Phenotype and molecular genetics of factor XI deficiency in the United Kingdom

A new bleeding disorder was described in 1953 in which the bleeding symptoms were present in both males and females. It was differentiated from haemophilia A and B by plasma mixing studies. Early clinical and family studies of this disorder, factor XI deficiency, were limited to a small number of families, some described before a reliable factor XI:C assay was developed. In 1985 a study was made of 24 families with factor XI deficiency in North London, . followed by a more extensive study of 30 families in North West England. These two studies confirmed the mode of inheritance (autosomal) but demonstrated clearly that r / some individuals (between 30 and 50%) with partial deficiency (heterozygotes) are at risk of bleeding after surgery, particularly in areas high in fibrinolytic activity. The • bleeding tendency is unpredictable and variable, and the second study examined the relationship with other factors which might playa role (von Willebrand factor, which probably does, and factor VII, which does not). Bleeding risk is an important consideration because clinicians must decide whether or not to replace factor XI before and after surgical procedures. A factor XI concentrate became available from 1985 and analysis of clinical and laboratory data reported here Supplied by The British Library - 'The world's knowledge' demonstrated its effectiveness. However it became apparent that this was associated with a thrombotic risk in patients with predisposing factors. The treatment options for managing factor XI deficiency are reviewed in detail, and guidelines were issued to clinicians in the UK. Following identification of the gene sequence for factor XI, work proceeded to identify the causative mutations in these and other UK families. Jewish patients generally have two common mutations, but in the non-Jewish patients we identified new mutations, in particular C128X was found in several families who all share a common haplotype indicating a founder effect.EThOS - Electronic Theses Online ServiceGBUnited Kingdo