A 26-year-old woman comes to the office for a follow-up appointment. She has a history of immune thrombocytopenia that failed to improve with glucocorticoid therapy. The patient underwent splenectomy 6 months ago, which resulted in improved platelet counts. She received the recommended vaccinations after her surgery and currently feels well. Physical examination shows no abnormalities. A peripheral blood smear reveals many red blood cells of a specific morphology as indicated by the arrow below.
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An increase in which of the following features best explains the presence of these abnormal cells?
Target cells are red blood cells with a dark center, a surrounding halo of pallor, and a dark peripheral ring. They form in erythrocytes with an excessive surface area-to-volume ratio, which results in redundant erythrocyte cell membrane folding upon itself (thereby creating the appearance of a target). Target cells occur in the following conditions:
Reduced erythrocyte cell volume from deficient hemoglobin synthesis (eg, thalassemia, iron deficiency) or structural mutations to hemoglobin (eg, sickle cell)
Excessive erythrocyte cellular membrane due to greater cholesterol-to-phospholipid ratios (eg, obstructive liver disease) or splenectomy
Macrophages in the red pulp of the spleen remove excess membrane from red cells, a process called "splenic conditioning." Patients who undergo splenectomy are unable to prune erythrocytes and generally develop target cells a few weeks following the procedure. However, over time, macrophages in nonsplenic tissue (eg, liver) take up the task of pruning erythrocytes, which typically eliminates (or diminishes) the presence of target cells in the circulation.
(Choice A) Pappenheimer bodies are aggregated iron deposits in erythrocytes that are often seen in patients with sideroblastic anemia. They appear as dark blue inclusions.
(Choice B) Howell-Jolly bodies are clusters of DNA remnants in erythrocytes due to hyposplenism or asplenism (the spleen usually removes the DNA remnants). They appear as peripheral, round, dark purple, blue, or red inclusions.
(Choice C) Heinz bodies are aggregates of denatured hemoglobin that may be present in erythrocytes when patients have glucose-6-phosphate dehydrogenase deficiency or thalassemia. They cannot be seen on routine staining.
(Choice D) Spherocytes have low surface area-to-volume ratios and are more susceptible to osmotic stress. They are seen most commonly in hemolytic anemia and hereditary spherocytosis and appear as dense, round red blood cells. Target cells are less susceptible to osmotic stress than normal red blood cells or spherocytes due to their excess membrane.
(Choice E) Basophilic stippling is blue granules dispersed within the cytosol of erythrocytes due to precipitated ribosomes. It is seen most commonly in thalassemias, alcohol use disorder, and lead/heavy metal poisoning.
Educational objective:
Target cells form when erythrocytes have reduced cell volume (eg, thalassemia, iron deficiency) or excessive membrane (eg, obstructive liver disease, postsplenectomy). Patients who undergo splenectomy usually develop target cells because the spleen is the primary organ that prunes excessive red cell membrane.