A 25-year-old woman from West Africa has haemoglobin electrophoresis showing HbS 80%, HbF 18%, HbA 0%, HbA2 2%. She presents in a sickle cell crisis. Concerning hydroxyurea therapy for sickle cell disease, which statement is MOST accurate?
- A Hydroxyurea increases HbF (foetal haemoglobin) production by reactivating gamma-globin gene expression, thereby reducing sickling and crisis frequency ✓
- B Hydroxyurea increases HbS production, reducing viscosity through dilution
- C Hydroxyurea is contraindicated in sickle cell disease due to bone marrow suppression
- D Hydroxyurea acts by chelating free iron in sickle erythrocytes
Explanation
Hydroxyurea (hydroxycarbamide) is the cornerstone pharmacological therapy for sickle cell disease. It inhibits ribonucleotide reductase and through epigenetic mechanisms reactivates gamma-globin gene expression, increasing HbF (foetal haemoglobin) synthesis. HbF inhibits HbS polymerisation, reducing the frequency of vaso-occlusive crises, acute chest syndrome, and hospitalisations, as demonstrated in the landmark MSH (Multicenter Study of Hydroxyurea in Sickle Cell Anemia) trial. HbF levels of even 15–20% significantly reduce sickling. Myelosuppression is a monitored but manageable adverse effect.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.