A 24-year-old African American man presents with episodic bone pain crises, dactylitis in childhood, and a hemoglobin of 7.8 g/dL. Peripheral smear shows sickle cells. Hemoglobin electrophoresis shows HbS 90%, HbF 8%, HbA2 2.4%. He has had 4 pain crises requiring hospitalization in the past year. According to current ASH guidelines, which disease-modifying therapy should be offered?

• A Chronic transfusion therapy only
• B Voxelotor (GBT440) alone to improve HbS polymerization
• C L-glutamine supplementation
• D Hydroxyurea (HU) to increase HbF production ✓

Explanation

Hydroxyurea (hydroxycarbamide) is the first-line disease-modifying therapy for sickle cell disease in all adults with frequent pain crises (≥3/year), acute chest syndrome, or significant morbidity, per ASH 2020 guidelines and WHO recommendations. HU increases HbF through KLF1/BCL11A pathway modulation, reducing HbS polymerization and vaso-occlusive events by 50% (MSH trial). It also improves RBC hydration and reduces leukocyte adhesion. Voxelotor (anti-sickling agent) is an add-on, not a replacement for HU. L-glutamine reduces oxidative stress and is a second-line adjunct. Chronic transfusion is for specific indications (stroke prevention).

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.