A 28-year-old woman of West African origin has mild chronic hemolytic anemia with splenomegaly. Smear shows numerous target cells and occasional rod-shaped or hexagonal intracellular inclusions. Hemoglobin electrophoresis shows HbA 52%, HbC 46%, HbA2 2%. These inclusions form because of which property of the abnormal hemoglobin?
- A Polymerization of deoxygenated hemoglobin tetramers
- B Reduced solubility and crystallization of the beta globin variant ✓
- C Precipitation of excess alpha globin chains
- D Oxidative denaturation of globin into Heinz bodies
Explanation
Hemoglobin C results from a glutamic acid to lysine substitution at position 6 of beta globin, the same site as the sickle mutation. The substituted molecule has markedly reduced solubility and forms intraerythrocytic crystals that appear as rod-like or hexagonal inclusions, along with prominent target cells from membrane redundancy. Polymerization of deoxygenated tetramers describes HbS, excess alpha chain precipitation describes beta-thalassemia, and Heinz bodies describe unstable hemoglobins and G6PD deficiency. Homozygous HbC disease is clinically much milder than sickle cell disease.
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.