This has not been tested in a controlled trial but has been reported to be successful in small series [9]. There has been little published on

the eradication of low titre inhibitors click here (peak titre <5 BU) but experience suggests that these are usually readily tolerized using a low-dose regimen. Progress on ITI is usually monitored firstly by measuring the inhibitor titre monthly and then, when the Bethesda titre is consistently negative, measuring the FVIII recovery monthly, without a washout. Once this has normalized (>66%), the half-life is usually measured after a 3-day washout every 3 months until normal [8]. A truncated half-life is probably adequate for this purpose and the ITI data are being re-analysed to determine whether the approach of Bjorkman to half-life estimation [23], which minimizes sample requirement may be appropriate. When all three of these parameters are normal, the patient is considered tolerant [8]. Most patients achieve tolerance within 6–12 months but a minority may take 1–3 years or more. ITI can be abandoned in such patients after 6–9 months RO4929097 supplier and

rescue therapy introduced if there is no evidence of a significant decline in inhibitor titre. ITI is also often stopped for logistic reasons, because of failure of venous access and/or repeated CVAD infection. Long interruptions in ITI are to be avoided because they are significantly associated with a poor outcome [24]. Patients whose inhibitor titres rise >500 BU are unlikely to succeed. Similarly patients whose titres fail to decline or continue to rise over a 6 month period are unlikely to be successfully tolerized and consideration should be given to either changing the regimen or stopping ITI. It is a matter of individual judgement when to consider Amino acid that the patient has failed ITI or should be changed to a different regimen. Options for rescue therapy in unresponsive patients are limited and there is insufficient data to recommend any specific strategy. The

alternatives include the use of a higher dose regimen, changing to pdFVIII with a high VWF content, adding immunosuppression such as Rituximab or both. Patients with mild haemophilia A who develop an inhibitor respond less well to immune tolerance than those with severe haemophilia [25] though these patients had a median age of 32 and inhibitors presenting earlier in life may be more likely to respond. Immune tolerance induction, ITI for haemophilia B must be carefully considered because of the relatively poor overall success rate (25%) and the risk of anaphylaxis and potentially irreversible nephrotic syndrome [5,6]. Regimens analogous to haemophilia A have been used including low- and high-dose FIX and a modified Malmo regimen [26]. The NAITR reported 31% success with a median dose of 100 U−1 kg−1 day−1 and 6/7 patients were successfully tolerized using the Malmo regimen [26].