Role of tissue factor in hemostasis and thrombosis

Abstract

Tissue factor (TF) is a transmembrane glycoprotein that functions as the primary cellular initiator of blood coagulation. Perivascular cells express TF and provide a hemostatic barrier to limit hemorrhage after vessel injury. In addition, TF is expressed in a tissue-specific manner with high levels in vital organs, such as the heart and lung. TF expression in these tissues may provide additional hemostatic protection from mechanical injury to blood vessels. Recent studies have also detected TF in the blood. This circulating TF is present in the form of microparticles (MPs), which are membrane vesicles shed from cells, and possibly platelets. At present, the cell types that contribute to this pool of TF-positive MPs have not been fully defined. Monocytes, endothelial cells and platelets are the most likely sources of this circulating TF. However, TF-positive MPs represent only a minor subset of circulating MPs. Importantly, TF-negative MPs also possess procoagulant activity. In various diseases, such as sepsis and cancer, TF is expressed by vascular cells and this leads to thrombosis. Levels of circulating TF are also elevated in these diseases and may contribute to thrombosis. Recent studies have analyzed the role of TF-positive MPs in thrombus propagation using different in vivo models. Circulating TF was found to contribute to thrombosis in some models but not others. Inhibition of TF activity in patients with TF expression in vascular cells and with elevated levels of circulating TF may decrease thrombosis associated with a variety of diseases.