Tissue factor pathway inhibitor in thrombosis and beyond: role of heparin

Tissue factor (TF) plays a crucial role in the pathogenesis of thrombosis, angiogenesis and inflammatory disorders, and the inhibition of this membrane protein thus provides a unique therapeutic approach for the prophylaxis and/or treatment of various diseases. In the past few years, TF pathway inhibitor (TFPI), the only endogenous inhibitor of the TF/FVIIa complex, has been characterized biochemically and pharmacologically. Studies in patients have demonstrated that both TF and TFPI may be indicators for the course and the outcome of cardiovascular and other diseases. Based on experimental and clinical data, TFPI may become an important drug or target for several clinical indications. Tissue factor pathway inhibitor is expected to inhibit the development of postinjury intimal hyperplasia and thrombotic occlusion in atherosclerotic vessels, as well as to be effective in acute coronary syndromes such as unstable angina and myocardial infarction. Of special interest is the inhibition of TF-mediated processes in sepsis and disseminated intravascular coagulation. At present, clinical studies with TFPI are rather limited, so the clinical potential of the drug cannot be properly assessed. However, TFPI and its variants are expected to undergo further development and to find indications in various clinical states.