Combination of hemostatic therapies for treatment of patients with hemophilia A and inhibitors

Background: Therapy application and monitoring of patients with hemophilia A (HA) and inhibitors are challenging. In the current study, combined FVIII -bypass therapy was implemented for a cohort of severe HA patients with inhibitors. Methods: Plasma of 15 HA patients with inhibitors was spiked ex vivo with FVIII, rFVIIa, FEIBA and their combinations and thrombin generation (TG) was studied. Some patients who experienced hemarthroses or required minor surgeries were treated by a combined concomitant administration of FVIII + FEIBA as IV bolus doses. Results: TG spiking studies showed individual responses not correlated to inhibitor titer. Combinations of agents augmented TG as compared to any single agent, while combined FVIII + FEIBA yielded the highest TG, supporting it as a potential treatment. Following emergent successful surgery of child treated by concomitant FVIII + FEIBA, a total of 396 episodes in 7/15 patients were treated with concomitant FVIII + FEIBA. Five patients were treated for bleeding episodes only, whereas 2 were children undergoing immune tolerance induction (ITI) with FEIBA prophylaxis. Four minor surgeries were performed on FVIII + FEIBA repeated infusions. Neither thrombosis nor any other adverse events were documented. Conclusion: A combination of FVIII + FEIBA may be effective and safe as an alternative treatment option for some high-responding inhibitor patients.