Oxygen gradient ektacytometry-derived biomarkers are associated with acute complications in sickle cell disease.

We investigated the potential of the Point of Sickling (PoS, the pO2 tension where red cells start to sickle), determined by oxygen gradient ektacytometry to serve as a biomarker associated with the incidence of acute sickle cell disease (SCD)-related complications in 177 children and 50 adults. In the pediatric cohort, for every 10 mmHg increase in PoS reflecting a greater likelihood of sickling, the likelihood of an individual experiencing >1 type of acute complication increased; the adjusted odds ratio (aOR) was 1.65 (p=0.006). For every 0.1 increase in EImin (reflecting improved RBC deformability at hypoxia), the aOR was 0.50 (p=0.001). In the adult cohort, for every 10 mmHg increase in PoS, the likelihood of >1 type of acute complication increased (aOR 3.00, p=0.015), although this was not significant after correcting for multiple testing. There was a trend for an association between higher PoS and greater likelihood of VOE (children aOR 1.35, p=0.071; adults aOR 2.22, p=0.050). In children only EImin was associated with VOE (aOR 0.68, p=0.036). When data of both cohorts were pooled, significant associations with PoS and/or EImin were found for all acute complications, independently, and when >1 type of acute complication was assessed. These findings indicate that oxygen gradient ektacytometry generates novel biomarkers, and provides a rationale for further development of these biomarkers in the assessment of clinical severity, evaluation of novel therapies, and as surrogate clinical trial endpoints. These biomarkers may be useful in assessing efficacy of novel therapies like pyruvate kinase activators, voxelotor and L-glutamine.