Intracranial hemorrhage before start of prophylaxis in children with hemophilia: incidence, timing, and potential for prevention
Nadine G. Andersson,
Marloes de Kovel,
Giancarlo Castaman,
Roseline d’Oiron,
Gili Kenet,
Christoph Konigs,
Christoph Male,
Beatrice Nolan,
Martin Olivieri,
Fernando Pinto,
Sigridur Sigurgisladottir,
Ester Zapotocka,
Kathelijn Fischer
Affiliations
Nadine G. Andersson
Center for Thrombosis and Haemostasis, Skåne University Hospital, Malmö, Sweden; Department of Paediatric Haematologu and Oncology, Skåne University Hospital, Lund, Sweden; Department of Clinical Sciences and Paediatrics, Lund University, Lund
Marloes de Kovel
PedNet Haemophilia Research Foundation, Baarn
Giancarlo Castaman
Department of Oncology Careggi University Hospital, Florence
Roseline d’Oiron
Centre de Référence de l'Hémophilie et des Maladies Hémorragiques Constitutionnelles, et HITh UMR_S1176 INSERM, Hopital Bicêtre, APHP Université Paris Saclay, Le Kremlin Bicêtre
Gili Kenet
National Hemophilia Center Sheba Medical center, Hashomer and Amalia Biron Research Institute of Thrombosis and Hemostasis, Aviv University
Christoph Konigs
Goethe University Frankfurt, University Hospital, Department of Paediatrics and Adolescent Medicine, Clinical and Molecular Haemostasis, Frankfurt
Christoph Male
Department of Paediatrics, Medical University Hospital of Vienna, Vienna
Beatrice Nolan
Department of Paediatric Haematology, Our Lady’s Children’s Hospital for Sick Children, Crumlin, Dublin
Martin Olivieri
Paediatric Thrombosis and Haemostasis Unit, Paediatric Haemophilia Center, Dr. von Hauner Children's Hospital, LMU Munich, Munich
Fernando Pinto
Paediatric Haematology, Royal Hospital for Children, Glasgow
Sigridur Sigurgisladottir
Department of Paediatric Haematologu and Oncology, Skåne University Hospital, Lund
Ester Zapotocka
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveld Kliniek, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University/University Hospital Motol, Prague, Czech Republic
Kathelijn Fischer
Medical Faculty, Masaryk University, Brno, Czech Republic
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. In total, 2727 children (2275 with HA; 452 with 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 1000 patient years), with 75% of cases occurring before one 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.
