Vitamin E reduces monocyte tissue factor expression in cirrhotic patients

Clotting activation may occur in liver cirrhosis, but the pathophysiological mechanism has not been fully elucidated. Because a previous study demonstrated that lipid peroxidation is increased in cirrhosis, we analyzed whether there is a relationship between lipid peroxidation and clotting activation. Thirty cirrhotic patients (19 men and 11 women; age, 34 to 79 years) and 30 controls matched for sex and age were investigated. In all subjects, monocyte expression of tissue factor (TF) antigen and activity; plasma levels of prothrombin fragment 1 + 2 (F1 + 2), a marker of thrombin generation; and urinary excretion of Isoprostane-F-2 alpha-III, a marker of lipid peroxidation, were measured. Furthermore, the above-reported variables were re-evaluated after 30 days of treatment with standard therapy (n = 5) or standard therapy plus 300 mg vitamin E twice daily (n = 9). In addition, we analyzed in vitro if vitamin E (50 mu mol/L) influenced monocyte TF expression and F1 + 2 generation. Cirrhotic patients had higher values of isoprostane-F2 alpha-III (P < .0001), F1 + 2 (P < .0001), and monocyte TF antigen (P < .0001) and activity (P <.03) than controls. Isoprostane-F-2 alpha-III was significantly correlated with F1 + 2 (Rho = 0.85; P < .0001) and TF antigen (Rho = 0.95; P < .0001) and activity (Rho = 0.94; P < .0001). After vitamin E treatment, Isoprostane-F2 alphaIII (P = .008), F1 + 2 (P < .008), and monocyte TF antigen (P = .012) and activity (P = .008) significantly decreased; no changes of these variables were detected in patients not receiving vitamin E. In vitro, vitamin E significantly reduced the expression of monocyte TF antigen (-52%; P = .001) and activity (-55%; P = .003), as well as F1 + 2 generation (-51%; P = .025), This study shows that vitamin E reduces both lipid peroxidation and clotting activation and suggests that lipid peroxidation may be an important mediator of clotting activation in liver cirrhosis. (C) 1999 by The American Society of Hematology.