Identification of heparin cofactor II as the principal plasma cofactor for the antithrombin activity of pentosan...

In antithrombin III depleted plasma only a slight reduction was observed in thrombin inhibitory activity due to potentiation by dermatan sulphate or by pentosan polysulphate (SP54). On gel filtration of normal plasma the peak of pentosan polysulphate dependent activity eluted with a higher apparent molecular weight than that observed with low concentrations of heparin. During purification of heparin cofactor II (1) good coincidence was observed between yields of its activity and the pentosan polysulphate dependent inhibitory activity and cochromatography of the two activities was observed also. Maximal second order rate constant of 2.5 X 10(8) M-1 min-1 (with apparent Kd of 1.8 microM) was found for the potentiation of the thrombin/heparin cofactor II interaction by pentosan polysulphate. A polysaccharide of high charge density may therefore potentiate heparin cofactor II activity and this may be of importance in vivo.