Effect of FVIII doses on joint structure and function in adolescents with severe hemophilia A: mid-term results of a prospective cohort study

Abstract

To explore the clinical phenotype and changes in joint structure and function in adolescent patients with severe hemophilia A under different doses of FVIII. Forty- three adolescents with severe hemophilia A aged 4-18 years were divided into on-demand group (n=7), low-dose group (FVIII dose of 10-15 U/kg, 2-3 times a week, and ≤30 U/kg a week; n=17), and intermediate-dose group (FVIII dose of 15-20 U/kg, 2-3 times a week, and 45-60 U/kg a week (n=19). The 3 groups were compared for their clinical bleeding phenotype, annual bleeding rate (ABR), annual joint bleeding rate (AJBR), annual the most severe joint bleeding rate, joint imaging scores (ultrasound HEAD-US score and IPSG MRI score), Hemophilia Joint Health Score (HJHS) and Functional Independence Score in Hemophilia (FISH) within 24 months. Compared with that in on-demand group, the ABR was significantly reduced in the low- and intermediate-dose groups (P=0.004 and 0.000, respectively), and was reduced by 32.87% in the intermediate-dose group as compared with the low-dose group. The AJBR (P < 0.01) and annual the most severe joint bleeding rate (P < 0.05) also differed significantly among the 3 groups. The number of bleeding episodes increased progressively with time in the on-demand group, remained stable in the low- dose group, and tended to decrease in the intermediate-dose group. The imaging scores of the most severe joints showed lesion progression in all the 3 groups. The ultrasound scores, which increased steadily in the on-demand group, showed significantly lowered increment rates in the low- and intermediate-dose groups (P=0.002 and 0.000, respectively). The MRI scores showed also delayed increment in the low- and intermediate-dose groups as compared with the on-demand group (P=0.041 and 0.000, respectively), and the increment was accelerated in the on-demand and low-dose group but remained stable in the intermediate-dose group. The increment of the HJHS scores was significantly higher in the on-demand group than in the lowand intermediate-dose groups (P=0.003 and 0.000, respectively), and the scores increased at a steady rate in the on-demand group but tended to decrease in the latter two groups. The FISH score was decreased by 0.29±3.09 in the on-demand group but was increased significantly in the low- and intermediate-dose groups compared with the on-demand group (P=0.000). In Chinese adolescents with severe hemophilia A, low- and intermediate-dose FVIII prophylaxis, especially at the intermediate dose, is better than on- demand treatment for protecting joint structure and function.