At patient level, the data on joint outcome suggest that a proportion of patients are equally well-off with intermediate-dose
prophylaxis, while others need a high-dose regimen to control their bleeding. Pharmacokinetic information [26] in combination with bleeding frequency and individual circumstances, such as sports participation [27], can be used to assist decisions on prophylactic dosing. Continued follow-up of these cohorts will provide us with some of the answers needed. Until then, personalizing prophylactic treatment, including lower dosed regimens, appears the most cost-effective treatment strategy. Regular factor infusions to prevent bleeding have become the mainstay of treatment for many patients with haemophilia. Numerous Dabrafenib research buy observational studies and one randomized controlled trial have documented that the efficacy of
prophylaxis started early in life reduces bleeding and prevents joint damage [28, 29, 6, 30]. Even when instituted later in life, after joint damage has occurred, prophylactic RO4929097 factor therapy can significantly reduce the number of bleeds including into joints, although data on long-term joint outcomes are still limited [30, 8, 9]. These results have raised the question of whether prophylaxis could be effective in patients with haemophilia and inhibitors to FVIII or FIX. This question has been addressed in case reports, case series, and in randomized trials. Patients with haemophilia and persistent inhibitors are more likely to have disabling haemophilic arthropathy and other sequelae of bleeding [31]. While the use of bypassing agents [recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrates (aPCC)] has advanced care of patients with inhibitors, these products are not as effective overall as factor replacement therapy and bleeding results in persistent adverse effects. If
prophylactic therapy with bypassing agents could prevent bleeding, there is the potential for even more benefit in the inhibitor population from this approach. Multiple reports have relayed successful use of either medchemexpress rFVII or aPCC in a prophylactic regimen, although with varying dosing and treatment intervals [27, 32, 33]. In general, these reports document decreased bleeding, improved quality of life, and often the ability to support a rehabilitation regimen, albeit in small numbers of patients. Three randomized controlled trials which evaluated prophylaxis in inhibitor patients have now been reported, one with rFVIIa and two with aPCC [34-36]. In the study subjects, generally patients with a history of frequent bleeding episodes, there was a significant decrease in bleeding with prophylactic therapy. There were no thrombotic complications and two allergic reactions to the aPCC.