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Tissue factor pathway inhibitor (TFPI) is the major physiological regulator of tissue factor (TF)-induced blood coagulation. TFPI inhibits the TF-activated factor VII (FVIIa) complex in an activated factor X (FXa)-dependent manner, helping to control thrombin generation and ultimately fibrin formation. The importance of TFPI is demonstrated in models of hemophilia where lower levels of FVIII or FIX are insufficient to overcome its inhibitory effect, resulting in a bleeding phenotype. There are two major isoforms in vivo; TFPIα contains three Kunitz-type inhibitory domains (designated K1, K2, and K3), is secreted by endothelial cells and requires protein S to enhance its anticoagulant activity. In contrast, TFPIβ contains only the K1 and K2 domains, but it is attached to the endothelial surface via a glycosylphosphatidylinositol anchor. This review will initially provide a brief history of the major discoveries related to TFPI, and then discuss new insights into the physiology of TFPI, including updates on its association with protein S and FV, as well as the current understanding of its association with disease.

Item Type:	Substantial Review
Keywords:	TFPI, Haemostasis, Thrombosis, Haemophilia
Research Division:	Medical and Health Sciences
Research Group:	Cardiorespiratory Medicine and Haematology
Research Field:	Haematology
Objective Division:	Health
Objective Group:	Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:	Blood Disorders
UTAS Author:	Adams, MJ (Dr Murray Adams)
ID Code:	97009
Year Published:	2014
Web of Science® Times Cited:	12
Deposited By:	Health Sciences A
Deposited On:	2014-11-28
Last Modified:	2015-05-12
Downloads:	0