Antithrombin III (ATIII) and Heparin cofactor II (HCII) (ATIII and HCII)

Antithrombin III (ATIII) and Heparin Cofactor II (HCII) are essential endogenous anticoagulants belonging to the serpin superfamily that regulate the coagulation cascade by neutralizing serine proteases. ATIII is the primary inhibitor of thrombin (Factor IIa) and Factor Xa, while HCII serves as a secondary, specific inhibitor of thrombin, particularly in the presence of certain glycosaminoglycans (UniProt, 2024). The inhibitory activity of both proteins is dramatically accelerated—up to 1,000 to 10,000-fold—by the binding of heparin, which induces a conformational change in the inhibitors and provides a catalytic surface for the protease-inhibitor interaction (StatPearls, 2023). This dual-inhibitory pathway is the primary pharmacological target of unfractionated heparin (UFH), which is used clinically to prevent and treat thromboembolic disorders such as deep vein thrombosis and pulmonary embolism (PubMed, 2022). While ATIII deficiency is a well-recognized risk factor for hereditary thrombophilia, HCII also contributes to vascular protection and the prevention of arterial thrombosis (NIH, 2023). Drugs targeting this system must be carefully monitored due to the risk of major bleeding and immune-mediated complications like heparin-induced thrombocytopenia (HIT).

Other names

SERPINC1SERPIND1AntithrombinHeparin cofactor 2HCF2AT3

Potentiation of endogenous serine protease inhibitors (Antithrombin III and Heparin cofactor II) to accelerate the neutralization of procoagulant enzymes Thrombin (IIa) and Factor Xa.