The patient is admitted to the hospital and receives opioid analgesics and intravenous fluids. He has no evidence of active infection. His hemoglobin electrophoresis results are consistent with sickle cell disease (hemoglobin SS). Further laboratory evaluation shows a mean corpuscular volume of 113 µm³ and a reticulocyte index of 1.5, which is low given the patient's severe anemia. Which of the following is the most likely cause of this patient's macrocytosis?

Question

Quizplus · Accepted Answer

This patient has macrocytic anemia (mean corpuscular volume [MCV] >100 µm³). Severe macrocytosis (MCV >110 µm³) is usually due to megaloblastic anemia, a subtype of macrocytic anemia caused by impaired DNA synthesis. Cytoplasmic components then accumulate within the slowly dividing erythrocytes, producing cells that are larger than normal (macrocytes). Patients with sickle cell disease (SCD) or other hemolytic anemias have increased folic acid requirements due to increased erythrocyte turnover. As such, they are prone to developing relative folic acid deficiency and megaloblastic anemia. (Choice A) Extramedullary erythropoiesis can occur in SCD and lead to an elevated reticulocyte count and MCV, as the reticulocytes produced are larger than those released by the bone marrow. However, this patient's low reticulocyte index (representing the reticulocyte percentage corrected for the degree of anemia) suggests an inadequate response to anemia and a lack of erythropoiesis. (Choice C) Patients with SCD may receive multiple transfusions for treatment of severe or symptomatic anemia. Transfusion related iron overload can cause severe liver disease, but would be unlikely to produce an MCV >110 µm³. (Choice D) Macrocytosis can occur in liver failure due to an increase in circulating phospholipids and cholesterol that adsorb onto erythrocytes, resulting in membrane expansion. However, liver-associated macrocytosis is generally mild (<110 µm³) and this patient does not have any findings to suggest advanced liver disease (eg, ascities/edema, bleeding). (Choice E) A disease of the elderly, myelodysplastic syndrome can cause macrocytic anemia. In the setting of a young patient with SCD and hemolytic anemia, however, folic acid deficiency is much more likely. Educational objective: An MCV >110 µm³ is highly suggestive of megaloblastic anemia, such as that caused by folic acid or vitamin B₁₂ deficiency. Patients with chronic hemolytic anemia have increased folic acid requirements due to increased erythrocyte turnover and are predisposed to developing macrocytosis.

The Patient Is Admitted to the Hospital and Receives Opioid