The Use of Recombinant Factor VII in Management of Bleeding Disorders

Abstract

ecombinant FVIIa is a vitamin-K dependent glycoprotein that is structurally similar to human plasma-derived factor VIIa. No human serum or proteins are used in the production of rFVIIa. It is manufactured by cloning of the human factor VII gene and is expressed in baby hamster kidney cells, then cultured in bovine albumin. This process eliminates the risk of human blood-borne infection. Recombinant FVIIa is a recombinant human coagulation factor that is intended for promoting hemostasis through activation of the extrinsic pathway of the coagulation cascade. It does this by bypassing the coagulation cascade and creating a ―thrombin burst‖, thereby leading to a stable fibrin clot. There are numerous theories about the exact mechanism of rFVIIa in vivo. In hemophilia A and B (factor VIII and IX deficiencies), it has been shown that factor VIIa will bind to platelets and activate factor X to factor Xa, resulting in thrombin generation, despite deficiencies in the intrinsic pathway. There has also been shown to be a doseresponse relationship between the amount of rFVIIa and thrombin formation, so increasing doses of rFVIIa can increase thrombin generation even in the absence of factor VIII and IX. In addition to upregulation of thrombin formation, it has also been shown that rFVIIa inhibits fibrinolysis by activation of thrombin activatable fibrinolytic inhibitor in factor VIII-deficient plasma.