title: Quebec platelet disorder: update on pathogenesis, diagnosis, and treatment.
abstract: Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder associated with reduced platelet counts and a unique gain-of-function defect in fibrinolysis due to increased expression and storage of urokinase plasminogen activator (uPA) by megakaryocytes. QPD increases risks for bleeding and its key clinical feature is delayed-onset bleeding, following surgery, dental procedures or trauma, which responds only to treatment with fibrinolytic inhibitors. The genetic cause of the disorder is a tandem duplication mutation of the uPA gene,  PLAU, which upregulates uPA expression in megakaryocytes by an unknown mechanism. The increased platelet stores of uPA trigger plasmin-mediated degradation of QPD α-granule proteins. The gain-of-function defect in fibrinolysis is thought to be central to the pathogenesis of QPD bleeding as the activation of QPD platelets leads to release of uPA from α-granules and accelerated clot lysis. The purpose of this review is to summarize current knowledge on QPD pathogenesis and the recommended approaches to QPD diagnosis and treatment.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Blavignac
authors.forename: Natalia
authors.initials: N
authors.lastname: Bunimov
authors.forename: Georges E
authors.initials: GE
authors.lastname: Rivard
authors.forename: Catherine P M
authors.initials: CP
authors.lastname: Hayward
mesh_terms: D000933:Antifibrinolytic Agents / Q000627:therapeutic use; D005166:Factor V Deficiency / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006470:Hemorrhage / Q000188:drug therapy; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology; D014148:Tranexamic Acid / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid; D014568:Urokinase-Type Plasminogen Activator