Tissue factor pathway inhibitor is a potent inhibitor of plasmin

Recombinant tissue factor pathway inhibitor (TFPI) was found to be a potent inhibitor of plasmin. In an amidolytic assay the inhibition constant K-i was found to be 2.86 x 10(-8) M. TFPI in the same concentration range also inhibited the activation of plasminogen by tissue plasminogen activator (tPA). The amidolytic activity of tPA was not inhibited by TFPI. Other proteinases relevant to fibrinolysis such as urokinase, alpha-factor XIIa, and beta-factor XIIa were not inhibited by TFPI. Plasma kallikrein was weakly inhibited by TFPI. When added to plasma, TFPI also prolonged the euglobulin lysis time. The interaction of TFPI with heparin and a mucopolysaccharide polysulfuric ester, a heparin-like glycosaminoglycan, was studied. Heparin augmented plasmin inhibition by TFPI, while mucopolysaccharide polysulfuric ester had no effect.