In beta-thalassemia major, the primary mechanism producing severe anemia is:

• A Autoimmune destruction of RBCs by anti-Rh antibodies
• B Reduced hepcidin leading to iron overload without affecting hemoglobin synthesis
• C Deletion of alpha-globin genes reducing total hemoglobin content
• D Excess unpaired alpha-chains precipitating within erythroid precursors causing massive ineffective erythropoiesis ✓

Explanation

In beta-thalassemia, absent or reduced beta-chain synthesis leads to unpaired alpha-chains that are unstable and precipitate within erythroid precursors in the bone marrow, causing massive ineffective erythropoiesis (intramedullary destruction before cells are released). Surviving RBCs with inclusions are destroyed in the spleen. The erythroid hyperplasia leads to bone expansion and extramedullary hematopoiesis. Alpha-globin gene deletions characterize alpha-thalassemia.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.