title: Factor V, tissue factor pathway inhibitor, and east Texas bleeding disorder.
abstract: In a report reading like a fascinating detective story, Vincent and colleagues crack the mysterious case of east Texas bleeding disorder. They show that affected individuals have a mutation in exon 13 of the coagulation F5 gene that causes increased expression of an alternatively spliced transcript, which encodes a previously unrecognized factor V (FV) isoform they call FV-short. This FV isoform lacks a large portion of the B domain of FV, which is normally released upon the proteolytic activation of FV by thrombin and binds tightly to the coagulation regulator tissue factor pathway inhibitor-α (TFPIα). This interaction leads to an approximately 10-fold increase in the level of TFPIα circulating in plasma and a resultant anticoagulant effect that produces a hemorrhagic diathesis.
authors: Division of Hematology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. gbroze@dom.wustl.edu
authors: George J
authors: GJ
authors: Broze
authors: Thomas J
authors: TJ
authors: Girard
mesh_terms: D025861:Blood Coagulation Disorders, Inherited / Q000235:genetics*; D005165:Factor V / Q000235:genetics*; D006474:Hemorrhagic Disorders / Q000235:genetics*; D006801:Humans; D008074:Lipoproteins / Q000097:blood*
chemical_list: D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005165:Factor V
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