title: p.Tyr365Cys change in factor VIII: haemophilia A, but not as we know it.
abstract: Haemophilia A is caused by a reduction in clotting factor VIII (FVIII). FVIII coagulant activity (FVIII:C) can be measured by three methods; the one-stage activated partial thromboplastin time-based clotting assay, the two-stage Xa generation-based clotting assay and the chromogenic Xa generation-based assay. The FVIII:C of most patients with haemophilia A are concordant regardless of the assay method employed. Up to a third of patients show assay discrepancy, usually with the two-stage and chromogenic assays being much lower than the one-stage assay. Very rarely, patients have been reported with lower one-stage compared to two-stage and chromogenic assays, but here we report that the mutation p.Tyr365Cys accounts for most of these patients and, at least in the UK, is not rare. We have identified this mutation in 23 different families. Affected male index individuals had a lower mean one-stage FVIII:C of 27 iu/dl compared to two-stage FVIII:C mean of 77 iu/dl. Affected individuals had minimal or absent bleeding symptoms and when these were present they were usually in patients with another co-inherited bleeding disorder. Affected individuals often had surgery without the need to correct the one-stage FVIII:C.
authors.affiliation: Sheffield Haemophilia and Thrombosis Centre, University of Sheffield, Sheffield, UK.
authors.forename: Annette E
authors.initials: AE
authors.lastname: Bowyer
authors.forename: Anne
authors.initials: A
authors.lastname: Goodeve
authors.forename: Ri
authors.initials: R
authors.lastname: Liesner
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Mumford
authors.forename: Steve
authors.initials: S
authors.lastname: Kitchen
authors.forename: Mike
authors.initials: M
authors.lastname: Makris
mesh_terms: D001777:Blood Coagulation / Q000235:genetics; D005169:Factor VIII / Q000235:genetics*; D005190:Family; D005260:Female; D006467:Hemophilia A / Q000453:epidemiology / Q000235:genetics*; D006470:Hemorrhage / Q000235:genetics; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D006113:United Kingdom
chemical_list: D005169:Factor VIII