Congenital deficiency of histidine-rich glycoprotein: failure to identify abnormalities in routine laboratory assays of hemostatic function, immunologic function, and trace elements.

Histidine-rich glycoprotein (HRGP) has many biologic activities, but its physiologic function is still unclear. To show the physiologic function of HRGP, we studied five patients with congenital HRGP deficiency. Hemostatic screening tests, activities of natural anticoagulants and fibrinolytic proteins, markers of thrombin and plasmin generation, plasma levels of platelet-specific proteins, thrombin times with various concentrations of bovine thrombin, prolongation of thrombin time after addition of heparin or demartan sulfate, and contact activation of blood coagulation were normal or nearly normal in these patients. Serum concentrations of immunoglobulin, functional activity of the classical and the alternative pathway of complement, lymphocyte subsets, and serum concentrations of soluble interleukin-2 receptor were approximately normal in all patients, and serum concentrations of copper and zinc were completely normal. These results suggest that the physiologic functions of HRGP are limited when compared with its biologic activities. However, because the patients examined had plasma HRGP levels of 20% to 35% of normal, it is possible that 20% of normal HRGP level is sufficient for its physiologic functions.