H e r e d i t a r y S p h e r o c y t o s i s
Clinical features
• Classic triad: mild anemia, intermittent jaundice, splenomegaly.
• Relatively common (1 in 5000 people of northern European descent).
• Variable age of onset, severity.
• Anemia often exaggerated during "crises", most often precipitated by
infection with parvovirus B19 (fifth disease).
Pathogenesis
• Basic defect: membrane cytoskeleton has defective spectrin content or
function. This leads to altered membrane properties (loss of surface area,
altered membrane lipids/proteins).
• The spectrin defects result in red cell destruction - but only in the presence
of the spleen!
Morphology
• Mild normochromic, normocytic anemia.
• Numerous spherocytes.
• Evidence of accelerated hematopoiesis (polychromatophilia, normoblasts).
Therapy
• Splenectomy (curative).
• If splenectomy not possible, may need red cell transfusions during crises.
Other hemolytic anemias due to inherited membrane abnormalities
Hereditary elliptocytosis
• Pathogenesis: Spectrin abnormality (mutation different than that of HS).
• Clinical Features: Mild anemia, usually fully compensated.
May have exacerbations during crises, however.
Homozygotes have chronic, transfusion-dependent anemia, which is
responsive to splenectomy (like patients with HS).
• Morphology: Numerous elliptocytes.
Hereditary pyropoikilocytosis
• Pathogenesis: Mutant spectrin won't stick to itself, is rapidly degraded
• Clinical Features: Mild anemia with crises, like HS and HE.
• Morphology: Bizarrely-shaped red cells! (look like red cells that have been
exposed to heat – thus the name "pyro".)
