title: The incidence of dysfunctional antithrombin variants: four cases in 210 patients with thromboembolic disease.
abstract: 210 patients, with a history of venous thrombosis, have undergone prothrombotic investigations. In nine cases a consistent deficiency of antithrombin was identified. In five there was a reduction in the plasma antigenic concentration of antithrombin and in a further four cases deficiency was due to the presence of a dysfunctional antithrombin variant. The variants have all been characterized by DNA analysis and in three the mutations have been confirmed by peptide sequencing (antithrombin Basel (41 Pro to Leu). Hamilton (382 Ala to Thr). Cambridge I (384 Ala to Pro) and Cambridge II (384 Ala to Ser). The incidence of antithrombin deficiency in patients with a history of venous thrombosis has previously been quoted at between 2% and 3%: there is no published data available on the incidence of antithrombin variants. In our series 5% of patients who presented before the age of 40 years had antithrombin deficiency, and 2% of the total number of patients investigated had a dysfunctional variant. Our figures indicate that a significant number of cases of antithrombin deficiency are due to dysfunctional variants and that the true incidence of antithrombin deficiency in patients with a history of venous thrombosis is in the order of 5%.
authors.affiliation: Department of Haematology, University of Cambridge.
authors.forename: P L
authors.initials: PL
authors.lastname: Harper
authors.forename: R J
authors.initials: RJ
authors.lastname: Luddington
authors.forename: M
authors.initials: M
authors.lastname: Daly
authors.forename: D
authors.initials: D
authors.lastname: Bruce
authors.forename: D
authors.initials: D
authors.lastname: Williamson
authors.forename: P F
authors.initials: PF
authors.lastname: Edgar
authors.forename: D J
authors.initials: DJ
authors.lastname: Perry
authors.forename: R W
authors.initials: RW
authors.lastname: Carrell
mesh_terms: D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000235:genetics / Q000502:physiology*; D020152:Antithrombin III Deficiency; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011655:Pulmonary Embolism / Q000097:blood*; D013924:Thrombophlebitis / Q000097:blood*
chemical_list: D000990:Antithrombin III