Recombinant activated factor VII: its mechanism of action and role in the control of hemorrhage.
OBJECTIVE
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.


METHODS
A review of the literature was performed to determine those clinical scenarios in which rFVIIa appears to have been effective in controlling associated hemorrhage.


RESULTS
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.
Allen
Geoffrey A
GA
Center for Thrombosis and Hemostasis and Pediatric Hematology/Oncology, University of North Carolina School of Medicine, Chapel Hill 27599-7220, USA. allen@med.unc.edu
Hoffman
Maureane
M
Roberts
Harold R
HR
Monroe
Dougald M
DM
D001777:Blood Coagulation; D005167:Factor VII / Q000494:pharmacology* / Q000627:therapeutic use; D005168:Factor VII Deficiency / Q000188:drug therapy; D015942:Factor VIIa; D005173:Factor XI Deficiency / Q000188:drug therapy; D006467:Hemophilia A / Q000188:drug therapy; D006470:Hemorrhage / Q000188:drug therapy*; D006490:Hemostatics / Q000494:pharmacology*; D006801:Humans; D011994:Recombinant Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000188:drug therapy
D006490:Hemostatics; D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa