antytrombin

Antithrombin, also known as antithrombin III, is a serine protease inhibitor (serpin) produced mainly by the liver and circulating in blood plasma. It functions as a key natural anticoagulant by inhibiting thrombin (factor IIa) and several other proteases in the coagulation cascade, including factor Xa, IXa, XIa, and XIIa. By limiting the activity of these enzymes, antithrombin helps regulate clot formation.

Antithrombin acts by forming stable, inactive complexes with its target proteases. The presence of heparin, a glycosaminoglycan, markedly accelerates this inhibition—often by more than a thousandfold—through a heparin-induced conformational change in antithrombin. Endothelial heparan sulfate and pharmacologic heparins (unfractionated and low-molecular-weight) enhance this effect, increasing the efficiency of coagulation control.

Clinically, inherited antithrombin deficiency is a rare cause of hereditary thrombophilia and raises the risk of venous thromboembolism. Acquired deficiency can occur with liver disease, nephrotic syndrome, disseminated intravascular coagulation, or during pregnancy. Diagnosis relies on assays of antithrombin activity and antigen levels, sometimes complemented by genetic testing. Management may involve administration of plasma-derived or recombinant antithrombin concentrates and careful use of heparin in affected individuals.

Structurally, antithrombin is a ~60 kDa glycoprotein belonging to the serpin family. It is measured clinically by functional activity and antigen tests. In therapeutic contexts, antithrombin concentrates are used to treat hereditary or acquired deficiency states and to optimize anticoagulant therapy when heparin responsiveness is impaired.