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Updated: Jul 11, 2025
Characterization of Sickling During Controlled Automated Deoxygenation with Oxygen Gradient Ektacytometry
Published on: November 5, 2019
Oxygen gradient ektacytometry-derived biomarkers are associated with acute complications in sickle cell disease
Minke A E Rab1,2, Celeste K Kanne3, Camille Boisson4,5
1Central Diagnostic Laboratory-Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Insights
Point of sickling (PoS) and red blood cell deformability (EImin) measured by ektacytometry are novel biomarkers for sickle cell disease complications. These indicators show potential for assessing disease severity and evaluating new therapies.
Area of Science:
- Hematology
- Biomarker Discovery
- Sickle Cell Disease Research
Background:
- Sickle cell disease (SCD) is characterized by red blood cell (RBC) sickling and vaso-occlusive events.
- Current biomarkers for SCD complications lack comprehensive predictive power.
- Oxygen gradient ektacytometry offers a method to assess RBC behavior under hypoxia.
Purpose of the Study:
- To investigate the point of sickling (PoS) and minimum elongation index (EImin) as biomarkers for acute SCD complications.
- To assess the association of PoS and EImin with complication incidence in pediatric and adult SCD cohorts.
- To evaluate the utility of these biomarkers in clinical severity assessment and therapy evaluation.
Main Methods:
- Oxygen gradient ektacytometry was used to measure PoS and EImin in 177 children and 50 adults with SCD.
- Statistical analysis, including adjusted odds ratios (aOR), was performed to determine associations with acute complications.
- Data from pediatric and adult cohorts were pooled for comprehensive analysis.
Main Results:
- In children, increased PoS correlated with a higher likelihood of multiple acute complications (aOR=1.65).
- Improved EImin (RBC deformability) was associated with a reduced likelihood of complications (aOR=0.50) and vaso-occlusive episodes (VOEs) in children (aOR=0.68).
- Pooled data revealed significant associations between PoS and/or EImin and all acute SCD complications.
Conclusions:
- Oxygen gradient ektacytometry provides novel, quantifiable biomarkers (PoS and EImin) for SCD.
- These biomarkers demonstrate potential for assessing clinical severity and guiding therapeutic strategies.
- PoS and EImin may serve as valuable surrogate endpoints in clinical trials for novel SCD therapies.
Abstract:
We investigated the potential of the point of sickling (PoS; the pO2 tension at which red cells start to sickle), determined by oxygen gradient ektacytometry to serve as a biomarker associated with the incidence of acute sickle cell disease-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. For every 0.1 increase in minimum elongation index (EImin; reflecting improved red blood cell deformability at hypoxia), the aOR was 0.50. In the adult cohort, for every 10 mmHg increase in PoS, we found an aOR of 3.00, although this was not significant after correcting for multiple testing. There was a trend for an association between higher PoS and greater likelihood of vaso-occlusive episodes (VOEs; children aOR, 1.35; adults aOR, 2.22). In children, only EImin was associated with VOEs (aOR, 0.68). 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 end points. These biomarkers may be useful in assessing efficacy of novel therapies like pyruvate kinase activators, voxelotor, and L-glutamine.
