Molecular and Biological Characterization of Transient Antithrombin Deficiency: A New Concept in Congenital Thrombophilia

Antithrombin deficiency, mainly but not exclusively due to SERPINC1 gene variants, is a major thrombophilia that is significantly associated to early-onset venous thromboembolism. The diagnostic algorithm of antithrombin deficiency relies on the classical biochemical-molecular sequence, adopted for all thrombophilic states. Therefore, genetic analysis of SERPINC1 is restricted to cases with confirmed antithrombin deficiency, that is, cases with at least two positive findings by using functional assays or with other relatives carrying this disorder. This strategy has enabled the identification of gene variants in up to 80% of cases with antithrombin deficiency and rendered plenty of both biochemical and genetic knowledge about antithrombin. Furthermore, defects of N-glycosylation underlie a proportion of cases with antithrombin deficiency that is not explained by SERPINC1 variants.