Dose or Timing? The Role of Prophylaxis in Preventing Joint Bleeds in Hemophilia: A Cross-Generational Comparative Analysis

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BACKGROUND: This study aimed to assess intergenerational differences in joint health and functional independence among adults with hemophilia and to examine the relationship between prophylaxis timing, dose intensity, and treatment adherence and long-term joint outcomes. METHODS: A retrospective study was conducted including 91 adult patients with hemophilia A or B. Participants were classified into generational cohorts within different treatment eras. Joint health and functional status were assessed using the Hemophilia Joint Health Score (HJHS) and the Functional Independence Score in Hemophilia (FISH). Statistical analyses included correlation analyses, subgroup comparisons, and general linear models; subgroup analyses were considered exploratory. RESULTS: The median age was 38 years, and prophylaxis was initiated at a median age of 27 years. Patients had a mean annual bleeding rate of 11.1, with a median of 2 joints affected per year, most commonly the ankles, knees, and elbows. The median prophylaxis dose was 20.8 IU/kg, and bleeding episodes significantly decreased in patients requiring dose escalation (P = .007). Higher joint scores were associated with poorer functional outcomes and a greater number of bleeding joints. Joint health and functional outcomes differed significantly across generations (P < .001), with worse outcomes in older cohorts. Follow-up showed no significant improvement over 1 year, although baseline and follow-up joint scores were strongly correlated (P < .001). CONCLUSION: In adults with hemophilia, delayed prophylaxis initiation was associated with poorer joint and functional outcomes. The observed intergenerational differences likely reflect historical variations in access to prophylaxis and treatment practices. Although individualized dose escalation improved bleeding control, established joint damage showed limited short-term reversibility. Cite this article as: Demirci Z, Soyer N, Keklik Karadağ F, Arslan A, Saydam G, Şahin F. Dose or timing? The role of prophylaxis in preventing joint bleeds in hemophilia: a cross-generational comparative analysis. Eurasian J Med. 2026, 58(4), 1208, doi: 10.5152/eurasianjmed.2026.251208.

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