The emerging role of recombinant-activated factor VII in neurocritical care.

Recombinant-activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Denmark) was developed specifically for the management of bleeding in hemophiliacs with inhibitors to factors VIII or IX. Several recent case reports and small clinical studies also suggest that rFVIIa may be useful as a general hemostatic agent in nonhemophilic patients. The mechanism by which rFVIIa acts is controversial with both tissue factor-dependent and -independent mechanisms proposed. Regardless of the specific mechanism, rFVIIa enhances hemostasis at the site of injury without systemic activation of the coagulation cascade. Several features make rFVIIa an ideal candidate for reversal of coagulopathy in central nervous system (CNS) hemorrhage. It acts almost immediately, requires negligible volume for infusion, poses no risk of transfer of blood-borne pathogens, and has few apparent complications. To date, clinically proven efficacy for rFVIIa by randomized controlled trials has been accomplished mainly for hemophilic patients. However, there are ongoing or planned clinical trials for rapid reversal of coagulopathy in trauma and liver disease, as well as CNS hemorrhage associated with oral anticoagulation and minimization of hematoma expansion after intracerebral hemorrhage. These trials will hopefully answer unresolved questions regarding risk-benefit ratio, therapeutic index, efficacy, safety, indications, optimal dosing, monitoring, and cost-effectiveness of rFVIIa in nonhemophilic patients.