Activation of heparin cofactor II by heparin and dermatan sulfate.

ABSTRACT

Heparin cofactor II is a glycoprotein present in human plasma at a concentration of approximately 1.2 microM. It inhibits thrombin by forming a stable, 11 complex with the protease. The rate of complex formation is increased approximately 1,000-fold by heparin or dermatan sulfate. Heparin cofactor II appears to be the only thrombin inhibitor in plasma that can be activated by dermatan sulfate. Platelet factor 4 abolishes the activation of heparin cofactor II by dermatan sulfate, but plasma histidine-rich glycoprotein does not. Heparin cofactor II is activated by dermatan sulfate oligosaccharides that are at least 12-14 sugar residues in length and contain a high-affinity binding site for the inhibitor protein.