Paroxysmal Nocturnal Hemoglobinuria - PNH

Paroxysmal Nocturnal Hemoglobinuria - PNH

 

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hemolytic disorder caused by a stem cell mutation which results in deficient cell surface glycol phosphatidylinositol anchoring proteins, including complement pathway regulatory proteins

Epidemiology

  • Incidence – 1-4/1,000,000
  • Sex – equal gender distribution
  • Age of onset – teens to 20s

Classification

  • Classic PNH
  • PNH associated with marrow abnormality
  • Subclinical PNH

Pathophysiology

  • Consequence of nonmalignant clonal expansion of one or more stem cells that have acquired a mutation of glycol phosphatidylinositol, resulting in the absence of GPI-anchored cell membrane proteins (CD55, CD59)
  • An association exists between acquired aplastic anemia and PNH – virtually all patients with PNH  develop bone marrow dysfunction at some point in the disease
  • Pathophysiology of bone marrow failure involves abnormal red blood cell sensitivity to complement lysis

Clinical Presentation

  • Chronic hemolysis
  • Thrombophilia with anemia
    • Thromboses at various sites; most common sites are central nervous system and abdominal veins
    • Thromboses are leading cause of death
  • Bone marrow failure
  • Other signs and symptoms may include abdominal pain, iron deficiency anemia, jaundice and smooth muscle dysfunction

Diagnosis

  • Laboratory testing
    • Initial screen for hemolysis – CBC, reticulocyte count, lactate dehydrogenase (LDH), bilirubin and haptoglobin
    • Flow cytometry – evaluate for presence of CD55 and CD59
    • HAM and sugar tests may be used in screening for disease

Differential Diagnosis

  • Aplastic anemia
  • Other hemolytic diseases or processes
  • Myeloplastic disorders
  • Congenital dyserythropoietic anemia (CDA)
    • CDA is a rare inherited disease characterized by erythroblastic multinuclearity with anemia and ineffective erythropoiesis
    • Major forms – CDA I, CDA II, CDA III
    • CDA II is the most frequent
      • Autosomal recessive inheritance
      • Also known as Hereditary Erythroblast Multinuclearity with Positive Acidified Serum (HEMPAS)

Treatment

  • Minimal signs and symptoms – folic acid and thrombosis prophylaxis
  • Severe signs and symptoms – allogeneic transplants
  • Moderate disease – humanized monoclonal antibody

See Also