In a patient with sickle cell disease (SCD), hydroxyurea reduces sickle crisis frequency by which mechanism?
- A Increasing fetal haemoglobin (HbF) production by reactivating gamma-globin gene expression ✓
- B Direct chemical reduction of HbS polymerisation in red cells
- C Inhibiting RBC sickling by chelating intracellular calcium
- D Reducing sickling by increasing plasma viscosity
Correct answer: A. Increasing fetal haemoglobin (HbF) production by reactivating gamma-globin gene expression
Explanation
Hydroxyurea (hydroxycarbamide) is a ribonucleotide reductase inhibitor that increases HbF levels by inducing gamma-globin gene expression (via epigenetic mechanisms — nitric oxide-mediated cGMP pathway and p38 MAPK activation affecting gamma-globin transcription). Increased HbF dilutes HbS within erythrocytes and directly inhibits HbS polymerisation (HbF is not incorporated into HbS polymers). The MSH trial confirmed 44% reduction in painful crises. Hydroxyurea also reduces WBC adhesion molecules and improves nitric oxide bioavailability.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.