antithrombine

Antithrombin is a circulating serine protease inhibitor (serpin) that plays a central role in regulation of blood coagulation. It inactivates several activated coagulation factors, most notably thrombin (factor IIa) and factor Xa, and also inhibits factors IXa, XIa and XIIa. Antithrombin acts by forming stable, irreversible complexes with target proteases; this inhibition is greatly accelerated when antithrombin binds a specific pentasaccharide sequence found in heparin and related glycosaminoglycans.

Antithrombin is a glycoprotein of the serpin family encoded by the SERPINC1 gene. Plasma antithrombin circulates as a single-chain protein of roughly 55–60 kDa. It is primarily synthesized in the liver and is subject to modulation by inflammation, pregnancy, and certain medications.

Clinical relevance includes inherited and acquired antithrombin deficiency, both of which increase the risk of venous thromboembolism. Hereditary deficiency is classified as type I (reduced antigen and activity—quantitative) or type II (normal antigen with reduced activity—qualitative). Acquired reductions can occur with liver disease, nephrotic syndrome, disseminated intravascular coagulation, and during some obstetric complications. Low antithrombin may cause heparin resistance because heparin’s anticoagulant effect depends in part on antithrombin.

Laboratory assessment includes antigen and functional activity assays. Therapeutically, antithrombin concentrates and, less commonly, recombinant products are used in specific deficiency states; management of thrombosis in affected patients follows established anticoagulation guidelines.