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DOI: 10.1055/s-0031-1291382
Quebec Platelet Disorder: Update on Pathogenesis, Diagnosis, and Treatment
Publication History
Publication Date:
18 November 2011 (online)

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.
KEYWORDS
Quebec platelet disorder - urokinase plasminogen activator - platelets - congenital platelet disorders - fibrinolysis - congenital thrombocytopenia
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Catherine P.M. HaywardM.D. Ph.D. F.R.C.P. (C)
Department of Pathology and Molecular Medicine, McMaster University
2N29A, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada
Email: haywrdc@mcmaster.ca