Acquired hemophilia A: a narrative review and management approach in the emicizumab era

Abstract

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by inhibitory autoantibodies to factor (F)VIII. The goals of treatment are 2-fold, namely immunosuppressive therapy to eradicate the inhibitor and hemostatic management to control bleeding. Emicizumab, a bispecific antibody that acts as a FVIIIa-mimetic, has seen growing use in AHA following its approval for congenital hemophilia A. This review provides an overview of the epidemiology, pathophysiology, diagnosis, and treatment of AHA. Registry, trial, and case series data are assimilated and summarized with an emphasis on a standardized approach that integrates the use of emicizumab. With recent registry data suggesting the need to focus on immunosuppression-related mortality in AHA, we provide treatment recommendations in an algorithmic format that have become the standard of care at our institution. These recommendations are intended to minimize hemostatic product usage and potential toxicity related to immunosuppressive therapy while reducing morbidity and rehospitalization rates for bleeding. The proposed treatment algorithm, which includes key interventions by phase of therapy, can be readily implemented at centers that have rapid access to plasma FVIII activity using a one-stage assay. A case is presented to illustrate the proposed diagnostic and management considerations.

Keywords: acquired bleeding disorders; acquired hemophilia; emicizumab; immunosuppression; porcine factor VIII.