antitrombin

Antithrombin, also called antithrombin III, is a small plasma glycoprotein and a member of the serine protease inhibitor (SERPIN) family. It regulates blood coagulation by inhibiting several serine proteases in the coagulation cascade, most effectively thrombin (factor IIa) and factor Xa, and to a lesser extent factors IXa, XIa, and XIIa. Inhibitory action occurs through formation of irreversible complexes with active enzymes. Antithrombin activity is dramatically enhanced by binding to heparin in the bloodstream or to heparan sulfate on endothelial cells, which induces a conformational change that speeds inhibition by up to several thousand-fold.

Antithrombin is produced mainly by the liver and circulates in plasma. Deficiency can be inherited or acquired. Hereditary antithrombin deficiency is rare and can be quantitative (type I) or qualitative (type II). Acquired deficiencies may occur in liver disease, nephrotic syndrome, disseminated intravascular coagulation, or during certain critical illnesses. Measuring antithrombin activity, sometimes alongside antigen level, helps diagnose deficiency.

Clinically, low antithrombin activity predisposes to venous thromboembolism, particularly during pregnancy, after surgery, or when other risk factors are present. Antithrombin concentrates (plasma-derived or recombinant) are used to raise AT activity in patients with deficiency or in those with heparin resistance, to restore effective anticoagulation. Fresh frozen plasma provides a source of antithrombin when specific concentrates are not available. Therapeutic use is common in perioperative settings such as liver transplantation or cardiopulmonary bypass.