Inhibitor epidemiology and genetic-related risk factors in people with haemophilia from Côte d'Ivoire

Introduction: In Sub-Saharan Africa, inhibitor prevalence data in people with haemophilia (PWH) are scarce, as are data on genetic or treatment-related risk factors.

Aims and methods: We performed a prospective study on PWH from Côte d'Ivoire to collect data into inhibitor prevalence, create a database of haemophilia genotypes, establish correlations between inhibitor presence and genetic variants identified amongst Ivoirian PWHs and evaluate exposure to CFCs.

Results: The study included 54 unrelated participants (43 severe, four moderate, two mild haemophilia A and five severe haemophilia B). PWH were treated on-demand with various product types for short periods, non-intensively, and using low-dose regimens. We reported similar distributions of intron 22 inversions (39.5%), point pathogenic variants (32.6%) and rearrangements in Ivoirian severe haemophilia A patients versus non-African ethnic groups. The haplotypes H1 (29.6%), H2 (36.3%) and H3 (34.1%) frequencies in haemophilia A were consistent with results published on African populations. We identified eight new causal variants. An inhibitor was found in 12% of haemophilia A patients previously exposed to replacement therapies. Among PWH with inhibitors, 66.7% had a positive intron 22 inversion and 50% the H1 haplotype.

Conclusion: This study provides original data on molecular diagnosis of haemophilia, inhibitor prevalence and risk factors for inhibitor development previously associated with inhibitors in Côte d'Ivoire. The low inhibitor prevalence likely reflects the limited exposure to replacement therapy in Côte d'Ivoire. Further larger, multicentric and international studies are needed to gain more insight on inhibitor incidence and risk factors in African PWH.