NBME Form 27 Practice Test 2026 - Free NBME Sample Questions and Study Guide

In patients with sickle cell disease who are treated with hydroxyurea, the observation of large pale red blood cells (RBCs) alongside a mix of sickle and normal shapes is indicative of the treatment’s effects on the erythropoiesis process and the overall blood cell morphology. Hydroxyurea works primarily by increasing fetal hemoglobin (HbF) levels, which can lead to the reduction of sickle-shaped cells and a decrease in hemolytic episodes.

When hydroxyurea is administered, it stimulates the production of fetal hemoglobin, which inhibits the sickling process by reducing the overall concentration of hemoglobin S in RBCs. As a result, the peripheral blood smear may reveal a more significant proportion of normal-shaped cells, alongside larger pale RBCs due to increased mean corpuscular volume (MCV) seen in the presence of macrocytosis.

The presence of both sickled and normal-shaped RBCs reflects the ongoing sickle cell pathology while indicating the positive therapeutic effect of hydroxyurea. This combination of increased fetal hemoglobin and altered red blood cell morphology enhances the oxygen-carrying capacity of the blood and reduces the risk of vaso-occlusive crises. This characteristic finding effectively captures the impact of