Paroxysmal nocturnal hemoglobinuria

Introduction

PNH = Intravascular hemolysis caused by increased sensitivity of RBCs to hemolytic action of complement


Pathophysiology

  • Abnormal PIG-A gene > defect in GPI-linked anchor > partial/complete absence of GPI-linked proteins (mainly CD55 and CD59) > increased sensitivity of RBCs to hemolytic action of complement


  • Hemolysis precipitated by stresses that activate complement (eg infection)
    • Nocturnal hemolysis attributed to intestinal absorption of lipopolysaccharide (strong activator of complement) at night


Diagnosis

  • Anemia
  • Negative Coombs test
  • Hemoglobinuria
  • Elevated LDH
  • Decreased haptoglobin
  • Positive sucrose lysis test or Ham test (both test sensitivity of RBCs to lysis by complement)
  • Other clues: granulocytopenia/thrombocytopenia, venous thrombosis, aplastic anemia, MDS, dysphagia or abdominal pain


Clinical Manifestations

  • Intravascular hemolysis
  • Renal failure (both from intravascular hemolysis causing AKI and chronic hemolysis causing iron deposition in kidneys)
  • DVT, thrombosis of hepatic/intraabdominal/cerebral veins, arterial thrombosis
  • Bone marrow failure leading to aplastic anemia
  • Myelodysplastic (MDS) or myeloproliferative disorders
  • Acute leukemia
  • Esophageal spasm
  • Crampy abdominal pain
  • Impotence/ED


Treatment

  • Eculizumab (C5 antibody): stops hemolysis in PNH
  • Iron/folate supplements
  • RBC transfusion PRN
  • Prednisone may decrease RBC destruction
  • For severe hematopoietic dysfunction w/ marked cytopenias: hematopoietic cell transplant or immunosuppression (cyclosporine or antithymocyte globulin)
  • Anticoagulation for thrombosis


See Also