Intracranial hemorrhage before start of prophylaxis in children with hemophilia: incidence, timing, and potential for prevention

Abstract

Children with hemophilia have a significantly higher risk of intracranial hemorrhage (ICH) compared to the normal population. Prophylaxis reduces the risk of ICH and earlier initiation of prophylaxis may now be feasible, especially in hemophilia A (HA). The aim of the study is to explore the potential for preventing ICH by earlier start of prophylaxis by assessing the natural course of ICH before the initiation of prophylaxis and describe timing and incidence (clinicaltrials gov. Identifier: NCT02979119). In total, 2,727 children (2,275 with HA; 452 with hemophilia B [HB]) were included from the PedNet Registry, followed from 28 days until 36 months of life. ICH was observed in 61 children (incidence 2.2%; 10 per 1,000 patient years), with 75% of cases occurring before 1 year of age. Cumulative incidence was significantly lower in HB (0.9%) compared to HA (2.5%) and in non-severe HA (0.7%) compared to severe HA (3.5%). ICH occurred early, with a rise at 3 months, and a median age of 7.0 months in severe HA and 5.4 months in severe HB. In 40% of children, ICH occurred before the diagnosis of hemophilia was established, underscoring the importance of early diagnosis. Assuming that prophylaxis would have been started at the time of diagnosis and preventing all ICH in children with severe HA, the number needed to treat with prophylaxis would be 44 patients to prevent one ICH. Hopefully, prophylaxis options allowing initiation early in life, ideally before 3 months of age for children with severe HA, will reduce the incidence of ICH in the future.