I. Pathophysiology & epidemiology
- Primarily affects young adults (peak incidence 25-45yo)
- 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).
- The mutation is an acquired abnormality present in a clonal population of stem cells
II. Clinical features-many and varied
- Chronic hemolytic anemia
- Due to abnormal sensitivity of RBC's to the lytic action of complement
- Venous thrombosis
- Us. of large vessels, e.g. mesenteric or hepatic vv.
- Aplastic anemia
- Acute myeloid leukemia (< 3% of pts will get)
- Sucrose hemolysis test (more sensitive) & Acid serum hemolysis ("Ham's") test (more specific); both detect lysis of erythrocytes as result of activation of complement
- 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)