According to Deana Gordon and colleagues at the University of Colorado at Aurora, CO, children with hemophilia A and high-titer inhibitors suffer frequent severe bleeding events and often respond to bypassing agents more poorly than adults, resulting in increased dosing and cost.
The investigators designed a prospective inceptional cohort study of bleeding disorders. Those pediatric subjects with hemophilia A who developed high-titer inhibitors were treated with immune tolerance induction. Children treated with bypassing agents primarily represent difficult inhibitors. Treatment was given as VIIa (n=28), prothrombin complex concentrates (n=10), or alternating doses of both (n=12).
Following data analysis, children were found to receive seven times the treatment doses and duration as adults. In addition, children received both recombinant factor VIIa and prothrombin complex concentrates for half of the bleeding events, while this regimen was used for only one adult event. Treatment duration in children was not affected by initial dose or dose frequency of VIIa (P >0.05 for both). Bleeding events were severe and difficult to manage; significant long-term morbidity in these six children include ankle arthropathy in three, elbow contracture following compartment syndrome in two, and quadrucep pseudotumor in two.
The investigators concluded that children with hemophilia A and inhibitors experience bleeding episodes that are poorly responsive to both VIIa and prothrombin complex concentrates, resulting in higher dosing, longer duration, and enormous costs.