Clinical Information

Heparin cofactor II is a glycoprotein that belongs to the serine protease inhibitor family. Heparin cofactor II, also known as heparin cofactor A or dermatan sulfate cofactor, has a molecular weight of approximately 65 kilodaltons and has a plasma concentration of 9 mg/dL. Heparin cofactor II is synthesized by the liver and has a plasma half-life of 60 hours. Heparin cofactor II specifically inhibits thrombin, in contrast to antithrombin, which inhibits thrombin, factor Xa, and other serine proteases. The inhibition of thrombin by heparin cofactor II is approximately 10 times slower than antithrombin-mediated inhibition and occurs through the formation of equimolar complexes between the reactive site of the inhibitor and the active site of thrombin. The antithrombotic activity of heparin cofactor II is greatly enhanced (over 1000-fold) in the presence of heparin and dermatan sulfate. The physiologic function of the molecule is unclear, but its role may be to serve as an antithrombotic agent in the presence of dermatan sulfate. Acquired deficiencies of heparin cofactor II are reported in patients with liver disease and disseminated intravascular coagulation. Conversely, increased levels of heparin cofactor II may be observed in individuals with renal disorders with proteinuria, during pregnancy, and with oral contraceptive usage. Inherited deficiency of heparin cofactor II has been reported in rare instances and is inherited as an autosomal dominant trait. A clear relationship between increased risk of thrombosis and heparin cofactor II deficiency has not been established since deficiency of heparin cofactor II is observed in both healthy individuals and those with thrombotic episodes. Limited studies have shown that heterozygosity for heparin cofactor II is not a likely risk for thrombosis without other concomitant risk factors. Other studies have reported thrombotic episodes in 36% of individuals with the deficiency.