Blood Group O Does Not Increase the Risk of Inhibitors in Severe Haemophilia A: Data from the PedNet Study Group

Authors: Kovel, M de; van Haaster, A-C; Carcao, M; Ranta, S; Glosli, H; Rivard, GE; Kenet, G; Kurnik, K; van Geet, C; Carvalho, M; Andersson, NG; Kartal-Kaess, M; Ljung, R; van den Berg, H Marijke

Affiliations: PedNet Haemophilia Research Foundation, Baarn, the Netherlands. PedNet Haemophilia Research Foundation, Baarn, the Netherlands. Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Canada. Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden. Centre for Rare Disorders Oslo University Hospital, Oslo, Norway. Division of Hematology/Oncology, Hôpital St Justine, Montréal, Canada. National Hemophilia Center, Sheba Medical Center, Tel Hashomer and Amalia Biron Research Institute of Thrombosis and Hemostasis, Tel Aviv University, Tel Aviv, Israel. Paediatric Thrombosis and Haemostasis Unit, Paediatric Haemophilia Center, Dr. von Hauner Children’s Hospital, LMU Munich, Munich, Germany. Department of Pediatrics, Pediatric Hematology and Oncology, University Hospitals Leuven, Leuven, Belgium. Centro de Referência de Coagulopatias Congénitas do Centro Hospitalar Universitário S. João, EPE, Porto, Portugal. Center for Thrombosis and Haemostasis, Skåne University Hospital, Malmö, Sweden. Department of Paediatric Haematology and Oncology, Skåne University Hospital, Lund, Sweden. Department of Clinical Sciences and Paediatrics, Lund University, Lund, Sweden. Division of Pediatric Hematology and Oncology, Department of Pediatrics, Inselspital, University Hospital, University of Bern, Bern, Switzerland. Department of Paediatric Haematology and Oncology, Skåne University Hospital, Lund, Sweden. PedNet Haemophilia Research Foundation, Baarn, the Netherlands.

Publication: Haemophilia; 2025

ABSTRACT: INTRODUCTION: Inhibitor development against factor VIII (FVIII) is the most common complication of hemophilia A replacement therapy. One of the variables considered to influence inhibitor development is the ABO blood group. Patients with blood group O have on average, a 30%-40% lower endogenous von Willebrand factor (VWF) concentration. It has been postulated that VWF levels influence inhibitor development. The objective of this study was to investigate the inhibitor risk in patients with severe hemophilia A comparing those with blood group O with those with non-O blood groups. METHODS: The study population consisted of children with severe hemophilia A, born between 2000 and 2020, who reached 50 FVIII exposure days in the PedNet registry. Inhibitors were considered to be clinically relevant when at least two consecutive measurements were tested positive. RESULTS: Routine testing of blood groups varied between centres: Out of 1172 patients with severe hemophilia A, blood group status was known in 759 patients (65.8%). The relative risk of inhibitor development for blood group O in comparison to non-O was 1.04 (95% CI: 0.7-1.7). CONCLUSION: In the PedNet cohort, blood group O did not increase the risk of inhibitors in previously untreated children with severe hemophilia A. TRIAL REGISTRATION: PedNet Registry; clinicaltrials.gov identifier: NCT02979119.