The development of inhibitors to factor replacement therapy, currently the most serious iatrogenic complication that affects patients with haemophilia [8–10], has profound effects on strategies

for continuing therapy. A better understanding of the causes and circumstances of inhibitor development might be useful to prevent their occurrence. Numerous risk factors for inhibitor development have been identified or high throughput screening assay hypothesized, with genetics and environmental considerations combining as crucial contributory components [11,12]. Identification of haemophilic patients with a higher risk of inhibitor formation may allow for individual tailoring of therapy, and thus ensure optimal benefit for patients. In a following article, I discuss the risk factors, with a

particular focus on modifiable conditions such as age at exposure to factor replacement, type of replacement factor used or treatment intensity because their identification as risk factors might be taken into account to define preventive strategies for inhibitor formation. Addressing this issue, I introduce SIPPET, the Survey of Inhibitors in Plasma-Product Exposed Toddlers study, a prospective, randomized trial that aims to evaluate immunogenicity of plasma-derived or recombinant replacement factors while also defining environmental factors for increased risk of inhibitor development [13]. Such a study might provide complementary data to studies drawn from different ongoing selleck chemical cohorts of pups. In patients who have developed inhibitors, immune tolerance induction (ITI) with high doses of FVIII or FIX may allow reinstatement selleckchem of conventional prophylaxis [14]. A substantial proportion of patients (approximately 20–40%) with clinically significant inhibitors do not benefit from ITI therapy [15], and bleeding is controlled with bypassing agents [16]. The article by Professor Manuel Carcao and Dr Thierry Lambert reviews and discusses international experience of using the bypassing agents NovoSeven® [recombinant factor VIIa (rFVIIa); Novo Nordisk, Bagsvaerd, Denmark] and the plasma-derived activated prothrombin

complex concentrate (pd-aPCC) FEIBA® (FVIII inhibitor bypassing activity; Baxter AG, Vienna, Austria) as prophylaxis for patients with haemophilia and inhibitors. Retrospective studies and case reports showing a reduction in joint bleeds and prevention of joint damage with aPCC or rFVIIa prophylaxis are described, and upcoming studies investigating bypassing agents as prophylaxis are introduced. Studies have demonstrated the efficacy and safety of rFVIIa in prophylactic regimens and evidence suggests a prolonged biological effect of rFVIIa [17]; however, the perception remains that the short plasma half-life [18] and consequent need for repeated daily injections could potentially limit its use for long-term prophylaxis [19].