7. Of interest, the patients who were able to permanently discontinue prophylaxis appeared to have a milder bleeding phenotype as evidenced by having a later start

of prophylaxis, requiring a lower weekly dose of factor replacement and experiencing a lower joint bleed frequency on prophylaxis [38]. In Denmark, 10 of 22 cases (45%) studied at a median age of 26.2 years were able to permanently discontinue prophylaxis [39]. Long-term studies are now required to determine the musculoskeletal consequences of discontinuing long-term factor prophylaxis in early adulthood. Use of secondary prophylaxis in adults with severe haemophilia is increasing in countries with access to safe FVIII and FIX concentrates. This practice is supported by results from prospective studies. In a longitudinal Selleckchem 3-deazaneplanocin A study of buy Daporinad 477 patients under 25 years of age with severe haemophilia A, prophylaxis for >45 weeks year−1 significantly reduced the rate at which joints deteriorated both on physical and X-ray examinations [8]. Patients on long-term prophylaxis had significantly fewer days lost from work or school as well as fewer days spent in hospital. The investigators concluded that ‘a haemophiliac may well be better served with prophylaxis as the treatment regimen’ [8]. Recently, Collins and colleagues have reported

the results of a cross-over study comparing on-demand treatment with full-dose prophylaxis in 20 adults ages 30–45 years of age with severe haemophilia A

and selleck compound an average of two bleeds per month [40]. Subjects received on-demand treatment for 6 months and were then switched to a high-dose prophylaxis regimen for 7 months. The first month of prophylaxis was considered a run-in period to allow stabilization on the prophylaxis regimen. Compared to on-demand treatment, prophylaxis was associated with a significant reduction in the frequency of joint bleeds (median 0 vs. a median of 15 for on-demand treatment). Of note, postinfusion FVIII trough levels were >5% at 48 h in 75% of cases and ≥2% at 72 h for 57% of patients. These studies provide a foundation in support of secondary prophylaxis in adults, and suggest that, in general, adults will require lower total doses of FVIII or FIX compared with children to maintain equivalent trough FVIII/FIX levels. The lower dose requirement in adults is predictable from the fact that FVIII half-life tends to be longer in adults than in small children 41, 42). Stabilization of clotting factor consumption in adulthood for subjects who receive early intensive prophylaxis has been reported by Dutch investigators [43]. The beneficial role of primary prophylaxis in young boys with severe haemophilia can no longer be questioned.