Seventeen novel SERPINC1 variants causing hereditary antithrombin deficiency in a Czech population

Antithrombin (AT) as a serpin is a plasma inhibitor especially of thrombin and factor Xa [ [1] Abildgaard U. Binding of thrombin to antithrombin III. Scand. J. Clin. Lab. Invest. 2004; 64: 659-665https://doi.org/10.3109/00365516909080127 Crossref PubMed Scopus (91) Google Scholar ]. AT deficiency (ATD) as an autosomal dominant disease is an important cause of inherited thrombophilia [ [2] Alhenc-Gelas M. Plu-Bureau G. Hugon-Rodin J. Picard V. Horellou M.-H. GFHT study group on Genetic Thrombophilia, Thrombotic risk according to SERPINC1 genotype in a large cohort of subjects with antithrombin inherited deficiency. Thromb. Haemost. 2017; 117: 1040-1051https://doi.org/10.1160/TH16-08-0635 Crossref PubMed Scopus (24) Google Scholar ]. Its prevalence in the general population is estimated at 0.02%–0.2%; in individuals with venous thromboembolism (VTE), 1%–7%. Thus, the relative risk of a first VTE episode is increased 16-fold compared with the controls. It is the most substantial increase of VTE risk in comparison with other inherited thrombophilias, such as protein C and S deficiencies, factor 5 c.1601G>A and factor 2 c.*97G>A mutations (referred to as factor V Leiden, prothrombin G20210A).