Review Question - QID 204666

This patient's presentation is suggestive of hereditary spherocytosis. Laboratory evaluation of hereditary spherocytosis consists of a positive osmotic fragility test, elevated indirect bilirubin, negative Coombs test, a peripheral blood smear demonstrating spherocytes, and a complete blood count showing decreased MCV, increased MCHC, and an increased reticulocyte count.

Hereditary spherocytosis is an inherited autosomal dominant hemolytic anemia. It is caused by the deficiency of spectrin in RBC membranes, which leads to increased RBC membrane fragility and hemolysis through lysis in the spleen. A common presentation is a young patient with a history of gallstones who presents with anemia and splenomegaly. The increased incidence of gallstones in these patients is due to the break down of red blood cells resulting in excess indirect bilirubin. Hereditary spherocytosis must be differentiated from autoimmune hemolysis, which, unlike hereditary spherocytosis, is associated with a positive Coombs test.

Dhaliwal et al. discusses the presentation and etiologies of hemolytic anemia. Hemolysis may have either acquired or hereditary causes. Acquired causes include auto-immunity, microangiopathy, or infection. Hereditary forms are caused by disorders/mutations in RBC enzymes, RBC membranes, or hemoglobin. Hereditary spherocytosis is characterized by a family history of the disease, spherocytes on a peripheral blood smear, and a negative direct antiglobulin test.

Da Costa et al. review red blood cell membrane disorders, including hereditary spherocytosis. The RBC membrane is composed of a lipid bilayer that is linked to a spectrin skeleton. This spectrin skeleton is responsible for the flexibility and stability of the RBC membrane. Decreased membrane stability results when the lipid bilayer is not securely linked to the underlying skeleton (spectrin mutation/defect), leading to a loss of surface area as is seen in hereditary spherocytosis.

Illustration A is a peripheral blood smear from a patient with hereditary spherocytosis; note the abundant spherocytes - small, spherical RBCs lacking central pallor. Illustration B summarizes the pathophysiology of hereditary spherocytosis. Illustration C is a diagram depicting the spectrin skeleton that attaches to the lipid bilayer RBC membrane.

Incorrect Answers:
Answers 2-5: Complete blood count in hereditary spherocytosis is characterized by low MCV, elevated MCHC, and increased reticulocyte count.