antithrombin

Antithrombin, also known as antithrombin III, is a small glycoprotein of the serpin family that inhibits several proteases of the coagulation cascade. It is encoded by the SERPINC1 gene and produced mainly by the liver. In plasma, antithrombin prevents clot formation by inactivating thrombin (factor IIa) and factor Xa, and it also targets other serine proteases such as IXa, XIa, XIIa, and kallikrein to a lesser extent.

Antithrombin activity is markedly enhanced by heparin and other sulfated glycosaminoglycans. Binding of heparin induces a conformational change that accelerates the inhibition of coagulation proteases by hundreds to thousands of times, forming stable protease–antithrombin complexes. Endothelial surfaces containing heparan sulfate also support this anticoagulant effect.

Physiologically, antithrombin helps maintain hemostatic balance by restraining coagulation. It has a plasma half-life of about 2–3 days, and levels can be reduced in conditions such as liver disease or nephrotic syndrome, contributing to a prothrombotic state.

Congenital antithrombin deficiency is usually autosomal dominant and increases lifetime risk of venous thromboembolism, particularly with additional risk factors. Acquired reductions occur in liver failure, nephrotic syndrome, disseminated intravascular coagulation, sepsis, or during heparin therapy when resistance occurs due to low antithrombin levels.

Diagnosis typically includes assays of antithrombin activity and antigen. Type I deficiency shows reduced activity and antigen; type II shows normal antigen with reduced activity. Treatment may involve antithrombin concentrates (plasma-derived or recombinant), especially in individuals with hereditary deficiency undergoing surgery or in states of heparin resistance.