A newborn is found to have hemoglobin Bart's (γ4 tetramers) on neonatal hemoglobin electrophoresis. Which of the following best explains why hemoglobin Bart's causes severe fetal anemia?

• A Gamma globin tetramers are unstable and rapidly precipitate within fetal erythrocytes
• B Hemoglobin Bart's activates complement and causes immune-mediated hemolysis
• C Hemoglobin Bart's inhibits erythropoietin production in the fetal liver
• D Hemoglobin Bart's has extremely high oxygen affinity and cannot release oxygen to tissues ✓

Explanation

Hemoglobin Bart's (γ4 tetramers) forms when all four alpha-globin genes are deleted (homozygous alpha thalassemia major), leading to hydrops fetalis. Gamma globin tetramers have an extremely high oxygen affinity (flat oxygen dissociation curve, left-shifted), making them incapable of releasing oxygen to peripheral tissues, causing severe tissue hypoxia and fetal death despite adequate oxygen binding. This is the same mechanism as hemoglobin H (β4) in adults.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.