Importance of antithrombin evaluation and supplementation in clinical practice

Antithrombin (AT) is a key natural anticoagulant that primarily inhibits thrombin, factor Xa, and other procoagulant proteases, maintaining hemostatic balance. Deficiency in AT, whether inherited or acquired, significantly increases the risk of venous thromboembolism, obstetric complications and sporadically arterial thrombosis. Individuals with AT deficiency are 15 times more likely to develop thrombosis. Acquired deficiency is more common and may result from hypoproduction, excessive excretion or loss, increased consumption, or dilution of AT. In critically ill patients, acquired antithrombin deficiency may occur frequently; however, routine monitoring of antithrombin levels is not currently supported by strong evidence and should be reserved for selected clinical indications, especially with risk of thromboembolism. Antithrombin is essential for the action of unfractionated heparin, low-molecular-weight heparin, and fondaparinux, meaning deficiency can lead to resistance to these anticoagulants. Antithrombin deficiency is often detected in cases of resistance during the administration of antithrombin-dependent anticoagulants, typically indicated by insufficient levels of anti-Xa activity. Supplementation of AT is indicated for preventing and treating thrombotic events in patients with congenital or acquired AT deficiencies. Supratherapeutic antithrombin levels during heparin therapy can lead to bleeding. Its role in thromboembolism, anticoagulant resistance, and pleiotropic effects highlights its clinical importance and research potential.