Antithrombin III deficiency

Antithrombin III deficiency is a condition in which the body has too little antithrombin III, a protein that normally helps prevent blood clots. The deficiency can be either inherited or acquired. Inherited cases are rare and usually follow an autosomal dominant pattern, though a few recessive forms exist. The disorder often becomes apparent when a patient experiences repeated venous thromboses, pulmonary embolisms, or recurrent intrauterine fetal death. The increased clotting tendency from hereditary deficiency raises the risk of venous thrombosis. Acquired causes are generally easier to identify than inherited ones.

The condition affects an estimated 0.02% to 0.2% of the general population and is found in 1% to 5% of patients with venous thromboembolism. About half of individuals with antithrombin deficiency will have had a venous thromboembolism by age 50.

A clinical suspicion of antithrombin deficiency may arise in patients with recurrent venous thromboembolism, thrombosis in childhood, or thrombosis during pregnancy. Testing for antithrombin activity can confirm the diagnosis if levels fall below 70%. Deficiency may stem from genetic mutations in the SERPINC1 gene or from acquired factors such as acute thrombosis, disseminated intravascular coagulopathy, liver disease, nephrotic syndrome, L-asparaginase therapy, oral contraceptives, or estrogens. Genetic testing can further evaluate SERPINC1 abnormalities.

Management can be complicated by resistance to unfractionated heparin, particularly with continuous infusions. Resistance is suggested if large daily doses—over 35,000 units—are needed. Antithrombin concentrates are sometimes used, but they carry a bleeding risk when combined with high doses of unfractionated heparin. Full weight-based dosing of low molecular weight heparin is effective, though peak anti-Xa measurements may not accurately reflect the anticoagulant effect. Vitamin K antagonists and direct oral anticoagulants (including anti-Xa inhibitors and thrombin inhibitors) have also been used, but supporting data are limited.