Antithrombin (AT) deficiency increases the risk of thrombosis. Current evidence shows that some SERPINC1 mutations responsible for antithrombin deficiency often present a slightly decreased or normal activity and therefore could not be detected by functional tests. This study was designed to compare activity assays and direct genetic analyses in identifying hereditary antithrombin deficiency. In total, 400 consecutive patients with venous thrombosis were enrolled. Functional assays showed that 16 of the 400 individuals had decreased antithrombin activity, and 14 of them were confirmed by genetic analysis. Of the remaining 384 patients, 95 individuals without a known risk factor and 95 individuals with predisposing factors were also selected for gene sequencing. Eight additional causative mutations were identified in nine individuals and they should also be considered as antithrombin deficiency. In addition, a recurrent mutation, p.Arg356_Phe361del, was characterised. The mutant appeared to have a partially impaired secretion and a reduction in functional activity by 50 %. This study indicated that including genetic analysis in screening tests for identifying antithrombin deficiency was essential. Specifically, a genetic analysis of SERPINC1 is strongly recommended when individuals experience unprovoked thrombotic diseases, even if the AT activities are normal.
Keywords: Antithrombin deficiency; activity assay; genetic; mutation; thrombosis.