Session: 101. Red Cells and Erythropoiesis, Excluding Iron: Poster II
Hematology Disease Topics & Pathways:
Research, Genetic Disorders, Clinical Research, Diseases, Human, Study Population
Aim: To explore possible correlations between established and novel diagnostic outcome parameters and clinical severity in a well-defined cohort of HS patients.
Methods: This monocenter retrospective cohort study involves patients diagnosed with HS upon referral to our department between 2012 and 2023. Clinical characteristics, routine and advanced diagnostic laboratory parameters, and genotype were evaluated. Clinical severity was classified as previously described, based on parameters such as hemoglobin, reticulocyte percentage and bilirubin1. The following laboratory tests were included: routine hematological parameters (Cel-Dyn Sapphire or Alinity hq), EMA binding test, osmotic fragility test (OFT) and osmotic gradient ektacytometry (osmoscan, Lorrca MaxSis). The latter technique was also explored for other parameters than the commonly used EImax, Ohyper and Omin. NGS gene panel analysis was used for molecular diagnosis. Differences between groups were determined using either Chi-squared test, unpaired t-test or Mann-Whitney U test and correlations using point-biserial, Pearson’s or Spearman’s test via GraphPad Prism.
Results: Eighty-two non-splenectomized patients were included. Thirty-five of these (42.7%) were classified as mild, and forty-seven as moderate-severe (57.3%)). Demographic characteristics nor genotype differed significantly, albeit SPTB variants occurred more frequently in the moderate-severe group (15 vs. 4 in the mild group). Expectedly, both reticulocyte count and EImax correlated with clinical severity. RBC distribution width (RDW) correlated moderately, suggesting greater RBC heterogeneity (r=0.606, p<0.0001) is associated with a more severe clinical phenotype. Similarly, EMA binding test results correlated with clinical severity (r=0.390, p<0.001), indicating more pronounced membrane loss in clinically more severe patients. We further evaluated three novel osmoscan parameters (Figure 1): EIO290, the elongation index (EI) at physiologic isotonicity, which correlated with clinical severity (r=-0.500, p<0.0001), and also with EImax (r=0.856, p<0.0001). The Omin-width and Omax-width, defined as the difference in osmolality between the intersection points of y=EImin or EImax +/- 0.05 and the osmoscan curve. This assesses the effect of changes in osmolality on EImin or EImax, respectively. Omin-width correlated with RDW (r-0.439, p<0.0001), OFT results (N=30, r=0.671, p<0.0001) and clinical severity (r=0.390, p<0.001). Omax-width correlated with clinical severity (r=-0.375, p<0.001) and strongly with percentage of hyperchromic cells (N=76, r=-0.751, p<0.0001), yet weakly with RDW (-0.273, p<0.05). All significant correlations with clinical severity are displayed in Figure 2.
Conclusion: In this study, a number of routine and advanced diagnostic laboratory parameters were found to correlate with clinical severity in HS. Omin-width and Omax-width are novel osmoscan-derived biomarkers that correlated with RDW, hyperchromic cells (Omax-width), OFT results (Omin-width) and clinical severity. EIO290, another novel osmoscan-derived biomarker, also correlated with clinical severity, although not stronger than EImax and AUC. The biomarkers identified in this study, together with patient-reported outcome measures (PROMs), could be used to revise the previously established severity classification system and thereby aid in stratifying clinical severity and subsequent clinical decision-making.
References:
- Eber, S. W., Armbrust, R., & Schröter, W. (1990).
Disclosures: De Wilde: Agios Pharmaceuticals, Inc.: Research Funding. Van Beers: Pfizer, Inc.: Research Funding; Novartis AG: Research Funding; RR Mechatronics: Research Funding; Agios Pharmaceuticals, Inc. Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Rab: Axcella Therapeutics, Inc.: Research Funding; RR Mechatronics: Research Funding; Pfizer, Inc.: Research Funding; Agios Pharmaceuticals, Inc.: Consultancy, Research Funding. van Wijk: Pfizer, Inc.: Consultancy, Research Funding; Agios Pharmaceuticals, Inc.: Consultancy, Research Funding; Axcella Therapeutics, Inc.: Research Funding; RR Mechatronics: Research Funding.
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