title: Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein.
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.
authors.affiliation: From the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee; and Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee. alan.mast@bcw.edu.
authors.forename: Alan E
authors.initials: AE
authors.lastname: Mast
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects / Q000235:genetics; D025861:Blood Coagulation Disorders, Inherited / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D003029:Coagulants / Q000627:therapeutic use; D015942:Factor VIIa / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D020033:Protein Isoforms; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D003029:Coagulants; D008074:Lipoproteins; D020033:Protein Isoforms; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D015942:Factor VIIa
keywords: factor V; factor VII; hemophilia A; lipoprotein-associated coagulation inhibitor; thromboplastin