Histidine-rich glycoprotein is elevated in mild liver cirrhosis and decreased in moderate and severe liver cirrhosis

Histidine-rich glycoprotein (HRG) reduces by complex formation with plasminogen the amount of 'free' plasminogen in circulation and is therefore considered an inhibitor of fibrinolysis. We studied the levels of both HRG and plasminogen in patients with different degrees of liver cirrhosis to assess the role of HRG in enhanced fibrinolysis in these patients. In mild (Child A) cirrhosis, HRG levels unexpectedly were significantly increased. The total plasminogen level and the calculated amount of free plasminogen were decreased. In moderate (Child B) cirrhosis, both HRG levels and total plasminogen levels were reduced, resulting in a normal amount of free plasminogen in circulation. In severe (Child C) cirrhosis, HRG level, total plasminogen level, and free plasminogen level were all decreased. Because the HRG level is increased in Child A liver cirrhosis, we suggest that other mechanisms, other than simply a decreased synthetic capacity of the liver, contribute to the changes in HRG levels in patients with liver disease. Because of the reduction of free plasminogen levels in severe liver cirrhosis, we propose that the decrease in HRG levels in liver cirrhosis plays no role in enhanced fibrinolysis in these patients. The increase in the HRG level in Child A liver cirrhosis may be of importance in future studies on familial thrombosis associated with elevated levels of HRG, where mild liver dysfunction should at least be excluded.