Heparin cofactor II (HCII) (HCII)

Heparin cofactor II (HCII), encoded by the SERPIND1 gene, is a 66 kDa plasma glycoprotein and a member of the serine protease inhibitor (serpin) superfamily. Its primary physiological role is the rapid and specific inactivation of thrombin, the central enzyme in the blood coagulation cascade. Unlike antithrombin, which inhibits multiple coagulation factors, HCII is highly selective for thrombin and is uniquely activated by dermatan sulfate in addition to heparin [1]. This specificity allows HCII to play a critical role in regulating coagulation and thrombin-induced cellular responses particularly in the extravascular compartment and following vascular injury [2]. Clinically, HCII deficiency is associated with an increased risk of atherosclerotic disease, restenosis, and thromboembolic events, suggesting a protective role in cardiovascular health [4]. Therapeutic strategies targeting HCII often utilize dermatan sulfate or specific glycosaminoglycans to achieve localized anticoagulation with a potentially lower systemic bleeding risk compared to traditional heparin therapies.

Other names

Serpin D1SERPIND1Protease inhibitor leuserpin-2HCF2HC2Leuserpin-2

Heparin cofactor II acts as a suicide substrate for thrombin, forming a stable 1:1 covalent complex that irreversibly inhibits the enzyme's procoagulant activity. This inhibitory process is accelerated up to 1000-fold in the presence of glycosaminoglycans such as heparin or dermatan sulfate, which bind to a specific polyanion-binding site on HCII and facilitate its interaction with thrombin [1][2].