Quebec Platelet Disorder Is Associated With Greater Than Expected Increases In Urokinase Plasminogen Activator In Granulocytes and Monocytes

Myeloid leukocytes produce urokinase plasminogen activator (uPA), an important activator of fibrinolysis. Stimuli such as lipopolysaccharide and formyl-methionyl-leucyl-phenylalanine (LPS/fMLP), increase the expression of PLAU by myeloid leukocytes. We postulated that the basal, and/or stimulus-induced, uPA production by myeloid leukocytes would be increased in Quebec platelet disorder (QPD), a congenital bleeding disorder caused by duplication of PLAU, the uPA gene. In QPD, plasma and urine uPA levels are within the expected range. However, overexpression of PLAU in QPD was found to emerge during megakaryopoiesis and QPD platelets to contain >100-fold increased uPA.