More than

45% of severe cases are due to inversions involving intrachromosomal homologous recombination between the segmental duplications int22h-1 located in intron 22 of the F8 gene and one of the two duplicons int22h-2 or int22h-3 situated approximately 400 and 500 kb more telomerically. Inversion of click here intron 1 present in 1 to 3% of severe cases is secondary to a similar mechanism between other duplicated sequences. Sequencing of the complete human genome has shown that ~ 5% is composed of duplicated sequences. Several segmental duplications are implicated in many genomic disorders (Charcot-Marie-Tooth, Smith Magenis). Several other duplications represent polymorphisms that are neutral suggesting that they have played a role in the genomic evolution. With respect to HA, besides intron 22 and 1 inversions, the presence of duplicated sequences in the F8 gene and their pathogenic implications have not been studied. Using microarray-based comparative genome hybridization assay, we delimited duplications of the 5’ position of F8 gene (including exons 1 to 22 and exon 1 only) in normal and HA patients harbouring different

severities of HA. The causal effects of the duplications could be explained by different rearrangements inside F8 gene. These findings show that duplications resulting from a recombination between homologous sequences at Xq28 may be present in both learn more normal subjects and HA patients. These duplications may be neutral in function except if they are accompanied by a more complex rearrangement medchemexpress disturbing the F8 gene. LB03 First in human clinical experience of a high purity factor X concentrate MT ALVAREZ1, I FERNANDEZ1, R LUDDINGTON2, M NORTON3 and C DASH3 1Hospital Universitario La Paz, Madrid, Spain; 2Department of Haematology, Addenbrooke’s Hospital, Cambridge, UK; 3Bio Products Laboratory (BPL), Elstree, UK Introduction: Severe factor X deficiency is a rare (1:~1,000,000) and potentially life-threatening bleeding disorder. BPL has developed

a high-purity factor X concentrate (FACTOR X) specifically for the management of this condition. Objectives: To evaluate the pharmacokinetics (PK), safety and efficacy of FACTOR X in patients with severe and moderate hereditary factor X deficiency (<5% normal FX:C). PK parameters for FX:C (one-stage clotting assay) and FX:Ag are assessed at baseline and 6 months post-baseline with sampling timepoints up to 144 hours (6 days) post-infusion. Efficacy in bleed management is assessed over at least 6 months. Results: PK data: Data from the first 2 patients’ baseline FX:C PK profiles give incremental recoveries of 1.64 and 1.92 IU/dL per IU/kg, and half-lives of 25.1 and 39.4 hours (non-compartmental analysis). Efficacy data: One patient has experienced a shoulder haemarthrosis, starting 7 days after the PK dose.