Snapshot A 29-year-old woman presents to the emergency room with a high fever and cough. She has been feeling fatigued for a year prior to presentation. Chest radiography reveals a lower lobe pneumonia. Labs reveal Hb 6.7 g/dL, leukocyte count of 5,000/mm3, platelets of 100,000/mm3,high reticulocyte count, and high LDH. Coombs test was negative. Concerned with the apparent intravascular hemolysis, a bone marrow biopsy showed hypercellularity and normal cytogenetics. Flow cytometry was positive for CD55/CD59-negative RBCs. Introduction Clonal stem cell defect from mutation in hematopoietic stem cell May cause login to view 3 more bullets ETIOLOGY Pathogenesis login to view 6 more bullets "PNH Thrombosis" login to view 5 more bullets Presentation Symptoms/physical exam login to view 15 more bullets STUDIES Flow cytometry – most accurate test login to view 1 more bullet Labs login to view 3 more bullets Differential Diagnosis Aplastic anemia Myelodysplasia DIAGNOSIS Diagnosis often made during pregnancy Treatment Best initial therapy – eculizumab (or ravulizumab) login to view 4 more bullets Best curative therapy – allogeneic bone marrow transplant Supportive therapy login to view 2 more bullets Complications Renal insufficiency Thromboembolism 5% develop myelodysplasia 2.5% develop acute leukemias Prognosis Improved with use of eculizumab