Isolation and Expression of cDNAs Encoding Human Factor VII

Two alternative pathways exist for the activation of factor X, a step required to convert prothrombin to thrombin in the later stages of the coagulation cascade. In the intrinsic pathway of blood coagulation, a series of protease-mediated activations ultimately generates factor IXa (see Fig. 1). This protein, coupled with factor VIIIa, produces factor Xa from factor X by cleavage of a glycopeptide from the heavy-chain amino terminus (Davie et al. 1979). An identical proteolysis is effected by factor VIIa and tissue factor in the extrinsic pathway of blood coagulation. Tissue factor, a membrane-bound protein, normally does not circulate in plasma. Upon vessel disruption, however, it can complex with factor VIIa to catalyze the factor X activation in a Ca++- and phospholipid-dependent manner (Østerud and Rapaport 1977).