Some patients can be treated successfully with desmopressin, especially those patients whose basal factor VIII level did not significantly decrease and whose inhibitor does not seem to cross-react with their endogenous factor VIII [25,33,34] or once an adequate circulating factor VIII level has been restored. Desmopressin does not cause anamnesis in those patients

despite the presence of high-responding inhibitors [25]. Published data on immune tolerance induction in patients with mild haemophilia and inhibitors are very scarce. In the series reported by Hay et al. [25], immune tolerance induction was attempted in eight patients using different regimens. The Malmo regime (high dose factor VIII combined with cyclophosphamide and i.v. IgG) was used successfully in two patients and with a partial response in further two patients. The Van Creveld regime (low dose factor VIII every other day) was used selleck screening library Autophagy inhibitor in vivo unsuccessfully in one patient and with partial success in a further patient and the Bonn regime was used unsuccessfully in one patient and with partial success in another patient. The overall success rate of immune tolerance

of two of eight patients seems lower than the reported success rate in severe haemophilia. Other reported treatments have included immunomodulatory drugs such as corticosteroids, cyclophosphamide, anti-CD20 monoclonal antibody rituximab [32,46–48] and avoidance of re-exposure to factor VIII using desmopressin and bypassing agents to treat bleeding episodes [49]. Currently available data are not sufficient to offer evidence-based advice on the optimal treatment of inhibitors in patients with mild

haemophilia A and the management of these patients remains controversial at this point. Preliminary data from a retrospective and prospective data collection in France and Belgium [16,50] suggest that immune tolerance induction could be more effective than no specific treatment or immunomodulating drugs in preventing risk of anamnesis of the inhibitor after re-exposure to factor VIII. In a meta-analysis on the MCE effectiveness of rituximab in patients with congenital haemophilia and inhibitors, complete responses were unexpectedly high in patients with mild haemophilia (12/16 patients) as compared with severe haemophilia (12/28) [51]. Maximal use of desmopressin for the treatment of patients with mild haemophilia A is certainly useful to prevent the development of inhibitors in these patients. Avoidance of intensive courses of treatment with factor VIII concentrates has to be considered especially in those patients known to harbour one of the high risk mutations or having a relative who developed an inhibitor. Patients with mild haemophilia are facing a tricky itinerary full of unexpected pitfalls.