Overview of QPD and study design (A) Overview of QPD pathogenesis. QPD is associated with a duplication mutation of PLAU that selectively increases PLAU expression with megakaryocyte differentiation, resulting in a platelet-dependent gain-of-function defect in fibrinolysis, with hemostatic consequences. Images show QPD bleeds in 2 participants, after exercise (top) or a minor fall (bottom). (B) Overview of samples, cell types, and experimental assays. TPO, thrombopoietin; MK, megakaryocytes; HP, hematopoietic progenitor. The schematic in panel A was created with BioRender.com.