Antithrombin III deficiency
A rare clotting disorder causing recurrent venous thrombosis and pulmonary embolism.
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.
- first described
- 1965 by Egeberg
- inheritance
- Usually autosomal dominant; rare recessive cases noted
- prevalence in general population
- ~0.02 to 0.2%
- prevalence in venous thromboembolism pat
- 1-5%
- risk of thrombosis by age 50
- 50% of patients have venous thromboembolism
- diagnostic threshold
- Antithrombin activity less than 70%
- associated gene
- SERPINC1
Lore & Background
Antithrombin III deficiency was first described by Egeberg in 1965. It is a rare hereditary disorder that generally comes to light when a patient suffers recurrent venous thrombosis and pulmonary embolism, and repetitive intrauterine fetal death. Hereditary antithrombin deficiency results in a state of increased coagulation which may lead to venous thrombosis. Inheritance is usually autosomal dominant, though a few recessive cases have been noted.
Reader's Guide
Antithrombin III deficiency is significant as a hereditary thrombophilia that increases the risk of venous thromboembolism, with 50% of affected patients experiencing such events by age 50. Its prevalence is estimated at 0.02 to 0.2% of the general population and 1-5% of patients with venous thromboembolism. Diagnosis relies on clinical suspicion in cases of recurrent venous thromboembolic disease, childhood thrombosis, or thrombosis in pregnancy, confirmed by antithrombin activity levels below 70%. Acquired causes, such as acute thrombosis, liver disease, nephrotic syndrome, or use of oral contraception, must be ruled out. Management is complicated by potential resistance to unfractionated heparin, requiring large doses (over 35,000 units per day) or alternative therapies like low molecular weight heparin, vitamin K antagonists, or direct oral anticoagulants, though data on the latter are limited. Antithrombin concentrates are used but carry bleeding risk with high heparin doses. The condition underscores the importance of identifying both hereditary and acquired causes in thrombotic patients.
Did You Know?
- The disorder was first described by Egeberg in 1965.
- Hereditary antithrombin deficiency is usually inherited in an autosomal dominant pattern.
- Testing for antithrombin activity can confirm deficiency if levels are less than 70%.
- Patients may develop resistance to unfractionated heparin, especially with continuous infusions.
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