The effect of liver disease on factors V, VIII and protein C.
The components of the factor VIII complex were estimated by immuno- and bioassays in 85 patients with liver disease. The plasma concentrations of the antigens were elevated in 65% (VIII:CAg) and in 76% (VIIIR:Ag) of patients while the biological activities were elevated in only 14% (VIII:C) and 15% (VIII:RiCof). There was no correlation with C-reactive protein, used as a measure of an acute phase reaction (X2 = 0.7; P = 0.1); or with severity of liver disease as judged by prothrombin ratio (P = 1.0) but highest values were observed in patients with cholestatic liver disease. Following parenteral vitamin K there was a significant fall in both the biological activity of VIIIC (36%) and of VIII:CAg (38%) in 13 vitamin K deficient patients (P less than 0.001) but no change in 23 vitamin K replete patients or in the VIIIR:Ag levels in either group. Factor V levels were lower in patients with parenchymal liver disease (0.54 +/- 0.1 units/ml, mean +/- SEM, n = 12; normal range 0.5-1.5 units/ml) than in patients with extrahepatic cholestasis who were vitamin K deficient (1.2 +/- 0.1 units/ml, P less than 0.0001). The levels of protein C antigen, the vitamin K dependent protease which inactivates factors VIII:C and V, was at the lower end of the range in both groups (0.7 +/- 0.1, mean +/- SEM, n = 18, normal range 0.74-1.4 units/ml). There was no significant change in either protein C antigen or factor V following vitamin K. The discrepancy between the biological activity of factor VIII and the antigen levels could represent accumulation of partially degraded factor VIII or production of a hypoactive form. There is no evidence that the reduction in VIIIC and VIII:CAg following vitamin K was mediated by protein C.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000941:Antigens / Q000032:analysis; D005165:Factor V / Q000032:analysis*; D005169:Factor VIII / Q000032:analysis* / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D008107:Liver Diseases / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D011486:Protein C; D012310:Ristocetin / Q000494:pharmacology; D014812:Vitamin K / Q000494:pharmacology; D014813:Vitamin K Deficiency / Q000097:blood; D014841:von Willebrand Factor
D000941:Antigens; D006023:Glycoproteins; D011486:Protein C; D014841:von Willebrand Factor; D014812:Vitamin K; D012310:Ristocetin; D005165:Factor V; D005169:Factor VIII