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Description
TFPI is a serine protease inhibitor that regulates the tissue factor (TF)-dependent pathway of blood coagulation. The coagulation process initiates with the formation of a factor VIIa-TF complex, which proteolytically activates additional proteases (factors IX and X) and ultimately leads to the formation of a fibrin clot. TFPI is known to interact and inhibit the activated factor X and VIIa-TF proteases in an autoregulatory loop. TFPI is a dual inhibitor, binding to the TF/FVIIa complex to prevent it from acting on its FIX and FX substrates, and by directly inhibiting FXa. Inadequate down-regulation of FXa function by TFPI deficiency leads to thrombosis. Besides coagulation, TFPI may play additional roles in innate immunity, microbial defense, inflammation, angiogenesis, lipid metabolism, and cellular signaling, proliferation, migration, and apoptosis.