TISSUE FACTOR PATHWAY INHIBITOR AND THE REVISED THEORY OF COAGULATION

Tissue factor pathway inhibitor (TFPI) is a multivalent, Kunitz-type plasma proteinase inhibitor that regulates tissue factor-induced coagulation. TFPI directly inhibits activated factor X and, in a factor Xa-dependent fashion, produces feedback inhibition of the factor VIIa/tissue factor catalytic...

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Bibliographic Details
Published in:Annual review of medicine 1995-01, Vol.46 (1), p.103-112
Main Author: Broze, George J
Format: Article
Language:English
Subjects:
Amino Acid Sequence - genetics
Biological and medical sciences
Blood Coagulation - genetics
Blood Coagulation - physiology
Blood coagulation. Blood cells
cascade
Factor VIIa - physiology
Factor X - antagonists & inhibitors
Factor X - physiology
Feedback - physiology
Fundamental and applied biological sciences. Psychology
General aspects, investigation methods, hemostasis, fibrinolysis
Hemostasis - physiology
Humans
Kunitz
Lipoproteins - genetics
Lipoproteins - physiology
Molecular and cellular biology
Molecular Sequence Data
proteinase
Thromboplastin - physiology
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Summary:Tissue factor pathway inhibitor (TFPI) is a multivalent, Kunitz-type plasma proteinase inhibitor that regulates tissue factor-induced coagulation. TFPI directly inhibits activated factor X and, in a factor Xa-dependent fashion, produces feedback inhibition of the factor VIIa/tissue factor catalytic complex. The properties of this rediscovered inhibitor appear, at least in part, to explain the clinical requirement for both the extrinsic and intrinsic pathways of the cascade and waterfall theories of blood clotting and have led to a reformulation of the coagulation mechanism. In the revised hypothesis, factor VIIa/tissue factor is responsible for the initiation of coagulation, but owing to TFPI-mediated inhibition, sustained hemostasis requires the persistent and amplified procoagulant action of intrinsic factors VIII, IX, and XI.
ISSN:0066-4219
1545-326X
DOI:10.1146/annurev.med.46.1.103