Stiffening of sickle cell trait red blood cells under simulated strenuous exercise conditions

The higher risk of vaso-occlusion events and sudden death for sickle-cell trait (SCT) athletes has been speculatively ascribed to SCT red blood cell (RBC) stiffening during strenuous exercise. However, the microenvironmental changes that could induce the stiffening of SCT RBCs are unknown. To address this question, we measured the mechanical properties of and changes in SCT RBCs under deoxygenated and acidic environments, which are two typical conditions present in the circulation of athletes undertaking strenuous exercise. The results reveal that SCT RBCs are inherently stiffer than RBCs from non-SCT healthy subjects, and a lower pH further stiffens the SCT cells. Furthermore, at both normal and low pH levels, deoxygenation was found to not be the cause of the stiffness of SCT RBCs. This study confirms that the stiffening of SCT RBCs occurs at a low pH and implies that SCT RBC stiffening could be responsible for vaso-occlusion in SCT athletes during strenuous exercise.