A unique gain-of-function defect in fibrinolysis causes the Quebec platelet disorder (QPD) which is characterized by profibrinolytic platelets containing increased urokinase-type plasminogen activator (uPA) in the α-granules.
QPDPLAU transcripts were consistent with reference gene models, with a much higher proportion of reads originating from the disease chromosome in megakaryocytes than granulocytes.
QPD is the first bleeding disorder identified to be caused by a PLAU mutation and it is also the first bleeding disorder recognized to result from a gene copy number mutation.
Although QPD CD34(+) progenitors expressed normal amounts of uPA, their differentiation into megakaryocytes abnormally increased expression of the uPA gene but not the flanking genes for vinculin or calcium/calmodulin-dependent protein kinase IIgamma on chromosome 10.
Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder associated with increased urokinase-type plasminogen activator in platelets and alpha-granule protein degradation.
Although patients with the QPD have normal to increased u-PA levels in their plasma, without evidence of systemic fibrinogenolysis, their increased platelet u-PA could contribute to bleeding by accelerating fibrinolysis within the hemostatic plug.