Genotyping can identify which patients with MHA are at increased risk of inhibitor development due to a high risk missense mutation. In these high-risk patients, alternative treatment options such as desmopressin (DDAVP) or bypassing agents should be considered whenever they need surgery or intensive treatment for a large bleed. Once an inhibitor has emerged, bleeds may be treated by DDAVP when measurable

FVIII levels are present. If the response to DDAVP is not X-396 cost adequate or when prolonged hemostatic activity is necessary, FVIII bypassing agents are required, such as recombinant FVIIa (Novoseven®) or activated prothrombin complex (FEIBA®) [62]. In patients with MHA and inhibitors, avoidance of FVIII concentrate is usually associated with a decline in inhibitor titer. However, re-exposure to FVIII concentrates will often elicit an anamnestic response [8, 9]. Therefore, unless uneventful rechallenge with therapeutic FVIII concentrates has been documented, these patients should not be regarded as “complete remissions” or “successful tolerization”. In patients with reduced endogenous FVIII levels and a severe bleeding phenotype, it is important to achieve

baseline FVIII levels again to mitigate the bleeding phenotype. ITI or immune modulation may be initiated to eradicate the antibodies [62]. The effect of these therapeutic approaches in patients with MHA has not Syk inhibitor been studied formally. Small ITI case series suggest that traditional ITI regimens used in severe haemophilia A are less efficacious in MHA, with a <30% ‘success’ rate [8, 9, 63]. Case series of Rituximab use have been reported [64-66] and

a literature review [67] suggests a higher than expected success rates (12/16, 75%). This figure should be treated with caution as there may be reporting bias of successful cases and it remains unclear whether cases were re-challenged with FVIII to establish true tolerance, however, it does illustrate an important difference between the eradication of inhibitors in MHA and severe haemophilia A. ES received speaker fees by Baxter, Biotest, selleck inhibitor Kedrion and Octapharma, acted as a payed consultant for Bayer, CSL Behring and Grifols and received unrestricted research grants from Novo Nordisk and Pfizer. KF has received unrestricted research funds from CSL Behring, Pfizer, Novo Nordisk and Bayer, and has given lectures at educational symposiums organised by Pfizer, Baxter and Bayer. DL has received research funds from Bayer, Baxter, Biogen-Idec and CSL Behring. “
“Summary.  Recombinant coagulation factor VIII (rFVIII) concentrates provide a safe and efficacious replacement therapy for treatment and prevention of bleeding in patients with severe haemophilia A. The aim of this study was to compare the pharmacokinetic (PK) and safety profiles of two serum-free rFVIII products: N8, a new rFVIII manufactured by Novo Nordisk and Advate®, a marketed product.