A 22-year-old man with sickle cell disease (HbSS) presents with acute chest syndrome (ACS): fever, chest pain, new pulmonary infiltrate, and oxygen saturation 89% on room air. Which therapeutic intervention has been shown to reduce the severity and frequency of ACS episodes when used as chronic disease-modifying therapy?
- A Hydroxyurea increasing HbF concentration ✓
- B L-glutamine supplementation to reduce oxidative stress
- C Voxelotor (GBT440) to increase HbS-oxygen affinity
- D Crizanlizumab targeting P-selectin mediated vaso-occlusion
Explanation
Hydroxyurea is the most established disease-modifying therapy in SCD. It increases fetal haemoglobin (HbF) production through induction of gamma-globin gene expression, diluting HbS within the red cell and inhibiting sickling. Multiple landmark trials (MSH trial, HUOSCAR trial) demonstrated that hydroxyurea reduces the frequency of painful vaso-occlusive crises, ACS episodes, hospitalizations, and transfusion requirements, and reduces mortality. For ACS specifically, exchange transfusion is used for acute severe episodes. Voxelotor increases HbS oxygen affinity (reducing sickling) and crizanlizumab prevents P-selectin-mediated vaso-occlusion — both are approved for reducing VOC but have fewer data specifically for ACS prevention compared to hydroxyurea.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.