Inhibition of Factor VIIa tissue factor activity requires a plasma component (tissue factor pathway inhibitor (TFPI), lipoprotein-associated coagulation inhibitor (LACI) or extrinsic pathway inhibitor (EPI)) and factor Xa. TFPI directly inhibits factor Xa, and, in an Xa-dependent fashion, also inhibits the Factor VIIa tissue factor catalytic complex. TFPI is a multivalent, Kunitz-type proteinase inhibitor that circulates in association with plasma lipoproteins VLDL, LDL, and HDL. TFPI-2 (also known as placental protein 5) is a related glycoprotein that was originally isolated from human placenta.