Which of the following is a mechanism of action for hydroxycarbamide in sickle cell disease?

• A. Increasing the number of RBCs containing foetal haemoglobin
• B. Helps to keep RBCs well-hydrated and reducing their stickiness
• C. Reduction in WBC count which produce chemicals that can cause inflammation and trigger sickling
• D. Decreases RBC oxygen affinity

Answer: (A)

Hydroxycarbamide mainly works by boosting the production of fetal hemoglobin (HbF) in red blood cells. HbF doesn’t sickle like HbS, so when HbF levels rise, it dilutes HbS within the cell and prevents deoxygenated HbS from polymerizing. With less polymer formation, red cells stay more flexible and are less likely to clump together and block small vessels, which lowers painful crises and other sickling complications.

The idea of keeping red cells well-hydrated or reducing their stickiness isn’t how this drug acts. It can also cause a decrease in white blood cells, which may reduce inflammatory factors that contribute to crises, but that effect is secondary to HbF induction. It certainly doesn’t decrease oxygen affinity of hemoglobin; lowering oxygen affinity would make sickling worse, not better.