Histidine-rich glycoprotein modulates the anticoagulant activity of heparin in human plasma.

Addition of 0.05 IU of heparin per ml normal plasma prolongs its thrombin time from 20 to 27s , but that of plasma specifically depleted in histidine-rich glycoprotein (by immunoadsorption) from 20 to 180s . Reconstitution of the depleted plasma with normal plasma or with purified histidine-rich glycoprotein normalizes its thrombin time. In 54 plasma samples from hospitalized patients a significant negative correlation was found between the anticoagulant activity of heparin measured by thrombin inhibition and the plasma level of histidine-rich glycoprotein (r = 0.69). It is concluded that the level of histidine-rich glycoprotein modulates the anticoagulant activity of heparin in human plasma to an extent which appears to be pharmacologically and possibly clinically relevant.