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For further information, see CMDT Part 13-11: Paroxysmal Nocturnal Hemoglobinuria

Key Features

  • 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

  • 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

  • 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

  • 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

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