Pentoxifylline: a potential treatment for thrombosis associated with abnormal tissue factor expression by monocytes and endothelial cells.

Tissue factor (TF) is a transmembrane glycoprotein that acts as the cell receptor for factor VII and activated factor VII (VIIa) and as the co-factor for VIIa. Because binding of factor VII/VIIa to its receptor is the first step in the activation of the coagulation process, TF is not normally expressed by circulating cells. Monocytes and endothelial cells are, however, capable of producing TF in response to diverse stimuli. TF expression is believed to be responsible for thrombotic complications associated with certain diseases. In vitro, pentoxifylline (PTX) inhibits monocyte production of TF in response to endotoxin, as well as endothelial cell production of TF in response to tumor necrosis factor-alpha (TNF-alpha). In vivo, injection of PTX into primates prevents the activation of coagulation by endotoxin. The potential benefit of this treatment in patients with septic shock and disseminated intravascular coagulation, as well as in other clinical conditions in which TF expression is increased, remains to be determined in well-designed clinical trials.