The ‘high-dose’ Malmö prophylaxis protocol

was aimed to maintain trough FVIII and FIX levels above 1%. Breakthrough joint bleeds were treated with one or more infusions of FVIII or FIX (25–40 IU kg−1) according to severity and until bleeding had stopped. It was recommended that prophylaxis continue life-long. In the Netherlands, prophylaxis was started at an early age according to the individual’s bleeding pattern, generally after the occurrence of at least one or two joint bleeds. The Midostaurin concentration Dutch regimen involved the administration of 15–25 IU kg−1 of FVIII two or three times a week for haemophilia A cases, and 30–50 IU kg−1 of FIX once or twice a week for haemophilia B cases. The intensity of prophylaxis was adjusted based on spontaneous breakthrough bleeding into joints and not increased according to the subject’s body weight alone. Trough levels of FVIII or FIX were not taken into consideration when adjusting prophylactic treatment. MS 275 It was recommended that prophylaxis continue throughout adulthood. The Canadian dose-escalation primary prophylaxis study was started in 1997. In this single arm, prospective study, boys’ ages 1 year to 30 months with severe haemophilia A, no evidence of a circulating inhibitor to FVIII and absence of any overt joint disease were

started on once weekly infusions of FVIII (50 IU kg−1). If clinically significant bleeding into muscles and/or joints occurred, the frequency of FVIII infusions was increased to twice weekly (dose 30 IU kg−1); continuation of bleeding resulted in escalation of the prophylaxis regimen medchemexpress to 25 IU kg−1 on alternate days. Criteria for escalation included: ≥ 3 clinically determined bleeds into any one joint over a consecutive 3-month period; ≥ 4 significant soft tissue/joint bleeds over a consecutive 3-month period and ≥ 5 bleeds into any one joint while on the same dosage (step) of factor therapy over any period of time. The interim results of this study have been reported [16], and 10-year follow-up results were presented at the 2009 International

Society on Thrombosis and Hemostasis Congress [22]. The Canadian primary prophylaxis study is now closed to patient accrual, but follow-up of enrolled cases is ongoing. Key results from these three long-term prophylaxis studies are as follows: 1 Compared to on-demand therapy, intermediate-dose prophylaxis (the Dutch protocol) started at an early age in boys with severe haemophilia results in significantly fewer joint bleeds, a better joint status and a more favourable health-related quality of life [20]. The results of the retrospective Swedish and Dutch cohort studies continue to be debated. At the centre of this debate is the issue of when should primary prophylaxis be started in boys with haemophilia A? Data from the Swedish and Dutch studies suggest that primary prophylaxis should be started at an early age but can be individualized based on the bleeding pattern in the individual child [23,24].