Tissue factor pathway inhibitor (TFPI), also known as extrinsic pathway inhibitor (EPI), lipoprotein-associated coagulation inhibitor (LACI), is a plasma proteinase inhibitor which controls the tissue factor (TF)-dependent pathway of blood coagulation. ?The major site of TFPI production is in endothelial cells, which constitutively express the protein under normal conditions. TFPI is also normally expressed by vascular smooth muscle cells, megakaryocytes/platelets, monocytes, mesangial cells fibroblasts, and cardiomyocytes. In addition, TFPI has been detected in macrophages and T cells in atherosclerotic lesions. TFPI contains three tandem Kunitz-type serine protease inhibitor domains, K1, K2, and K3, followed by a basic C-terminal region. K2 directly binds to and inhibits the active site of FXa K1 binds to and inhibits the active site of FVIIa, thereby inhibiting procoagulant activity produced by the TF–FVIIa catalytic complex. An alternatively transcribed isoform with GPI anchor arises through differential splicing of the TFPI mRNA toward the 5’-end of the coding region. This membrane anchored protein, referred to as TFPI-β, is a smaller size protein without K3 and basic c-terminal domain. Upregulators of TFPI expression in vitro that might be of physiological significance include endotoxin, interleukin-1, tumor necrosis factor-α, platelet-derived growth factor, heparin, basic fibroblast growth factor, and elevated shear stress. TFPI is distributed in three ways in vivo; about 80 to 85% of the total body TFPI is bound to endothelial cell-surface, and 15-20% is circulating in plasma, of which 80% is bound to lipoproteins and the rest is the free form.