A 3-year-old child presents with pallor, splenomegaly, and recurrent vaso-occlusive crises. Haemoglobin electrophoresis shows predominantly HbS with a small amount of HbF and no HbA. Parents are told about hydroxyurea therapy. The primary mechanism of benefit of hydroxyurea in sickle cell disease is:

• A Induction of HbF synthesis by inhibiting ribonucleotide reductase, reducing HbS concentration ✓
• B Direct inhibition of HbS polymerisation by binding to the beta-globin chain
• C Reduction of reticulocyte count by suppressing erythropoiesis
• D Chelation of iron to reduce haemolysis

Explanation

Hydroxyurea induces foetal haemoglobin (HbF) production by inhibiting ribonucleotide reductase; increased HbF interferes with HbS polymerisation because HbF-containing tetramers (alpha2-gamma2) do not participate in deoxyHbS polymer formation. The resulting dilution of HbS concentration reduces sickling, vaso-occlusion, and haemolysis. Hydroxyurea does not directly bind beta-globin or chelate iron; it also has secondary effects on leukocyte adhesion and nitric oxide generation.

Reference: Ghai Essential Pediatrics, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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