Beta-thalassemia major leads to extramedullary hematopoiesis primarily in the liver, spleen and skull (hair-on-end appearance). The immediate driver of extramedullary hematopoiesis is:

• A Severe ineffective erythropoiesis causing marrow expansion that overflows to extramedullary sites ✓
• B Iron overload damaging the bone marrow cavity
• C Splenomegaly sequestering stem cells that then seed extramedullary sites
• D Chronic transfusions suppressing normal erythropoiesis and redirecting stem cells

Explanation

In beta-thalassemia major, excess unpaired alpha-globin chains precipitate within erythroblasts causing massive ineffective erythropoiesis. Profound anemia drives erythropoietin secretion, resulting in extreme marrow expansion and overflow to extramedullary sites (liver, spleen, paravertebral tissues). The skull changes ('hair-on-end' on X-ray) reflect expansion of calvarial marrow spaces.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.