Hemoglobinuria, Paroxysmal Nocturnal

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