There were 395 rFVIIa-treated

procedures (261 surgical, 89 dental and 45 other medical procedures) reported for 263 congenital haemophilia patients with inhibitors. In trials, initial rFVIIa dosing was 35–90 mcg kg−1 bolus injection or 50 mcg kg−1 h−1 continuous infusion. Dosing in the registries and literature was more variable. Recombinant FVIIa effectiveness was comparable across data sources, with an overall rate of 84% (333/395). The incidence of thrombotic events was very low (0.4% of patients and 0.025% of procedures). Prior to the US approval of rFVIIa 5-Fluoracil in 1999, surgical procedures in congenital haemophilia patients with inhibitors were often considered too risky. Recombinant FVIIa has consistently demonstrated effectiveness in treatment of bleeding in these patients during such procedures. Thrombotic events were rare. This analysis confirms the value of corroborating clinical trial results with post-marketing BGB324 surveillance registries to assess small patient populations with clinically challenging management

decisions. “
“Development of inhibitory antibodies is perhaps the most serious complication of FVIII replacement therapy, precluding efficient clinical management of patients with haemophilia A (HA). The development and function of immune system are also regulated by microRNAs (miRNAs). Mutations and changes in the level of expression of some miRNA genes have been

associated with the onset and progression of immunological disorders. The aim of this study was to investigate new genetic polymorphisms in loci for miRNA and check details their targets to evaluate whether these SNPs may confer susceptibility to inhibitor development in patients with HA. Italian HA patients with and without inhibitors and healthy controls were recruited in this study. For SNP analysis, standard DNA sequencing method was used. We have studied four SNPs, i.e. rs36101366, rs34683807, rs1803603 and rs3024496 located in the 3′UTR of F8 and IL-10 genes. These SNPs have been checked for their frequencies in patients with and without inhibitors, but no statistically significant differences were found. Then, we have searched for other genetic variants in loci for haematopoietic-specific miRNAs, i.e. hsa-mir-150, hsa-mir-155, hsa-mir-146a, hsa-mir-142, hsa-mir-181a and in a specific miRNA, hsa-mir-1184, i.e. predicted to be located in the intron 22 of F8 gene. For all miRNAs selected, we did not identify any sequence variation in our study population. This is the first study to demonstrate that there was no association between selected SNPs in miRNAs and their targets and the susceptibility to inhibitor development in people affected by HA. “
“Summary.  Free foetal DNA in maternal blood during early pregnancy is an ideal source of foetal genetic material for non-invasive prenatal diagnosis.