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 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.
Broze
G J
GJ
Division of Hematology, Washington University School of Medicine, Jewish Hospital, St. Louis, Missouri 63110, USA.
D000595:Amino Acid Sequence / Q000235:genetics; D001777:Blood Coagulation / Q000235:genetics / Q000502:physiology*; D015942:Factor VIIa / Q000502:physiology; D005170:Factor X / Q000037:antagonists & inhibitors / Q000502:physiology; D005246:Feedback / Q000502:physiology; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D008074:Lipoproteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D013925:Thromboplastin / Q000502:physiology
D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005170:Factor X; D013925:Thromboplastin; D015942:Factor VIIa