Hereditary thrombophilia due to congenital antithrombin deficiency

Hereditary thrombophilia due to congenital antithrombin deficiency is a rare inherited blood clotting disorder caused by mutations in the SERPINC1 gene, which encodes antithrombin (formerly known as antithrombin III). Antithrombin is a natural anticoagulant protein that plays a critical role in regulating blood clot formation by inhibiting thrombin and other activated clotting factors. When antithrombin levels or function are reduced, the balance between clot formation and clot prevention is disrupted, leading to an increased tendency to form abnormal blood clots (thrombophilia). The condition is also known as antithrombin III deficiency or hereditary antithrombin deficiency. The disease primarily affects the vascular system, with patients at significantly increased risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) — most commonly in the legs — and pulmonary embolism. Thrombotic events can also occur in unusual sites such as mesenteric, cerebral, or portal veins. The first thrombotic episode typically occurs in young adulthood, often triggered by additional risk factors such as surgery, pregnancy, oral contraceptive use, immobilization, or trauma. Congenital antithrombin deficiency is considered one of the most severe inherited thrombophilias, with a higher lifetime risk of thrombosis compared to other hereditary thrombophilias such as Factor V Leiden or prothrombin gene mutations. Two main types exist: Type I (quantitative deficiency with reduced antithrombin levels) and Type II (qualitative deficiency with dysfunctional antithrombin protein at normal or near-normal levels). Treatment focuses on prevention and management of thrombotic events. Acute thrombosis is treated with anticoagulation therapy, typically heparin followed by long-term oral anticoagulants such as warfarin or direct oral anticoagulants. Antithrombin concentrate (plasma-derived or recombinant) may be administered in high-risk situations such as surgery, childbirth, or acute thrombosis, particularly when heparin resistance is encountered. Long-term or lifelong anticoagulation may be recommended for patients with recurrent thrombotic events. Genetic counseling is advised for affected families. Homozygous Type I deficiency is generally considered incompatible with life, while homozygous Type II deficiency (particularly the heparin-binding site subtype) can present with severe neonatal or childhood thrombosis.

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