A 30-year-old man is found to have HbH disease (three alpha-globin gene deletions, genotype --/-α). Peripheral smear shows hypochromic microcytic cells with HbH inclusion bodies after brilliant cresyl blue staining. What is the clinical severity compared to the two major forms of alpha-thalassemia?
- A Silent carrier state with no anemia
- B Moderate chronic hemolytic anemia that is transfusion-independent in most cases but may worsen with infections or oxidant stress ✓
- C Uniformly lethal in utero (hydrops fetalis)
- D Clinically identical to beta-thalassemia major requiring monthly transfusions
Correct answer: B. Moderate chronic hemolytic anemia that is transfusion-independent in most cases but may worsen with infections or oxidant stress
Explanation
HbH disease (3-gene alpha-thalassemia, --/-α) produces moderate hemolytic anemia from accumulation of beta4 tetramers (HbH) which precipitate as inclusion bodies damaging erythrocytes. Patients are usually transfusion-independent but decompensate with infections or oxidant exposure. Silent carrier (1 deletion, -α/αα) and alpha-thalassemia trait (2 deletions) cause minimal or no anemia. Hydrops fetalis (Hb Bart's disease) results from 4-gene deletion with only gamma4 tetramers.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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