Tissue factor pathway inhibitor and the current concept of blood coagulation

Abstract

Tissue factor pathway inhibitor (TFPI) is a multivalent, Kunitz-type plasma proteinase inhibitor that regulates tissue factor-induced coagulation. TFPI directly inhibits activated factor X and, in a factor Xa-dependent manner, produces feedback inhibition of the factor VIIa/tissue factor catalytic complex. The properties of this inhibitor help explain the clinical need for 'extrinsic' and 'intrinsic' coagulation pathways and have led to a reformulation of the coagulation cascade. In the revised hypothesis, factor VIIa/tissue factor is responsible for the initiation of coagulation but, owing to TFPI-mediated feedback inhibition, amplification of the procoagulant response though the actions of factor VIII, IX and XI is required for sustained haemostasis.