Activation of heparin cofactor II by dermatan sulfate

We have tested the ability of various glycosaminoglycans to increase the rate of inhibition of thrombin by heparin cofactor II (HCII) and by antithrombin III (ATIII) isolated from human plasma. Heparin, dermatan sulfate, and heparan sulfate from bovine liver (in order of decreasing activity) activated HCII. In contrast, only heparin and bovine liver heparan sulfate activated ATIII, whereas dermatan sulfate was inactive at concentrations ≤ 1 mg/ml. Heparan sulfate from human aorta, chondroitin 4-sulfate, chondroitin 6-sulfate, keratan sulfate, and hyaluronic acid had little or no activity with either HCII or ATIII. The second order rate constant for the thrombin-HCII reaction reached a maximum value of 6.4 x 10⁸ M^-1 min^-1 in the presence of 250-500 μg/ml of dermatan sulfate compared to 3.8 x 10⁸ M^-1 min^-1 in the presence of 40-80 μg/ml of heparin. When ¹²⁵I-thrombin was incubated with plasma in the presence of ≥100 μg/ml of dermatan sulfate, the protease became complexed exclusively with HCII, suggesting that HCII is the only thrombin inhibitor in human plasma that can be activated by dermatan sulfate.