Studies on Factor VIII Complex in Liver Diseases

Factor VIII procoagulant activity (VIII: C), factor VIII related antigen (VIII R: AG) and von Willebrand factor (VIII R: WF) were measured in patients with liver disease (33 cases of cirrhosis, 8 cases of acute hepatitis, 10 cases of chronic hepatitis, 3 cases of fulminant hepatitis and 3 cases of primary liver cancer) and in 30 normal individuals.Level of the three subunits of factor VIII complex were increased in cirrhotic patients as compared to those in normal individuals. In normal individuals there was a high degree of correlation between the three subunits, whilst this correlation was low in cirrhotic patients. In most cases with liver cirrhosis, high levels of VIII R: AG were not followed by a proportional increase in VIII R: WF or VIII: C. Similar results were obtained in the other liver diseases. These data suggest a functionally or qualitatively different factor VIII complex molecule from that found in normal plasma.The two dimensional crossed immunoelectrophoresis (CIE) of the plasmas from patients with liver disease in whom disproportionately important elevation of VIII R: AG was found as compared with VIII R: WF, revealed abnormalities of the shape and migration of the precipitin arcs with more anodal electrophoretic mobility. The elution profile of the cryoprecipitate on Sepharose 4B of the plasma of liver cirrhosis differed from normal in respect that the partially purified factor VIII protein had markedly reduced VIII R: WF. These studies indicate that some patients with liver disease may comprise both quantitative and qualitative defects of factor VIII complex, presenting discrepancy between VIII R: AG and VIII R: WF.Although the reason for the abnormality is not clear it may be related to the abnormal synthesis of factor VIII protein or to the accumulation of partially degraded protein due to normal or abnormal catabolism, or to disorder of joining or activating VIII: C. An alternative possibility is that it could be due to degradation of the protein by plasmin as the authers previously reported.