Critical appraisal of the role of recombinant activated factor VII in the treatment of hemophilia patients with inhibitors

Abstract

Hemophilia patients with inhibitors faced the constraint of inadequate treatment for several years before the era of recombinant factor VIIa (rFVII). Initially, rFVIIa was used in the compassionate-use programs. After a worldwide license was issued, more than 1.5 million doses were administered. Bleeding of joints and muscles was controlled effectively by means of an early home treatment program, with either a standard dose of 90 μg/kg every 2 to 3 hours for a few doses or a single dose of 270 μg/kg. For more serious bleeding episodes or minor surgery, an initial dose of 90 μg/kg was given every 2 hours for 24 to 48 hours followed by increased intervals of 3 to 6 hours according to the severity of bleeding and efficacy of bleeding control. In cases of major surgery such as orthopedic procedures, the same regimen can be applied except for a higher initial dose of 120 to 180 μg/kg. However, increasing the dose should be considered if there are unexpected bleeding complications since the half-life and clearance of rFVIIa differ between individuals. In addition, prophylaxis is administered to a small number of patients. Finally, the reported thromboembolic events found in hemophilia patients with inhibitors receiving rFVIIa are extremely low, much less than 1%.

Renal thromboembolism during treatment with recombinant activated factor VII (rFVIIa) in a child with hemophilia B with factor IX inhibitors

“…However, when rFVIIa is used in labeled indications such adverse event is rare and did not appear to be dose-related. The incidence of serious thromboembolic events after treatment with rFVIIa in hemophilia patients with inhibitors appears to be much less than 1%, with only three cases reported in children, all of them with hemophilia A and predisposing factors [ 2 - 4 ].…”