In addition, prophylaxis might exert a favourable immunological effect to

promote tolerance. However, to better appreciate the immunological effect well-designed prospective studies are needed. This is also the case for evaluating the optimal dosing and when to start treatment. Haemophilia registries and large cohort studies can provide considerable insight. In all cases, however, the genetic aspects must be taken into account. It has been postulated that challenges to the immune system (such as infections or vaccinations) or genetic factors involving immune response genes and cytokine production might influence inhibitor formation in patients with haemophilia [13, 22]. It has also been suggested that extensive learn more tissue damage and inflammation may trigger an antibody response against extra-vascular FVIII [22]. Our search showed that there is find more a paucity of studies investigating these risk factors (Table 3) [13,16,23]. One case–control study [13] has investigated vaccination or infection in 60 patients and 48

control subjects. Infections were present, or vaccinations performed, during active FVIII treatment in 12 patients and 11 controls. Although no apparent association was found between vaccination or infection and the development of inhibitors, no conclusions could be drawn as this was a single study in which selection bias could not be ruled out. Similarly, only one study that considered blood components could be identified. This study [23] was difficult to evaluate, as the patient group was heterogeneous with respect to the type of blood products received. In a recent case–control study, acute hepatitis was frequently reported within 4 months of inhibitor detection and did not occur at all in matched controls [16]. HBsAg positivity was associated with inhibitor development, suggesting a higher risk of inhibitors in association with infection. No association with vaccination was described. Two studies addressed the initial exposure to blood components and inhibitor formation selleckchem [16,23]. In the case–control study, inhibitor patients had received significantly more FVIII concentrates and

less non-concentrate products than controls. No conclusions can, however, be drawn from these two studies, as the study groups were small, not well-defined and heterogenous with respect to the timing and type of blood products received. Survey.  With the exception of infections, clinical experience within the group would suggest that the majority rated these factors as of moderate to low importance (3–1) in inhibitor development (Fig. 1), and their influence on clinical practice was also moderate to low (Fig. 2). When rated on a scale of 0–100 there was a wide variation of opinion. Infection was the only parameter consistently reported to be of moderately high importance and impact clinical practice (Fig. 1). Recommendation.