Red Blood Cell Metabolism in Hemoglobinopathies of Sickle Cell Disorder and Thalassemia Patients in the State of Odisha

BACKGROUND: Hemoglobinopathies are highly prevalent in Odisha, India and are associated with red blood cell (RBC) physiology through chronic hemolysis, oxidative stress, and altered energy metabolism. However, data on RBC glucose metabolism and redox status on hemoglobin variants are limited. AIMS: The aim of this study was to access the glucose metabolism and oxidative stress markers among hemoglobinopathy subtypes and identify HbVariant-specific metabolic signatures. MATERIALS AND METHODS: This cross-sectional study enrolled 490 adults (18–60 years) with HbAA, HbAS, HbSS, HbS/β-thalassemia, HbSD Punjab , HbSE, and β-thalassemia. Hemoglobin variants were identified using cation-exchange high-performance liquid chromatography. Hematological and biochemical markers, glycolytic intermediates, RBC adenosine triphosphate (ATP), NADP/NADPH, G6PD activity, malondialdehyde, and glutathione were measured using standardized assays. An unpaired Student’s t -test with a Tukey–Kramer post hoc multiple comparisons test was performed using GraphPad Prism (v. 5), and multivariate clustering analysis, including heat maps and principal component analysis, was performed using MetaboAnalyst 6.0. A P < 0.05 is considered significant. RESULTS: Hemoglobinopathies, such as HbSS, HbS/β-thalassemia, and β-thalassemia, presented significant anemia, increased hemolysis (lactate dehydrogenase and bilirubin), and oxidative stress markers (increased malondialdehyde and declined reduced glutathione levels ( P < 0.0001)). Metabolic profiling showed higher levels of lactate, different pyruvate levels, lower RBC ATP, and NADPH/NADP ratio ( P < 0.0001). Multivariate analysis clearly differentiated control, sickle cell trait, and Hb-disordered groups based on metabolic profiles. CONCLUSIONS: Hemoglobinopathies show significant disruptions in glucose metabolism and redox equilibrium.