A 19-year-old woman comes to the office due to exertional dyspnea and intermittent lightheadedness. On examination, mucosal pallor is present. Laboratory studies reveal a red blood cell count of 3.5 million/mm³ and a hemoglobin concentration of 8.5 g/dL. Peripheral smear is shown in the image below: Which of the following findings are most likely present in this patient?

Question

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11ec160b_3af3_f329_9249_b1ff86963aec_MD0001_00 This patient's dyspnea, lightheadedness, and mucosal pallor are likely due to symptomatic anemia. A number of underlying processes can cause anemia, but the differential diagnosis can usually be narrowed by concurrent clinical data. In this case, the peripheral blood smear demonstrates hypochromic, microcytic erythrocytes and a variety of erythrocyte shapes (poikilocytosis), raising strong suspicion for severe iron deficiency anemia (IDA). Young women often develop IDA from heavy menstruation. Patients with severe IDA do not have enough iron to generate adequate hemoglobin for each erythrocyte, which results in low mean corpuscular hemoglobin concentration (hypochromia) and small erythrocyte size (microcytosis). Interstitial fibroblasts in the peritubular capillaries and proximal convoluted tubule of the kidney detect the reduced oxygen carrying capacity of the blood (mild tissue hypoxia) and increase erythropoietin release to drive the generation of new erythrocytes. However, new erythrocytes cannot be produced at a level to compensate for the anemia due to insufficient serum iron; therefore, patients typically have minimal reticulocytes and low red blood cell counts in the peripheral blood. (Choice A) Transferrin is a serum protein that binds free iron. The concentration of transferrin is increased in IDA (to maximize free iron scavenge), but the amount of iron bound to it is reduced, leading to a low transferrin saturation on laboratory evaluation. (Choices B, C, and E) Hepcidin is a small peptide released by the liver in response to inflammation. It binds to and inhibits iron channels on the surface of enterocytes and on reticuloendothelial macrophages, which reduces iron absorption in the gut and reduces iron release from the reticuloendothelial system (the primary site of iron recycling). Because IDA is not mediated by inflammation, hepcidin levels are typically low; this increases gastrointestinal iron absorption and iron release from the reticuloendothelial system (eg, splenic macrophages). In contrast, anemia of chronic disease is associated with very high levels of hepcidin (and other inflammatory cytokines), which reduces iron availability for erythrocytosis despite adequate total body stores of iron. Patients with anemia of chronic disease typically have normocytic anemia and normochromia (not hypochromia). Educational objective: Patients with severe iron deficiency anemia (IDA) typically have evidence of hypochromic, microcytic erythrocytes on peripheral blood smear with poikilocytosis. Laboratory studies will reveal low red blood cell count, low hepcidin, and high transferrin. Although erythropoietin is markedly elevated in IDA, there is not enough iron to efficiently generate erythrocytes; therefore, reticulocyte count is low.

A 19-Year-Old Woman Comes to the Office Due to Exertional