Dalcetrapib decreases red blood cell sickling propensity in sickle cell disease

The aim of the present study was to compare the effects of dalcetrapib and voxelotor on the rheology of red blood cells (RBCs) from sickle cell patients, as well as on hemoglobin oxygen affinity. Oxygen gradient ektacytometry was used to determine RBC deformability in normoxia and hypoxia, as well as the propensity of RBCs to sickle. Hemoglobin oxygen affinity was also measured following dalcetrapib and voxelotor incubation. Both voxelotor and dalcetrapib increased RBC deformability in hypoxia and decreased the propensity of RBCs to sickle under deoxygenation. However, in contrast to voxelotor, the affinity of hemoglobin S (HbS) to oxygen was not affected by dalcetrapib. The combination of both voxelotor and dalcetrapib led to greater RBC rheological improvement. Our findings suggest that dalcetrapib could inhibit RBC sickling during deoxygenation.