Factor VII 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 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 is also available, but does not play any considerable role in the market.
Physiology
The main role of factor VII is to initiate the process of coagulation in conjunction with tissue factor. 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 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, 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.
Structure
Factor VII shares a common domain architecture with factors IX and X.
is rare and inherited recessively. It presents as a hemophilia-like bleeding disorder. It is treated with recombinant factor VIIa. Gene therapy approaches for treating FVII deficiency are very promising
Medical uses
, marketed under the trade names AryoSeven and NovoSeven, is used for people with hemophilia 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. However, animal studies have not shown complications as seen in humans, in fact same of the studies show a better prognosis. In the military settings it is used as an off label intervention in complications related to disseminated intravascular coagulation related haemorrhage caused by penetrating trauma. Recombinant human factor VII while initially looking promising in intracerebral hemorrhagefailed to show benefit following further study and this is no longer recommended.
