Heriditary spherocytosis

The following article covers most of the important points about Hereditary spherocytosis (HS) that are tested in the USMLE exam. Pay close attention to bold phrases as they are key points that appear in the exam as questions/hints.


HS is a common inherited hemolytic anemia resulting from abnormalities in the proteins of the red blood cell (RBC) membrane (mainly spectrin but also ankyrin, protein 4.2, and band 3).  


It is usually inherited in an autosomal dominant pattern, is most common in whites of Northern European descent, and is infrequent in African Americans. (Hereditary elliptocytosis (HE) is another disorder of the red cell membrane that is a common cause of inherited hemolytic anemia in African Americans.)


The membrane abnormalities of HS cause fragility of the red cell membrane with loss of surface area and a resultant spheroid shape instead of the normal biconcave appearance. The MCV is usually within the normal range for age, but may be slightly elevated if there is a brisk reticulocytosis. MCHC is high due to the relative cellular dehydration.


The abnormal RBCs become trapped in the spleen where they are eventually hemolyzed (so-called extravascular hemolysis).


This leads to an increase in LDH, unconjugated bilirubin.


Haptoglobin is a scavenger hor free hemoglobin and is normal or decreased in HS (as the hemolysis is extravascular).


Osmotic fragility is increased in HS.

Splenectomy is a common treatment but should be delayed until after school going age, if possible, due to the risk of pneumococcal sepsis. Penicillin prophylaxis is recommended for at least the first 5 years after splenectomy with some doctors recommending treatment for life.