Dose optimization of recombinant factor VIIa for control of mild to moderate bleeds in inhibitor patients: improved efficacy with higher dosing

Abstract

Optimal dosing schedules of recombinant factor VIIa (rFVIIa) for the treatment of mild to moderate bleeding episodes in hemophilia patients with inhibitors are currently the subject of much debate. Standard doses of 90 to 110 μg/kg have provided hemostatic efficacy in many cases in the current literature. However, recent studies using doses greater than 200 μg/kg suggest that high-dose regimens may not only be more effective, but may also reduce the number of doses required. Work using in vitro models has indicated that the increased efficacy of high-dose rFVIIa may be attributed to accelerated clot formation and a stronger, more rapid thrombin burst on the surface of activated platelets. Before higher dosing schedules become more widely used, however, a number of unanswered questions remain to be resolved. It is expected that ongoing and future trials will help to clarify some of these issues. Until such information is available, it is recommended that children and adolescents may be treated with a single bolus dose of 300 μg/kg rFVIIa within 1 to 2 hours of bleed onset. Due to a current lack of information regarding high-dose rFVIIa therapy in adults, however, it would be prudent to use standard doses (90 μg/kg every 2 to 3 hours for two or three doses) in this patient population.