Introduction. Antithrombin is a serpin that inhibits multiple procoagulant serine proteases and acts as an endogenous anticoagulant. Thus, congenital antithrombin deficiency constitutes a major thrombophilic state, the most severe so far. Areas covered. In the present work, we globally review the biology, genetics, diagnosis, and management of congenital antithrombin deficiency, and also discuss puzzling questions and future perspectives regarding this severe inherited thrombophilia. Expert opinion. Although this disorder exerts high clinical heterogeneity, many carriers will need careful and long-term anticoagulation and/or thromboprophylaxis, especially in high-risk situations, such as surgery and pregnancy. Notably, antithrombin concentrates constitute a considerable arsenal for both treatment and prevention of acute venous thrombosis in subjects with antithrombin deficiency. Current evidences are based almost exclusively on retrospective case series, so an integrated functional, biochemical and molecular characterization will be of clinical relevance and guide hematologists' personalized decisions.
Keywords: Anticoagulation; antithrombin concentrates; antithrombin deficiency; heparin resistance; inherited thrombophilia; molecular spectrum; pediatric thrombosis; thrombophilia testing; thrombosis during pregnancy; venous thromboembolism.