The presence of spherocytes in the peripheral blood smear suggests either hereditary spherocytosis (HS) or autoimmune hemolytic anemia (AIHA). Spherocytes are spherical RBCs without an area of central pallor and are usually slightly smaller in size than the average red cell. Spherocytes have increased osmotic fragility (because of decreased distensibility associated with reduced surface membrane area) in hypotonic saline, and this test (osmotic fragility test) is positive in HS and in AIHA. The direct antiglobulin (Coombs) test distinguishes between them; the result is positive in AIHA and negative in HS.
By permission of the publisher. From Tefferi A, Li C. In Atlas of Clinical Hematology . Edited by JO Armitage. Philadelphia, Current Medicine, 2004.