Effects of “Primary Prophylaxis” and “On-Demand” Therapy on the Clinical Expression of Severe Hemophilia A in Children - Results of a Multicenter Study.

Background: Patients with severe hemophilia A (HA) can either be treated by regular FVIII infusions twice or thrice per week (prophylaxis), or only in case of bleeding episodes (on-demand). Whereas prophylaxis reduces the number of bleeding episodes and may therefore prevent the development of hemophilic arthropathy, recommendations regarding age and dose at start of prophylactic regimens are still a matter of debate. The present cohort study was performed to investigate the role of “primary prophylaxis” versus “on-demand” therapy in HA children. The outcome variable was imaging-proven hemophilic joint damage.

Methods: 42 children were initially treated with primary prophylaxis following the first bleeding episode, and were frequency-matched (year of birth, catchment area) to 67 patients receiving “on-demand” therapy with an early switch to “secondary prophylaxis”.

Results: In multivariate analysis adjusted for the HA mutation type and the presence or absence of thrombophilia, the Pettersson score investigated at a median age of 12.5 years in joints with at least one documented bleeding episode was no significantly different between the two patient groups (p=0.944), and no statistically significant differences were found in patients with target joints (p=0.3), or in children in which synovitis had occurred (p=0.77). Imaging results obtained showed a substantial agreement (87.14%) beyond that expected by chance alone (42.4%) between local and central readers in the patients tested (kappa=0.77; Z= 17.27; p < 0.001).

Conclusion: In cases with severe HA where primary prophylaxis is impossible, the procedure to switch from “on-demand” to early secondary prophylaxis can be achieved in the majority of young children affected. In addition, the needs of parents around the time of diagnosis of severe HA could be better addressed.