PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

I. Pathophysiology & epidemiology

  1. Primarily affects young adults (peak incidence 25-45yo)
  2. Seems to be due to a loss of a variety of cell surface proteins that are normally attached to cell membrane via a glycosyl-phosphatidyl-inositol molecule; in PNH, synthesis of this molecule is impeded by a mutation in the gene for one of its synthetic enzymes (PIG-A).
  3. The mutation is an acquired abnormality present in a clonal population of stem cells

II. Clinical features-many and varied

  1. Chronic hemolytic anemia
  1. Due to abnormal sensitivity of RBC's to the lytic action of complement
  1. Venous thrombosis
  1. Us. of large vessels, e.g. mesenteric or hepatic vv.
  1. Aplastic anemia
  2. Acute myeloid leukemia (< 3% of pts will get)

III. Diagnosis

  1. Sucrose hemolysis test (more sensitive) & Acid serum hemolysis ("Ham's") test (more specific); both detect lysis of erythrocytes as result of activation of complement
  2. Flow cytometric assay for direct detection of loss of GPI-linked proteins on erythrocytes and WBC's (more sensitive and specific than the abov methods)

(Source: UW Lab Medicine Newsletter; Fall 1997)