Sickle‐cell haemoglobin polymerization: is it the primary pathogenic event of sickle‐cell anaemia?

Sickle cell anaemia is associated with a mutant haemoglobin, HbS, which forms polymers in the red blood cells of patients. The primary role of the HbS polymerization for the pathophysiology has been questioned: observations in patients and model organisms contradict deterministic scenarios of sickling crises triggered by polymerization. However, results with knock-out sickle-cell mice, which were cured by delaying HbS polymerization, reconfirm...