In beta-thalassemia major, the principal mechanism of anemia is:

• A Absolute iron deficiency due to dietary lack
• B Autoimmune destruction of RBCs by warm IgG antibodies
• C Folate deficiency due to increased marrow turnover alone
• D Excess free alpha-globin chains precipitating in RBC precursors causing ineffective erythropoiesis and hemolysis ✓

Explanation

In beta-thalassemia major, absent or severely reduced beta-globin synthesis leaves excess free alpha-globin chains that are insoluble and precipitate within erythroid precursors, triggering apoptosis — massive ineffective erythropoiesis within the marrow. Surviving RBCs containing precipitated alpha-chains are destroyed prematurely (extravascular hemolysis). Iron overload, not deficiency, results from transfusions and increased GI absorption.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.