The effect of liver disease on factors V, VIII and protein C

S ummary . 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 activites 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 (χ 2 =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 <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 <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.