In the first phase of life, it is difficult to discriminate the bleeding pattern of a child with a potential inhibitor from that of a child with severe haemophilia without an inhibitor. As a consequence, inhibitor diagnosis moved from clinical suspicion of an inhibitor because of lack of response to treatment and

Pifithrin-�� mw reduced recovery, to routine inhibitor testing up to every 5 exposure days during the first 50 exposure days. We have published several large observational studies regarding inhibitor incidence and have found that overall, more low-titre inhibitors were diagnosed after 2000 [1, 13]. For the purpose of this article, a pooled analysis was done of all patients with severe haemophilia A (FVIII activity < 0.01 IU mL−1), diagnosed between 1990 and 2009 and followed until 50 exposure days. Clinically relevant inhibitor development was determined as at least two positive inhibitor titres and a decreased FVIII recovery (<66%) [15]. Positive inhibitor titres were defined according to the cut-off levels of assays of local laboratories. High-titre inhibitor development was defined as a peak inhibitor titre of ≥ 5 BU mL−1. In total 926 PUPs with severe haemophilia A were included, of whom 322 were diagnosed between 1990 and 2000

and 604 were diagnosed between 2000 and 2009. In the first decade, 上海皓元医药股份有限公司 77 of 322 patients developed inhibitors with a total inhibitor incidence of 24.0%; in the second decade, 182 of 604 patients developed Tamoxifen inhibitors with a total incidence of 30.6%. The difference in incidence is significant (P = 0.035). However, when only high-risk inhibitors are considered, the percentages drop to 19.6% and 20% respectively (not significant). The difference in inhibitor incidence, therefore, can be explained fully by the fact that more low-titre inhibitors are found, increasing from 4.3% between 1990 and 2000 to 10.1% between 2000 and 2009 (P = 0.0002). As the introduction of recombinants

products in the early 1990s, most studies report a higher risk of inhibitors with recombinant products. Several studies and meta-analyses have been performed to enable comparison between the published studies. [2, 16, 17] The first meta-analysis, performed by Wight and Paisley in 2003, clearly identified factors that made comparisons problematic: differences in study designs, small studies and differences in the definition of outcomes. In the most recent meta-analysis, the overall conclusion was that there is no difference in terms of inhibitor development between recombinant and plasma products [18]. There is still data, however, that support differences in inhibitor incidence for individual products [19]. These results need further confirmation.