The role of the tissue factor pathway in haemostasis and beyond

The role of tissue factor (TF) in the initiation of the blood coagulation network leading to generation of a fibrin clot has been well defined over the past 50 years. Although much is known about this sequence of events and its regulation, many important questions remain unresolved. More recently, a complex role for TF in cellular processes independent of fibrin generation has emerged. This review summarizes some of the advances in this field.

TF is the cellular receptor and cofactor for factor VII/VIIa; however, controversy still surrounds expression of TF within the vasculature, the role of circulating microvesicle pools of TF and mechanisms of 'encryption' of TF activity. However, there have been significant advances in the role of TF-initiated cell signalling. Lastly, an alternatively spliced TF transcript has been identified and some insights into its role in cancer cell metastasis/proliferation have been elucidated.

Understanding of TF structure function has increased substantially; however, multiple controversies still surround some aspects of its regulation. TF has emerged as a pivotal player in orchestrating not only fibrin generation but wound repair. Derangement of these repair processes contributes significantly to the pathophysiology of a number of disease processes.