Familial onset of venous thromboembolism due to inherited antithrombin deficiency with a novel gene variant (p.Arg14Gly)

Abstract

Inherited antithrombin deficiency is an autosomal dominant thrombophilia, resulting from genetic variations in the serpin family C member 1 (SERPINC1) gene. Antithrombin deficiency increases the risk of venous thromboembolism (VTE) compared to the general population. In this report, a novel missense variant of SERPINC1, c.40A>G, p.Arg14Gly that predicts to cause secretion defect of antithrombin, was identified in two related patients: a 65-year-old man with chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism, and his son with early onset of VTE. Treatment with direct oral anticoagulants and catheter interventions led to successful outcomes for both patients. These cases highlight the importance of screening testing for inherited antithrombin deficiency and intrafamilial survey in patients with VTE and CTEPH.

Learning objectives: Inherited antithrombin deficiency is associated with a strong risk of venous thromboembolism (VTE). However, the relationship between inherited antithrombin deficiency and chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. The influence of antithrombin deficiency on developing CTEPH following acute pulmonary embolism requires further investigation. This report emphasizes the importance of screening for thrombophilic factors in cases of VTE and CTEPH.

Keywords: Balloon pulmonary angioplasty; Catheter-directed thrombolysis; Chronic thromboembolic pulmonary hypertension; Genetic variant; Inherited antithrombin deficiency; Venous thromboembolism.