Assessment of hereditary thrombophilia: Performance of antithrombin (AT) testing

Abstract

Antithrombin (AT) is a naturally occurring plasma inhibitor of coagulation, which is a synthesized in the liver. AT inhibits coagulation serine proteases (the enzymatically activated forms of the clotting factors), mainly thrombin (factor IIa) and factor Xa, but also to a lesser extent factors IXa, XIa, and XIIa. Acting alone, AT inhibits coagulation factors, but does this very slowly; however, when coupled with heparin as a cofactor, the speed of inhibition is increased many fold. The AT/Heparin complex is the most powerful naturally occurring anticoagulant in blood. AT levels of <70% of normal can cause significant thrombosis. Low levels of AT are caused by inherited genetic defects or acquired causes from other disease states. Plasma AT levels can be determined using a chromogenic assay with either bovine thrombin or human factor Xa as the enzyme. The generated color generated in the assay is inversely proportional to the concentration of AT in the plasma.