Antithrombin III is a powerful inactivator of thrombin and other activating coagulation factors (X, VIII, IX, and XIII). Deficiency of antithrombin III may be inherited, and two-thirds of persons affected have a deep venous thrombosis event by age 35 with or without pulmonary embolism. Antithrombin III deficiency can also be acquired. Causes are acute thrombosis, disseminated intravascular coagulation (bleeding due to deficiency in clotting factors), liver disease, nephrotic syndrome (defects in capillaries extending from kidney tubules), oral contraceptive use, and, rarely, heparin administration.

The preferred test to determine antithrombin III deficiency is the antithrombin-heparin cofactor assay.

Lifelong warfarin therapy is the treatment for people with symptoms of antithrombin III deficiency. People without symptoms are treated only if they have an increased risk of thrombosis, as in pregnancy and during a preoperative period.

Carriers of a mutation of the prothrombin gene (precursor of thrombin) have twice the risk of venous thrombosis that noncarriers do.

A decrease in fibrinolytic (clot-dissolving) activity can result from decreased or abnormal levels of plasminogen activator activity or from increased plasminogen inhibitor activity.