The bleeding phenotype in people with non-severe hemophilia.
Kloosterman FR., Zwagemaker A-F., Bagot C., Beckers EA., Castaman G., Cnossen MH., Collins PW., Hay CR., Hof MH., Laros-van Gorkom B., Leebeek FWG., Male C., Meijer K., Pabinger I., Shapiro S., Coppens M., Fijnvandraat K., Gouw SC.
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.