The bleeding phenotype in people with non-severe hemophilia.

Detailed information on the onset, frequency and severity of bleeding in non-severe hemophilia is limited. We aimed to assess the bleeding phenotype of people with non-severe hemophilia, and to analyse the association between baseline factor VIII/IX levels and the joint bleeding rate. In the DYNAMO study, an international multicenter cohort, we included males with non-severe hemophilia (factor VIII/IX (FVIII/IX) 0.02-0.35 IU/mL) aged 12-55 years. Information on age at first treated (joint) bleed and the annual (joint) bleeding rates (A(J)BR) were collected from the medical files. The association between baseline FVIII/IX levels and the joint bleeding rate was assessed using a frailty model for recurrent events. In total, 304 people (70 moderate and 234 mild hemophilia) were included. The median age was 38 years (IQR 25-49) and the median baseline FVIII/IX level was 0.12 IU/mL (IQR 0.05-0.21). In total, 245 (81%) people had experienced at least one bleed and 156 (51%) had experienced at least one joint bleed. The median age at first bleed and first joint bleed was 8 and 10 years, respectively. The median ABR and AJBR was 0.2 (IQR 0.1-0.5) and 0.0 (IQR 0.0-0.2), respectively. From baseline FVIII/IX levels 0.02-0.05 IU/mL to >0.25 IU/mL, the median ABR decreased from 0.6 (IQR 0.2-1.4) to 0.1 (0.0-0.2) and the AJBR from 0.2 (0.0-0.4) to 0.0 (0.0-0.0). Baseline FVIII/IX was inversely associated with the joint bleeding rate (p <0.001). Low bleeding rates were observed in people with non-severe hemophilia. However, half of all adolescents and adults had experienced a joint bleed.