Arginase-1 as a biomarker of hemolytic burden in sickle cell anemia and β-thalassemia: A comparative study with healthy controls

Objectives: Chronic hemolysis is a central feature of sickle cell anemia (SCA) and β-thalassemia and contributes to vascular dysfunction through disruption of arginine metabolism and nitric oxide homeostasis. Arginase-1 has emerged as a potential mediator of these processes; however, comparative evidence across major hemoglobinopathies remains limited. Methods: This analytical comparative case–control study included 135 adults: 45 patients with SCA, 45 patients with β-thalassemia, and 45 healthy controls. Serum Arginase-1 concentrations were measured by enzyme-linked immunosorbent assay and evaluated in relation to established hemolytic biomarkers. Group comparisons, correlation analyses, multivariable regression, and receiver operating characteristic (ROC) curve analyses were performed. Results: Serum Arginase-1 levels differed significantly among groups, increasing progressively from healthy controls (21.02 ng/mL) to β-thalassemia (39.54 ng/mL) and SCA (54.58 ng/mL) ( p = 2.84 × 10 -56 ). Arginase-1 correlated strongly with lactate dehydrogenase (r = 0.84), indirect bilirubin (r = 0.80), and reticulocyte percentage (r = 0.85) (all p < 0.001) but not with ferritin. Disease category was the strongest independent predictor of Arginase-1 levels in multivariable analysis (R 2 = 0.822; adjusted R 2 = 0.814). ROC analysis demonstrated strong discriminatory ability within the study cohort (area under the curve = 0.9936; 95% confidence interval: 0.9801–1.0000), with an observed sensitivity of 96.67% and specificity of 100.00% at a study-derived cutoff of 32.90 ng/mL. Conclusion: Arginase-1 is markedly elevated in SCA and β-thalassemia and closely reflects hemolytic burden. The observed discriminatory performance within this study cohort suggests that Arginase-1 may have potential utility as a biomarker of hemolysis; however, these findings require external validation in independent populations before any clinical application can be considered.