Antithrombin (AT) Activity

The Antithrombin (AT) Activity test—also referred to as antithrombin III activity or heparin cofactor activity—helps confirm and delineate congenital or acquired antithrombin deficiency. Functional activity is assessed first to establish whether values fall within the reference interval before proceeding to antithrombin antigen measurement to distinguish type I (quantitative) from type II (qualitative) patterns. This assay is incorporated into thrombophilia evaluations, the diagnostic workup of venous thromboembolism, and the investigation of heparin resistance when unusually high heparin doses are required to achieve target anticoagulation.

Endothelial cells and hepatocytes are the principal sources of antithrombin. It tempers coagulation by neutralizing thrombin and the activated factors Xa, IXa, and XIa, thereby limiting propagation of clot formation. Hereditary antithrombin deficiency is uncommon, affecting approximately 1 in 5000 individuals, and confers a predisposition to recurrent thrombosis, with initial events frequently occurring in early adulthood. Type I deficiency reflects reduced protein concentration, whereas type II represents a functional defect with normal antigen levels. Antithrombin activity can also be decreased in acquired conditions, including hepatic dysfunction, nephrotic syndrome, disseminated intravascular coagulation, major surgery, extensive thrombosis, marked blood loss, malignancy, prolonged heparin exposure, and high-dose oral contraceptive use. Clinically, insufficient antithrombin is associated with recurrent venous and arterial thrombotic events; in hereditary deficiency, myocardial infarction and stroke may occur at a young age.