Heparin Cofactor II


Molecular mass65.000 Da
Plasma concentration80 mg/l, 1.2 μmol/l
Normal range60 - 170%

Heparin Cofactor II (HC II) is a specific thrombin inhibitor and, in contrast to antithrombin, does not inhibit factor Xa. HC II can thus influence antithrombin assays using thrombin. In contrast, test methods in which factor Xa is used, specifically determine the antithrombin activity, the complex formation between HC II and thrombin is considerably accelerated by heparin and dermatan sulphate. In vivo, HCII becomes active only when the antithrombin concentration has decreased below 30%. It seems likely that HC II is of significance as a thrombin inhibitor in the extra vascular area following injury. This is supported by the increased inhibition through dermatan sulphate, which is only found in the extra vascular space.

Clinical significance

Hereditary heparin cofactor II deficiency correlates with increased risk for thrombosis. An acquired deficiency is observed in liver disease, diabetes mellitus and in DIC. Increased heparin cofactor II concentrations have been detected following use of oral contraceptives, during pregnancy and with increasing age.


  • Suspected heparin cofactor II deficiency
  • Diagnosis of thrombotic risk factors


  1. Tollefsen DM et al. Heparin cofactor II. J Biol Chem 257, 2162-2169, 1982.
  2. Tran TH, Duckert F. Influence of heparin cofactor II (HCII) on the determination of antithrombin III (AT). Thromb Res 40, 571-576, 1985.
  3. Struß D et al. The inhibition of thrombin and chymotrypsin by heparin cofactor II. Thromb Res 68, 45-56, 1992.
  4. Tollefsen DM. Laboratory diagnosis of antithrombin and heparin cofactor II deficiency. Sem Thromb Haemost 16, 162-168, 1990.
  5. Tran TH, Duckert F. Heparin cofactor II determination - Levels in normals and patients with hereditary antithrombin III deficiency and disseminated intravascular coagulation. Thromb Haemost 52, 112-116, 1984.
  6. Toulon P. Increased heparin cofactor II levels in women taking oral contraceptives. Thromb Haemost 64, 365-368, 1990.
  7. Mackie IJ et al. Heparin cofactor II levels are increased by the use of combined oral contraceptives. Blood Coag Fibrinol 1, 647-651, 1990.
  8. Saito A. Heparin cofactor II is degraded by heparan sulfate and dextran sulfate. Biochem Biophys Res Commun. Feb 20, 457(4), 585-8, 2015.
  9. Kumar A, Bhandari A, Sarde SJ, Goswami C. Genetic variants and evolutionary analyses of heparin cofactor II. Immunobiolo-gy. Sep 219(9), 713-28, 2014.

Test kits

Chromogenic Assay

UNITEST Heparin Cofactor II

Matched-Pair Antibody sets

ELISA Heparin Cofactor II

ELISA Thrombin-Heparin Cofactor II-Complex