Antithrombin activity

The complex orchestration of cellular and molecular participants of haemostasis achieves a crucial yet fine balance of procoagulant and anticoagulant mechanisms. Deficiencies of natural anticoagulant regulators of secondary haemostasis, such as antithrombin, protein C and protein S, and gain of function mutations in genes for FII and FV, are heritable disorders that can shift this balance and increase the risk of venous thromboembolic disease. Antithrombin (AT) is a serine protease inhibitor whose main target enzymes are thrombin and FXa, although it also possesses activity against FIXa, FXIa and TF:FVIIa. It is more efficient at inhibiting free thrombin and FXa than when they are contained within activation assemblies on clot surfaces, thus acting as a scavenger of potentially lethal enzymes that would otherwise diffuse away and cause unnecessary fibrin formation elsewhere. This serves to localise clot formation to the site of injury and limit coagulation. Hereditary AT deficiency can manifest as a reduced concentration of normally functioning AT, (type I defect), or a deficiency of function, (type II defect).