recombinant human factor VIIa (NovoSeven®, eptacog alfa [activated], ATC code B02BD08) has been introduced for use in uncontrollable bleeding in hemophilia patients (with Factor VIII or IX deficiency) who have developed inhibitors against replacement coagulation factor.

It is being increasingly used in uncontrollable hemorrhage.^[1] The first report of its use was in an Israeli soldier with uncontrollable bleeding in 1999.^[2] 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.^[3]

According to a 2005 study, recombinant human factor VII improves outcomes in acute intracerebral hemorrhage.^[4]

References

1. ^ Roberts H, Monroe D, White G (2004). "The use of recombinant factor VIIa in the treatment of bleeding disorders". Blood 104 (13): 3858-64. PMID 15328151.
2. ^ Kenet G, Walden R, Eldad A, Martinowitz U (1999). "Treatment of traumatic bleeding with recombinant factor VIIa". Lancet 354 (9193): 1879. PMID 10584732.
3. ^ O'Connell K, Wood J, Wise R, Lozier J, Braun M (2006). "Thromboembolic adverse events after use of recombinant human coagulation factor VIIa". JAMA 295 (3): 293-8. PMID 16418464.
4. ^ 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. PMID 15728810.

Further reading