Factor VII clotting activity

Factor VII is a single-chain, vitamin K-dependent glycoprotein of molecular weight 47 000–50 0001–5. Its plasma concentration is about 250–700ng/ml (5–15nmol/L). The complex of the zymogen factor VII with tissue thromboplastin and Ca2+ has been proposed as an efficient activator of factor X7,8 Factor VII can be converted to the two-chain α-VIIa by hydrolysis of an Arg-Ile bond by factors Xa, IXa, XIIa or thrombin1,2,6,10 The coagulant activity of α-VIIa is 100-fold increased compared to single-chain factor VII8. Further cleavage of α-VIIa at the heavy chain destroys coagulant activity9. The complex of factor VII/VIIa with tissue factor also activates factor IX to IXa11,12. Some authors13,14 virtually deny any physiologically relevant enzymatic activity to the complex of tissue factor with non-activated factor VII. Their concept of extrinsic activation requires the presence of factor VIIa in trace amounts. Factor Xa will then be generated by the factor VIIa/tissue factor complex (and also by reactions of the intrinsic coagulation pathway) and activate the thromboplastin bound zymogen factor VII to VIIa. This potent amplification loop is subjected to complex regulation mechanisms15.