Antytrombiny

Antytrombiny, commonly referred to as antithrombins, are a group of serine protease inhibitors that regulate the coagulation system by inactivating several activated coagulation enzymes. The principal human antithrombin is antithrombin III (ATIII), a liver-produced glycoprotein that primarily inhibits thrombin (factor IIa) and factor Xa, with additional activity against factors IXa, XIa, and XIIa. ATIII belongs to the serpin (serine protease inhibitor) superfamily, and its anticoagulant activity is markedly enhanced by binding to heparin or heparan sulfate on endothelial surfaces.

Mechanism and physiological role: ATIII forms stable complexes with active coagulation proteases, preventing further proteolysis and clot formation. Heparin and related glycosaminoglycans accelerate this inhibition by inducing a conformational change in ATIII, increasing the rate of inactivation by up to several thousand-fold. This interaction underlies the clinical use of heparin as an anticoagulant and explains why antithrombin deficiencies can impair heparin efficacy.

Clinical significance: Congenital AT deficiency is a hereditary risk factor for venous thromboembolism and is typically inherited in an autosomal dominant pattern. It can be quantitative (type I) or qualitative (type II). Acquired AT deficiency occurs in liver disease, nephrotic syndrome, disseminated intravascular coagulation, or during certain illnesses and therapies. In patients with AT deficiency, heparin therapy may be less effective, and treatment may require AT concentrates or fresh frozen plasma to restore antithrombin levels.

Diagnostics and management: Laboratory assessment includes functional antithrombin activity and antigen tests, with results expressed as a percentage of normal. Management focuses on correcting AT deficiency when clinically indicated, especially in surgical or high-risk scenarios, and on selecting anticoagulation strategies mindful of AT status.