PS1523 THE OXYGENSCAN: A COMPREHENSIBLE FUNCTIONAL RED BLOOD CELL TEST TO MONITOR TREATMENT EFFICACY IN PATIENTS WITH SICKLE CELL DISEASE
Authors: Rab M. , Houwing M. , Nur E. , de Pagter A. , Bos J. , van Oirschot B. , Bartels M. , Cnossen M. , van Wijk R. , van Beers E. 
Published: June 2019

Background:

Sickle cell disease (SCD) has multifactorial and complex pathophysiology leading to vaso‐occlusive crises, inflammation, chronic hemolytic anemia and extensive organ damage, resulting in increased morbidity and mortality. To date, there are no laboratory parameters or assays available that can predict disease severity or directly monitor treatment effects.

Aims:

To validate the oxygenscan, a new method to quantify sickling behavior, as a functional assay to monitor patients with SCD treated with hydroxyurea (HU).

Methods:

This is an observational multicenter study in children and adults with SCD who started HU treatment. Blood samples were obtained at baseline, and after 1, 3 and 6 months for complete blood count, hemoglobin electrophoresis and oxygenscans on the Laser Optical Rotational Red Cell Analyzer (Lorrca, Zwaag, The Netherlands). The oxygenscan measures red blood cell deformability (expressed as Elongation Index – EI) as a function of oxygen tension (Rab et al, AJH 2019 in press). Key read out parameters are: EImax: maximum elongation during deoxygenation, EImin: minimum elongation after deoxygenation, Point of Sickling (PoS): pO2 (mmHg) at which >5% decrease of EImax during deoxygenation is observed, Slope: slope of the linear part of the deoxygenation curve (Figure 1A).

Results:

Thirteen patients starting on HU were enrolled. Of these, four patients were followed up to 6 months and seven patients up to 3 months. At 3 months after starting HU treatment all four key oxygenscan parameters were significantly different compared to baseline (all p < 0.05, Figure 1B and C) which stabilized and were comparable to curves measured after 6 months.

Levels of fetal hemoglobin (HbF) correlate best with EImin (r = 0.759, p < 0.0001, low values indicate poor deformability under deoxygenated conditions). High absolute reticulocyte counts (ARC) showed a clinically unfavorable increase of oxygen concentration at which RBCs start to sickle (termed PoS), than with lower ARC (Figure 1D). The Slope showed a weak inverse correlation with mean corpuscular hemoglobin concentration (MCHC, r = −0.406, p = 0.016), indicating that increased cellular density accounts for a lower Slope, which increases upon HU treatment. EImin was also associated with mean corpuscular volume (MCV) with a weak correlation (r = 0.451, p = 0.006), which indicates that with an increase of MCV also EImin increases. Our results indicate that oxygenscan parameters including EImin and PoS correlate with established laboratory parameters used in clinical practice to determine treatment efficacy. Although correlations with PoS and Slope were less strong, we observed a significant change upon HU treatment. This suggests involvement of other crucial factors influencing sickling such as intracellular 2,3‐diphosphoglycerate (2,3‐DPG) levels and pH. Based on the results of individual oxygenscans, treatment decisions were made in at least two patients, who showed a clear worsening of the oxygenscan during the 6 months visit. This prompted the physician to review compliance and increase the dosage of HU. These findings show that the oxygenscan can provide additional information and can fill the clinical need for a reliable functional assay in SCD.

Summary/Conclusion:

The oxygenscan is a versatile and efficient method to monitor HU treatment efficacy in patients with SCD. It is a functional assay that simultaneously determines various RBC features that contribute to individual sickling tendency of patients. It is of added value in personalized treatment of patients with SCD, in particular in titration of HU in children.

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