A 24-year-old woman with sickle cell anaemia (HbSS) has had three painful crises in the past year. She is not on any disease-modifying therapy. Her current haemoglobin is 7.1 g/dL and fetal haemoglobin (HbF) is 4%. According to the ASH 2020 guidelines, which intervention is recommended as first-line disease-modifying therapy to reduce vaso-occlusive crises?
- A Crizanlizumab (anti-P-selectin monoclonal antibody)
- B Voxelotor (HbS polymerisation inhibitor)
- C Chronic transfusion programme
- D Hydroxyurea (hydroxycarbamide) — oral cytoreductive agent that increases HbF ✓
Explanation
Hydroxyurea (HU) remains the cornerstone first-line disease-modifying therapy for sickle cell disease in patients with ≥ 3 vaso-occlusive crises per year. HU increases HbF by activating alternate erythropoiesis and activating the fetal globin gene promoter, reducing HbS polymerisation, sickling, and adhesion. Long-term data (the MSH and BABY HUG trials) show HU reduces mortality, acute chest syndrome, stroke, and hospitalisations. Crizanlizumab (anti-P-selectin; SUSTAIN trial) is a second-line add-on approved for ≥ 1 crisis/year. Voxelotor (HOPE trial) raises haemoglobin but is primarily for anaemia, not crises. Chronic transfusion is reserved for specific indications (stroke prevention, acute chest).
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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