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Factor V, tissue factor pathway inhibitor, and east Texas bleeding disorder
George J. Broze Jr., Thomas J. Girard
George J. Broze Jr., Thomas J. Girard
Published August 27, 2013
Citation Information: J Clin Invest. 2013;123(9):3710-3712. https://doi.org/10.1172/JCI71220.
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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

George J. Broze Jr., Thomas J. Girard

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