Hereditary spherocytosis is a disorder of the red blood cell membrane, leading to chronic hemolytic anemia. Normally, the red blood cell is a biconcave disk with a diameter of 7–8 mcm. The red blood cells must be both strong and deformable—strong to withstand the stress of circulating for 120 days and deformable so as to pass through capillaries 3 mcm in diameter and splenic fenestrations in the cords of the red pulp of approximately 2 mcm. The red blood cell membrane skeleton, made up primarily of the proteins spectrin and actin, gives the red cells these characteristics of strength and deformability.
In hereditary spherocytosis, the membrane defect is an abnormality in spectrin, actin, or other red blood cell membrane proteins, such as band 3 or protein 4.2; these proteins provide most of the scaffolding for the red blood cell membranes. The result is a decrease in surface-to-volume ratio that results in a spherical shape of the red blood cell. These spherical red blood cells are less deformable and unable to pass through the small fenestrations in the splenic red pulp. Hemolysis takes place because of trapping of red blood cells within the spleen and their premature removal by splenic macrophages.
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 ...