Since inhibitors usually occur

Since inhibitors usually occur GSK126 in vitro within the first 50 EDs, many physicians prefer not to switch FVIII products during this time. On the other hand, it should be acknowledged that switching between different FVIII products was not associated with an enhanced risk of inhibitor development in the large cohorts of patients with <50 EDs evaluated in the CANAL and RODIN studies [13, 14]. Similarly, intensive treatment and/or surgery are well known determinants of inhibitor development [36, 37]. Therefore, it sounds reasonable to avoid switching FVIII product in the

peri-operative period, although, no robust evidence is available to support a specific role of product switch in the inhibitor formation after surgery and intensive treatment [36, 37]. Patients with a family history of inhibitors or a severe F8 gene

defect are also known to be at high inhibitor risk, however, no observation has been reported in the literature indicating an increased inhibitor risk when switching FVIII selleck products in these conditions. Patients with a previous history of inhibitors, including those who achieved success after immune tolerance induction (ITI), are usually considered at risk of inhibitor recurrence. It may be reasonable to surmise that, in this situation, the introduction of a new FVIII product could break the tolerance to FVIII. On the other hand, successful ITI outcome was reported with FVIII products different from that eliciting the inhibitor formation [57]. In patients with MHA inhibitor

prevalences between 3% and selleck kinase inhibitor 13% are reported, but these cross-sectional studies did not take exposure to FVIII concentrate into account [3-6]. As patients with MHA receive factor VIII replacement therapy infrequently for bleeds or surgery, it is especially important to express the inhibitor risk as a function of EDs. This was done in the INSIGHT study that included 2711 persons with MHA (FVIII 0.02–0.40 IU mL−1) from Europe and Australia [7]. The inhibitor risk at 50 EDs was 6.7% (95% CI, 4.5–8.9) and at 100 EDs the risk further increased to 13.3% (95% CI, 9.6–17.0). Furthermore, this study demonstrated that the risk of inhibitor development in patients with MHA remains present after 50 EDs and even after 100 EDs. Thus, in contrast to severe haemophilia A the risk of inhibitor development does not level off after 50EDs and patients with MHA are at lifelong risk of inhibitors, requiring continuous vigilance. This necessitates frequent testing for inhibitors, especially after intensive FVIII replacement for major bleedings or surgery. Inhibitors in patients with MHA develop at a median age of 37 years after a median of 29 EDs [7, 8] In about half the patients (57%), the baseline FVIII drops below 0.01 IU mL−1 as the inhibitor cross-reacts with the endogenous FVIII, changing the phenotype into severe haemophilia A [7].

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