Clinically, congenital AT III deficiency (1:500–5000 incidence) predisposes to venous thromboembolism (VTE), with 85% of carriers experiencing deep vein thrombosis (DVT) or pulmonary embolism (PE) by age 50. Acquired deficiencies arise from hepatic dysfunction, nephrotic syndrome, disseminated intravascular coagulation (DIC), or sepsis. Reduced AT III levels (<80% activity) correlate with hypercoagulability, postoperative thrombosis, and obstetric complications like preeclampsia.

Therapeutically, human plasma-derived AT III concentrates are FDA-approved for hereditary deficiency management and perioperative prophylaxis in high-risk surgeries (e.g., cardiopulmonary bypass, liver transplantation). Emerging applications include adjunct therapy for COVID-19-associated coagulopathy and modulation of inflammatory signaling via endothelial syndecan-4 receptors. AT III monitoring guides anticoagulant dosing in heparin-resistant patients, while novel siRNA therapies targeting hepatic synthesis show promise for thromboprophylaxis.

Common uses include IVD standards, calibrators and controls, proteolytic enzyme studies, and biotherapeutic studies.