Blood, Vol. 93 No. 9 (May 1), 1999:
pp. 2945-2950
Vitamin E Reduces Monocyte Tissue Factor Expression in Cirrhotic
Patients
Domenico Ferro,
Stefania Basili,
Domenico Praticó,
Luigi Iuliano,
Garret A. FitzGerald, and
Francesco Violi
From the Department of Internal Medicine, I Clinica Medica, and
Department of Therapeutic Medicine, University "La Sapienza,"
Rome, Italy; and the Center for Experimental Therapeutics, University
of Pennsylvania, Philadelphia, PA.
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-F2
-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 µmol/L) influenced monocyte TF expression and F1+2 generation. Cirrhotic patients had higher values of Isoprostane-F2-III
(P < .0001), F1+2 (P < .0001), and monocyte TF
antigen (P < .0001) and activity (P < .03) than
controls. Isoprostane-F2-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-III (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.
