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

• DIC, TTP, HUS, Microangiopathic Hemolytic Anemia (MAHA)
• HELLP, HIT, Hereditary Sperocytosis (HS)