A 22-year-old African-American man has mild chronic hemolytic anemia, splenomegaly, and numerous target cells. Smear shows rod-shaped or hexagonal red inclusions within some erythrocytes. Hemoglobin electrophoresis shows about 45% of an electrophoretically slow-moving hemoglobin. The most likely diagnosis is:

• A Sickle cell trait
• B Homozygous hemoglobin C disease ✓
• C Hemoglobin E homozygous state
• D Beta-thalassemia minor

Explanation

Hemoglobin C results from a glutamic acid to lysine substitution at position 6 of beta globin, the same codon affected in sickle hemoglobin. Reduced solubility of HbC causes crystal formation inside red cells, seen as rod-like or hexagonal inclusions, along with prominent target cells and mild hemolysis. HbE is common in Southeast Asians and shows microcytosis without crystals, sickle trait is asymptomatic, and beta-thalassemia minor shows microcytosis with raised HbA2 and no inclusions.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.