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Tissue Factor Pathway Inhibitor: Then and Now
journal contribution
posted on 2023-05-22, 23:43 authored by Ellery, PER, Adams, MJTissue 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.
History
Publication title
Seminars in Thrombosis and HemostasisVolume
40Issue
8Pagination
881-886ISSN
0094-6176Department/School
School of Health SciencesPublisher
Thieme Medical Publ IncPlace of publication
333 Seventh Ave, New York, USA, Ny, 10001Repository Status
- Restricted