Tissue Factor Pathway Inhibitor

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Tissue factor pathway inhibitor (TFPI) is a protein that prevents blood coagulation from starting. It does this by inhibiting two procoagulant complexes:

• Tissue factor–factor VIIa (TF–FVIIa):
• Early forms of prothrombinase

TFPI also inhibits the proteolytic activity of Factor Xa. This inhibits both the initiation tenase (TF-FVIIa) and the “prothrombinase” (FXa/FVa).

TFPI is the main inhibitor of blood coagulation. It also controls the severity of many bleeding and clotting disorders.

TFPI is made up of three Kunitz-type structures:

• First Kunitz domain (K1): Binds to the active site of fVIIa
• Second Kunitz domain (K2): Binds to the active site of fXa

TFPI has heparin binding sites that interact with heparin sulfate on the surface of endothelial cells.