Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content + Print Section ++ For further information, see CMDT Part 13-11: Paroxysmal Nocturnal Hemoglobinuria + Key Features Print Section ++ ++ Acquired clonal hematopoietic stem cell disorder causing abnormal sensitivity of RBC membrane to lysis by complement and therefore hemolysis Defect involves increased binding of C3b and increased vulnerability to lysis by complement Suspect diagnosis in confusing cases of hemolytic anemia or pancytopenia + Clinical Findings Print Section ++ ++ Hemoglobinuria (reddish brown urine), particularly in first morning urine Anemia Increased susceptibility to thrombosis, especially of mesenteric and hepatic veins May appear de novo or arise in the setting of aplastic anemia or myelodysplasia with possible progression to acute myeloid leukemia + Diagnosis Print Section ++ ++ Flow cytometry best screening test to demonstrate absence of CD59 and CD55 on RBCs FLAER assay (fluorescein-labeled proaerolysin) by flow cytometry is even more sensitive Anemia of variable severity Reticulocytosis may or may not be present Urine hemosiderin test may indicate episodic intravascular hemolysis Serum lactate dehydrogenase characteristically elevated Iron deficiency common because of chronic iron loss from hemoglobinuria WBC and platelet count may be low Bone marrow morphology variable; may show generalized hypoplasia or erythroid hyperplasia Bone marrow karyotype may be either normal or demonstrate a clonal abnormality + Treatment Print Section ++ ++ Mild disease does not require intervention Allogeneic hematopoietic stem cell transplantation has been used in severe cases and in those occurring in setting of myelodysplasia or previous aplastic anemia Eculizumab Warranted in patients with severe hemolysis (usually requiring red cell transfusions) or thrombosis Reduces hemolysis, transfusion requirements, fatigue, and thrombosis risk Improves quality of life Expensive Increases the risk of Neisseria meningitidis infections; patients receiving the antibody should undergo meningococcal vaccination and take oral penicillin (or equivalent) meningococcal prophylaxis Iron replacement is indicated for treatment of iron deficiency when present, which may improve the anemia while also causing a transient increase in hemolysis Corticosteroids are effective in decreasing hemolysis