PURPOSE: Recombinant activated factor VII (rFVIIa) has proven both safe and efficacious in the treatment of bleeding episodes in patients with hemophilia A or B who have developed inhibitors. More recently, a growing number of reports suggests that rFVIIa may also have indications for the treatment of bleeding in patients with other hemostatic disorders, including qualitative and quantitative platelet defects, factor deficiencies other than hemophilia, and in otherwise healthy patients with uncontrollable hemorrhage following surgery or trauma. We have attempted to reconcile the various proposed mechanisms of action of rFVIIa with its apparent efficacy in such diverse clinical settings. SOURCE: A review of the literature was performed to determine those clinical scenarios in which rFVIIa appears to have been effective in controlling associated hemorrhage. PRINCIPAL FINDINGS: Findings from our group and others have demonstrated that rFVIIa is able to directly activate factor X and increase thrombin production on the surface of activated platelets in the absence of factor VIII or IX, as well as to improve thrombin generation in thrombocytopenia, and to yield a fibrin dot more resistant to fibrinolysis in vitro. CONCLUSIONS: Through these primary mechanisms, we believe that rFVIIa may be able to compensate for a variety of defects in hemostasis and merits further investigation as a general therapeutic for uncontrollable hemorrhage.
PURPOSE: Recombinant activated factor VII (rFVIIa) has proven both safe and efficacious in the treatment of bleeding episodes in patients with hemophilia A or B who have developed inhibitors. More recently, a growing number of reports suggests that rFVIIa may also have indications for the treatment of bleeding in patients with other hemostatic disorders, including qualitative and quantitative platelet defects, factor deficiencies other than hemophilia, and in otherwise healthy patients with uncontrollable hemorrhage following surgery or trauma. We have attempted to reconcile the various proposed mechanisms of action of rFVIIa with its apparent efficacy in such diverse clinical settings. SOURCE: A review of the literature was performed to determine those clinical scenarios in which rFVIIa appears to have been effective in controlling associated hemorrhage. PRINCIPAL FINDINGS: Findings from our group and others have demonstrated that rFVIIa is able to directly activate factor X and increase thrombin production on the surface of activated platelets in the absence of factor VIII or IX, as well as to improve thrombin generation in thrombocytopenia, and to yield a fibrin dot more resistant to fibrinolysis in vitro. CONCLUSIONS: Through these primary mechanisms, we believe that rFVIIa may be able to compensate for a variety of defects in hemostasis and merits further investigation as a general therapeutic for uncontrollable hemorrhage.
Authors: Daniel N Darlington; Igor Kremenevskiy; Anthony E Pusateri; Michael R Scherer; Chriselda G Fedyk; Bijan S Kheirabaldi; Angel V Delgado; Michael A Dubick Journal: Int J Burns Trauma Date: 2012-03-15