Phenotypic and Genotypic Analysis of a Hereditary Antithrombin Deficiency Pedigree Due to a Novel SERPINC1 Mutation (p.Met281Thr)

Abstract Antithrombin (AT) is one of the physiological anticoagulants that are mainly synthesized in the liver. As a protease inhibitor belonging to the serpin superfamily, AT is able to inactivate thrombin and inhibit activated coagulation factors IX, X, XI, and XII (FIXa, FXa, FXIa, and FXIIa).1 Moreover, it has been found that AT can inhibit activated FVII (FVIIa) by accelerating dissociation of FVIIa–tissue factor complex and preventing it from recombining.2 The AT gene (SERPINC1), located on chromosome 1 at q23.1–23.9 and spreads 13.5 kb, is composed of seven extrons and six introns.3 Hereditary AT deficiency is a rare thrombotic disorder caused by defects in SERPINC1 gene.4 It is inherited in an autosomal-dominant manner with an incidence of roughly 0.02 to 0.25% in the general population and 2 to 5% in patients with a history of venous thromboembolism (VTE).1 5 The most common thrombotic manifestations of patients with AT deficiency are VTEs, and their risks of VTE are approximately 20 times higher than those of nondeficient individuals.6 And the consequences of thrombophilia caused by AT deficiency are more severe than those of protein C and S protein deficiency,2 so it should be given sufficient attention.