DiaPharma Group, Inc.

Factor VII (FVII, also known as Stable Factor and Proconvertin) is a vitamin K-dependent glycoprotein produced in the liver. Plasma concentration of FVII is normally ~0.5 micrograms/milliliters (10 nM) in plasma. A deficiency of FVII is associated with bleeding in a clinical pattern similar to hemophilia, but is inherited as an autosomal recessive trait. The deficiency can be characterized by a quantitative (low activity and low antigen) or a qualitative (low activity and normal antigen) defect in FVII function. In its zymogen form FVII is a single chain molecule of ~50 kDa. It contains two EGF-like domains and an amino-terminal domain containing 10 gamma-carboxyglutamic acid (Gla) residues. These Gla residues allow FVII to bind divalent metal ions and participate in calcium-dependent binding interactions. FVII and activated FVII (FVIIa) bind to tissue factor exposed at the site of vascular injury. FIXa, FXa or FVIIa rapidly activate tissue factor-bound FVII to FVIIa in the presence of calcium and phospholipid. Thrombin and FXIIa are able to activate FVII in the fluid phase in the absence of cofactors. The activation of the single chain zymogen FVII occurs by proteolysis after residue Arg¹⁵², resulting in a two-chain active serine protease consisting of a 30 kDa heavy chain and a 18 kDa light chain. In complex with tissue factor, phospholipid and calcium, FVIIa is able to activate FX and FIX. Free FVIIa in plasma is remarkably stable, but the activity of FVIIa/TF complex is regulated by Tissue Factor Pathway Inhibitor (TFPI) in the presence of FXa, and also by Antithrombin (ATIII) in the presence of heparin.