TISSUE FACTOR PATHWAY INHIBITOR AND THE REVISED HYPOTHESIS OF BLOOD-COAGULATION

The recent rediscovery, isolation, and characterization of an endogenous coagulation inhibitor termed tissue factor pathway inhibitor (TFPI) has provided new insight into the regulation of in vivo coagulation. TFPI is a multivalent, Kunitz-type, protease inhibitor that directly binds and inactivates factor Xa and, in a factor-Xa-dependent fashion, produces feedback inhibition of the factor VIIa-tissue factor catalytic complex. The demonstrated in vitro properties of TFPI have led to the formulation of a revised theory of blood coagulation. In the revised model, coagulation proceeds through a single pathway rather than the alternative and redundant "extrinsic" and "intrinsic" pathways that had previously been postulated.