Characterization of an autosomal dominant bleeding disorder caused by a thrombomodulin mutation.

ABSTRACT: We describe a family with an autosomal dominant disorder characterized by severe trauma- and surgery-related bleeding. The proband, who experienced life-threatening bleeding during a routine operation, had normal clotting times, but markedly reduced prothrombin consumption. Plasma levels of all coagulation factors and of the main coagulation inhibitors were normal. Thrombin generation at low triggers was severely impaired and mixing experiments suggested the presence of a coagulation inhibitor. Using whole exome sequencing, the underlying genetic defect was identified as the THBD c.1611C>A mutation (p.Cys537Stop), which predicts a truncated form of thrombomodulin that is shed from the vascular endothelium. The patient had decreased expression of endothelium-bound thrombomodulin, but extrem

SUBMITTER: Dargaud Y 

PROVIDER: S-EPMC4342361 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature