The effect of sodium warfarin on rabbit monocyte tissue factor expression.

A rabbit model was developed to examine the effect of sodium warfarin on peripheral blood monocyte tissue factor (MTF) activity. After three days of treatment with sodium warfarin, MTF expression was significantly impaired (p less than 0.003). Vitamin K reversed this inhibition despite continued treatment with warfarin. Animals resistant to warfarin did not become anticoagulated and failed to demonstrate inhibition of MTF expression. Cells grown in plasma from warfarin-treated animals expressed reduced amounts of MTF activity, while cells grown in normal rabbit plasma demonstrated procoagulant activity in assays using both normal and factor VII-deficient substrate plasmas. These studies suggest that normal factor VII binds to monocytes during the culture period. Moreover, a plasma component in warfarin-treated animals, possibly abnormal factor VII, may bind to monocytes and block expression of MTF activity. This may represent another mechanism for warfarin-mediated inhibition of cell-mediated coagulation reactions in vivo.