TISSUE FACTOR PATHWAY INHIBITOR (TFPI) - AN UPDATE

There is compelling experimental evidence that tissue factor pathway i nhibitor (TFPI) exerts important role(s) as a natural anticoagulant. I mmunodepletion of TFPI lowers the treshold by which tissue factor (TF) can induce disseminated intravascular coagulation. Conversely, infusi on of recombinant TFPI protects against thrombosis and disseminated in travascular coagulation in numerous experimental models. Since TFPI mu tants associated with thrombosis have not yet been identified, a defin ite role of TFPI in coagulation is yet to be assigned. Current researc h on TFPI is mainly focused on the cell biology of TFPI, on the contri bution of TFPI to the anticoagulant action of heparins, and on the rol e of lipoprotein-associated TFPI. TFPI is produced constitutively in e ndothelial cells, and is to a great extent bound to its surface. The b inding molecule(s) have not yet been characterized, but TFPI is rapidl y released by heparin and other negatively charged ions. In other cell lines degradation of TFPI is mediated by the low density lipoprotein receptor-related protein, which may be important for its clearance. In plasma, TFPI contributes strongly to the postheparin anticoagulant ef fect seen in dilute prothrombin time assays. The effect is probably me diated by redistribution of TFPI. Moreover, in the presence of heparin , antithrombin and TFPI cooperate to inhibit activation of coagulation . Antithrombin abrogates activation of factor VII bound to TF, whereas TFPI inhibits factor VIIa/TF complexes formed. The role of lipoprotei n associated TFPI is still essentially unknown, but may play an import ant role in atherosclerosis.