A 28-year-old woman of Mediterranean descent presents with hemolytic anemia, splenomegaly, and a history of gallstones. Which finding best distinguishes β-thalassemia major from hereditary spherocytosis?

Distinguishing β-Thalassemia Major from Hereditary Spherocytosis

Hematologic and Morphologic Comparison

The microcytic, hypochromic picture with target cells is pathognomonic for β-thalassemia major. The MCV is markedly reduced (60–70 fL) due to defective hemoglobin synthesis, whereas hereditary spherocytosis has a normal or near-normal MCV with spherocytic morphology.

Target cells (codocytes) in thalassemia result from the combination of microcytosis and reduced hemoglobin content — the RBC appears as a "target" with a dense central core surrounded by a pale ring. This is absent in hereditary spherocytosis, where RBCs are dense and spherical.

"THALASSEMIA = TARGET cells" — The morphologic hallmark of thalassemia is target cells due to microcytosis and hypochromia.

Both conditions can present with hemolytic anemia, splenomegaly, and gallstones, but the blood smear morphology and MCV immediately distinguish them. Thalassemia major requires transfusion dependence from infancy; hereditary spherocytosis is often managed conservatively or with splenectomy.

Robbins 10e Ch 13