Hereditary spherocytosis is an autosomal dominant disease of variable severity. It is often diagnosed during childhood, but milder cases may be discovered incidentally late in adult life. Anemia may or may not be present, since the bone marrow may be able to compensate for shortened red cell survival. Severe anemia (aplastic crisis) may occur in folic acid deficiency or when bone marrow erythropoiesis is temporarily impaired by infection. Chronic hemolysis causes jaundice and pigment (calcium bilirubinate) gallstones, leading to attacks of cholecystitis, and medial malleolar skin ulcers. Examination may reveal icterus and a palpable spleen.
The anemia is of variable severity, and the hematocrit may be normal. Reticulocytosis is always present. The peripheral blood smear shows the presence of spherocytes, small cells that have lost their central pallor. Hereditary spherocytosis is the only important disorder associated with microcytosis (sometimes normocytic) and an increased MCHC, often greater than 36 g/dL. As with other hemolytic disorders, there may be an increase in indirect bilirubin. The Coombs test is negative (see section on Autoimmune Hemolytic Anemia).
Because spherocytes are red cells that have lost some membrane surface, they are abnormally vulnerable to swelling induced by hypotonic media. Increased osmotic fragility merely reflects the presence of spherocytes and does not distinguish hereditary spherocytosis from other spherocytic hemolytic disorders such as autoimmune hemolytic anemia. In some laboratories, the osmotic fragility test has been supplanted by ektacytometry, which has the advantages of better reliability and the ability to distinguish spherocytes from other red blood cell abnormalities such as elliptocytes. EMA (eosin-5’ maleimide) binding by flow cytometry is another diagnostic tool.