Antitrombine

Antithrombin, also known as antithrombin III, is a small glycoprotein and a key serine protease inhibitor (serpin) produced mainly by the liver and circulating in blood plasma. It acts as a natural anticoagulant by inhibiting several enzymes in the coagulation cascade, most notably thrombin (factor IIa) and factor Xa, with additional activity against factors IXa, XIa, and XIIa.

The inhibitory mechanism of antithrombin is enhanced in the presence of heparin or other negatively charged polysaccharides. When heparin binds to antithrombin, the rate of inactivation of target proteases increases dramatically (often by orders of magnitude), enabling anticoagulation at lower concentrations of thrombin and other enzymes.

Clinically, antithrombin activity can be reduced due to inherited or acquired conditions. Hereditary antithrombin deficiency is a rare thrombophilia that increases the risk of venous thromboembolism, typically in deep vein thrombosis or pulmonary embolism. It is classified as a quantitative deficiency (lower levels of antithrombin) or a functional deficiency (antithrombin present but impaired). Acquired decreases can occur with liver disease, nephrotic syndrome, disseminated intravascular coagulation, or severe consumption. Antithrombin levels and activity can be measured by functional assays (antithrombin activity) and antigen-based tests.

Treatment considerations include replacement therapy with antithrombin concentrates, derived from plasma or produced via recombinant methods, to restore anticoagulant activity in individuals with deficiency, particularly around surgical procedures or during pregnancy, or when heparin therapy requires augmentation. In routine care, anticoagulation decisions also depend on the overall risk profile and coexisting conditions.