SERPINC1-mediated hereditary antithrombin deficiency with refractory pulmonary embolism: successful treatment with VA-ECMO and interventional thrombus aspiration

Abstract

Venous thromboembolism (VTE) carries substantial global morbidity and mortality, with 50%–60% of disease variability attributed to genetic factors. Hereditary antithrombin deficiency (HATD), caused by pathogenic variants in the SERPINC1 gene, is an autosomal dominant thrombophilia that confers a 20–40-fold higher risk of VTE, predominantly manifesting as recurrent pulmonary embolism (PE) and deep vein thrombosis (DVT). We report a 22-year-old male with recurrent PE secondary to type II HATD driven by a heterozygous SERPINC1 missense variant (c.1315 C > A, p.Pro439Thr). His second episode of PE progressed to obstructive cardiogenic shock refractory to systemic thrombolysis, accompanied by hemoptysis. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was initiated, yet recurrent oxygenator thrombosis occurred despite high-dose unfractionated heparin (UFH) infusion. Laboratory testing revealed an antithrombin III (AT-III) activity level of 39.5%, confirming the diagnosis. Pulmonary angiography followed by mechanical thrombus aspiration was performed, and long-term anticoagulation was switched to rivaroxaban. The patient was successfully weaned from VA-ECMO, with no PE recurrence or adverse cardiovascular events recorded during 5 years of follow-up. This case represents the first published report of a young patient with a SERPINC1 variant complicated by recurrent high-risk PE unresponsive to rt-PA thrombolysis who survived after VA-ECMO-supported pulmonary thrombus aspiration. Early etiological genetic screening for hereditary thrombophilia is essential for managing refractory PE induced by SERPINC1 variants. Individualized regimens combining VA-ECMO, interventional thrombectomy, and direct oral anticoagulants (DOACs) yield favorable clinical outcomes and provide a reference for managing critically ill patients with hereditary thrombophilia.