Clinical Pearls & Morning Reports
Published November 1, 2017
Hemolytic anemia may be caused by immune, microangiopathic, or infectious processes or may result from congenital abnormalities of the erythrocyte membrane, enzymes, or hemoglobin, such as hereditary spherocytosis, glucose-6-phosphate dehydrogenase deficiency, sickle cell disease, and thalassemia. Read the latest Clinical Problem Solving Article.
Q: Why do red cells assume a spherical shape in hereditary spherocytosis?
A: Hereditary spherocytosis is the most common hemolytic anemia that is caused by a defect in red-cell membranes, with an incidence of 1 case per 2000 persons of northern European ancestry. In hereditary spherocytosis, deficiencies in membrane or associated cytoskeletal proteins from inherited gene mutations result in weakened interactions between the membrane and cytoskeleton. This leads to membrane degradation by means of vesiculation and progressive membrane loss as red cells pass through the splenic cords. The resultant spherical shape leads to decreased deformability and the characteristic appearance on the peripheral-blood smear. These spherocytes have difficulty passing through the narrow fenestrations of venous sinuses and are destroyed by macrophages within the spleen.
Figure 3. Hemolysis in Hereditary Spherocytosis.
Q: What are some of the clinical and laboratory findings associated with hereditary spherocytosis?
A: Patients with hereditary spherocytosis typically present with hemolytic anemia with jaundice, splenomegaly, an elevated mean corpuscular hemoglobin concentration, and spherocytosis. Spherocytes are nearly universal in hereditary spherocytosis but may not be seen on the peripheral-blood smear in mild cases in which the number of deformed red cells is low.
A: Traditionally, the measurement of hemolysis in a hypotonic solution (the osmotic fragility test) has been used to confirm the diagnosis in patients in whom standard laboratory features are insufficient. However, test results are normal in 10 to 20% of patients with hereditary spherocytosis and can be abnormal in patients with other causes of spherocytosis, such as autoimmune hemolytic anemia. The eosin-5-maleimide (EMA) binding test is a flow-cytometric assay that detects decreased binding of the dye EMA to the band 3 protein; deficiency of this protein is a central pathophysiological feature in hereditary spherocytosis. The EMA binding test, which has a sensitivity of 90% and specificity of 95%, is now the preferred diagnostic test in equivocal cases.
A: Splenectomy is the treatment for symptomatic moderate or severe hereditary spherocytosis. Splenectomy does not alter erythrocyte cytoskeletal abnormalities, but it eliminates the primary location of hemolysis. Current consensus discourages splenectomy in mild hereditary spherocytosis because the risks associated with the resultant immunocompromise outweigh the risk of hemolytic complications. In patients with moderate or severe hereditary spherocytosis, this risk–benefit ratio is inverted because splenectomy substantially diminishes hemolysis and the incidence of pigment gallstones.