Tissue factor in coagulation: Which? Where? When?

Tissue factor (TF) is an integral membrane protein, normally separated from the blood by the vascular endothelium, which plays a key role in the initiation of blood coagulation. With a perforating vascular injury, TF becomes exposed to blood and binds plasma factor VIIa. The resulting complex initiates a series of enzymatic reactions leading to clot formation and vascular sealing. In some pathological states, circulating blood cells express TF as a result of exposure to an inflammatory stimulus leading to intravascular clotting, vessel occlusion, and thrombotic pathology. Numerous controversies have arisen related to the influence of structural features of TF, its presentation, and its function. There are contradictory reports about the synthesis and presentation of TF on blood cells and the presence (or absence) of functionally active TF circulating in normal blood either on microparticles or as a soluble protein. In this review we discuss TF structure-function relationships and the role of TF during various phases of the blood coagulation process. We also highlight controversies concerning the expression/presence of TF on various cells and in blood in normal and pathological states.