Tissue factor: from 'just one of the coagulation factors' to a major player in physiology

As early as the nineteenth century, it was recognized that tissues exhibit clot-promoting activity. The realization that a single protein was responsible for this procoagulant effect led to the discovery of tissue factor (TF), but for many years it was thought that TF activity was restricted to the activation of an auxiliary pathway that had little biological relevance. Research over recent decades has greatly improved our understanding of TF function, and today the protein is recognized to be the primary biological initiator of the coagulation cascade. Furthermore, it is now clear that TF is a major player in several other physiological processes. We present recent data suggesting that TF is vital not only for effective haemostasis, but also for angiogenesis and tumour metastasis, for embryonic development, and for induction of a pro-inflammatory response. These advances in our knowledge of TF function will improve our understanding of several pathophysiological conditions, and may expand the therapeutic options available for their treatment.