A 22-year-old patient with homozygous sickle cell disease (HbSS) is on hydroxyurea but has two acute painful crises requiring hospitalisation in the past 12 months. Which newer therapy, approved by FDA in 2019, works by activating pyruvate kinase in red blood cells to reduce HbS polymerisation by increasing 2,3-BPG consumption?

• A Crizanlizumab (anti-P-selectin monoclonal antibody)
• B L-glutamine
• C Mitapivat (pyruvate kinase activator)
• D Voxelotor (HbS polymerisation inhibitor) ✓

Explanation

Voxelotor (GBT440) works by binding to haemoglobin and allosterically stabilising the oxy (R) conformation of HbS, shifting the O2 dissociation curve leftward and preventing HbS polymerisation in the deoxy state. The HOPE trial demonstrated improved haemoglobin levels and reduced haemolysis markers. Crizanlizumab (anti-P-selectin) prevents vaso-occlusion by blocking P-selectin-mediated adhesion of sickle cells to endothelium. L-glutamine reduces oxidative stress in sickle cells. Mitapivat is a pyruvate kinase activator approved for hereditary haemolytic anaemia (pyruvate kinase deficiency) and is being studied in SCD but is not the drug described.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.