Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein.
Review published in Arteriosclerosis, thrombosis, and vascular biology (2015)
Abstract
Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits early phases of the procoagulant response. Alternatively spliced isoforms of TFPI are differentially expressed by endothelial cells and human platelets and plasma. The TFPIβ isoform localizes to the endothelium surface where it is a potent inhibitor of TF-factor VIIa complexes that initiate blood coagulation. The TFPIα isoform is present in platelets. TFPIα contains a stretch of 9 amino acids nearly identical to those found in the B-domain of factor V that are well conserved in mammals. These amino acids provide exosite binding to activated factor V, which allows for TFPIα to inhibit prothrombinase during the initiation phase of blood coagulation. Endogenous inhibition at this point in the coagulation cascade was only recently recognized and has provided a biochemical rationale to explain the pathophysiological mechanisms underlying several clinical disorders. These include the east Texas bleeding disorder that is caused by production of an altered form of factor V with high affinity for TFPI and a paradoxical procoagulant effect of heparins. In addition, these findings have led to ideas for pharmacological targeting of TFPI that may reduce bleeding in hemophilia patients.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits early phases of the procoagulant response. Alternatively spliced isoforms of TFPI are differentially expressed by endothelial cells and human platelets and plasma.
Por qué esto importa para la hirudoterapia
This review examines tissue factor pathway inhibitor (TFPI), an anticoagulant protein with alternatively spliced isoforms differentially expressed by endothelial cells and platelets. The TFPIα isoform contains amino acids nearly identical to the factor V B-domain, enabling exosite binding to activated factor V and inhibition of prothrombinase during coagulation initiation. These insights explain clinical disorders such as east Texas bleeding disorder and a paradoxical procoagulant effect of heparins, and suggest pharmacological TFPI targeting for hemophilia. For ASH's domain, the article contributes to understanding endogenous anticoagulant mechanisms relevant to the broader field of anticoagulation science. However, there is no mention of leeches, hirudotherapy, or the leech secretome, and the connection to ASH's domain is limited to general coagulation biology.
Citación
Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein.
Mast · Arteriosclerosis, thrombosis, and vascular biology, 2015
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Añadido a la biblioteca ASH: May 28, 2026 · Última actualización del sitio: June 18, 2026