Inhibitors

This study longitudinally observes the intergenerational (mother-child) continuum in hemophilia A from pregnancy through early childhood. Because the study follows mother-child pairs, the study includes both a maternal cohort and a pediatric cohort. Each cohort has a primary goal: for the mother with a severe hemophilia genotype, the overarching primary goal is to understand the risks for pregnancy-associated bleeding and postpartum hemorrhage (PPH); for the child, the overarching primary goal is to understand the risks, timing, and circumstances of development of anti-FVIII antibodies. From a longitudinal perspective, risks for both bleeding in the mother and anti-FVIII antibody development in the child are expected to be influenced over time by genetic and environmental factors that begin early in (or before) pregnancy. Enrollment of blood relatives is offered to improve power to better understand inherited contributions to bleeding and inhibitor development in the mother-baby pairs.

This study is a multicenter, prospective, single-arm exploratory clinical trial designed to evaluate the efficacy and safety of prothrombin complex concentrate (PCC) in the treatment of bleeding episodes in patients with hemophilia A with inhibitors. All participants received on-demand PCC therapy during bleeding episodes, with dosing adjusted by investigators according to the type of bleeding. The recommended dose was 50 IU/kg per infusion, administered every 8-12 hours, with a maximum total daily dose not exceeding 150 IU/kg. If no effective hemostasis was achieved within 24 hours, investigators could decide to add other hemostatic agents or switch to alternative treatments.