PENTOXIFYLLINE - A POTENTIAL TREATMENT FOR THROMBOSIS ASSOCIATED WITHABNORMAL TISSUE FACTOR EXPRESSION BY MONOCYTES AND ENDOTHELIAL-CELLS

Tissue factor (TF) is a transmembrane glycoprotein that acts as the ce ll 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 endothelia l cells are, however, capable of producing TF in response to diverse s timuli. TF expression is believed to be responsible for thrombotic com plications 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 necrosi s factor-alpha. (TNF-alpha). In vivo, injection of PTX into primates p revents the activation of coagulation by endotoxin. The potential bene fit of this treatment in patients with septic shock and disseminated i ntravascular coagulation, as well as in other clinical conditions in w hich TF expression is increased, remains to be determined in well-desi gned clinical trials.