Description

• Antithrombin is a protease that inhibits thrombin by forming an irreversible thrombin–antithrombin complex.
• There are 2 active sites: One that binds to heparin and one that binds to thrombin/target enzyme. Antithrombin can also inhibit factors Xa, IXa, and XIa. This process is catalyzed by the presence of heparin.
• Patients deficient in antithrombin have an increased incidence of venous thrombosis, including deep vein thrombosis (DVT) of the lower extremity. Arterial thrombosis is much less common in patients deficient in antithrombin.

• System(s) affected: Cardiovascular; Nervous; Pulmonary; Reproductive; Hemic/Lymphatic/Immunologic
• Synonym(s): Antithrombin III deficiency

Epidemiology

• Predominant age: Mean age of first thrombosis is in 2nd decade, mainly after puberty
• Predominant sex: Male = Female

Incidence
4% of patients with thrombophilia

Prevalence
0.16% of normal individuals

Risk Factors

• Oral contraceptives, pregnancy, and the use of hormone replacement therapy (HRT) increase the risk of venous thrombosis in patients with antithrombin deficiency.
• Patients with antithrombin deficiency and another prothrombotic state, such as factor V Leiden or the prothrombin 20210 mutation, have increased rates of thrombosis.
• Heterozygotes have an odds ratio of venous thrombosis of 10–20.

Pregnancy Considerations
Increases thrombotic risk in patients with antithrombin deficiency, especially when complicated by HTN, preeclampsia, or eclampsia.

Genetics
Autosomal dominant

General Prevention

Patients with antithrombin deficiency without a history of thrombosis do not require prophylactic treatment.

Pathophysiology

• Type I deficiency is characterized by low levels of antigen. Type II deficiency is found when the antithrombin molecule is dysfunctional.
• Type II deficiencies are due to mutations in either the active center of antithrombin that binds the target enzyme or the heparin-binding site.
• No patients homozygous for defects in the active center have been described, suggesting that this is a lethal condition. Patients heterozygous for mutations in the heparin-binding site rarely have thrombotic episodes.

Etiology

Many mutations in the antithrombin gene have been identified.

Commonly Associated Conditions

Venous thromboembolism