Neutrophil-to-Lymphocyte Ratio in Pediatric Sickle Cell Anemia: A Case-Control Study from Gezira State, Sudan

Abstract

Background: Sickle Cell Anemia (SCA) is a common hereditary hemoglobinopathy marked by chronic intravascular hemolysis, recurrent microvascular occlusion, and sustained systemic inflammation.
Objective: This study evaluated the clinical utility of the Neutrophil-to-Lymphocyte Ratio (NLR) as an accessible inflammatory biomarker among pediatric SCA patients in Sudan and examined its relationships with disease manifestations, clinical crisis phenotypes, and therapeutic regimens.
Methods: A hospital-based case-control investigation was conducted at Wad Medani Pediatric Teaching Hospital in Gezira State, Sudan, enrolling 130 pediatric participants (80 confirmed SCA cases and 50 healthy controls). A formal sample size calculation was performed to ensure statistical power (>80%). Automated complete blood counts were performed using a Sysmex XP-300 hematology analyzer to calculate absolute NLR values. Statistical comparisons, ROC diagnostic evaluations, and stratified subgroup analyses were performed using SPSS version 22.
Results: Pediatric SCA patients exhibited significantly elevated mean NLR compared with healthy controls (3.89 ± 2.60 vs. 1.56 ± 0.29, p < 0.001). Receiver Operating Characteristic (ROC) analysis revealed robust diagnostic discrimination (AUC = 0.79, 95% CI: 0.71–0.87), yielding 63.8% sensitivity and 98.0% specificity at an optimal cutoff of >2.2. NLR levels varied markedly by clinical crisis category (p = 0.001), peaking during hand-foot syndrome (6.84 ± 1.66) and acute infection (5.00 ± 3.06). However, subgroup comparisons involving rare complications (such as acute chest syndrome, n=2, and cerebrovascular accident, n=2) require cautious interpretation due to limited subgroup sample sizes. Hydroxyurea therapy was associated with a substantial reduction in mean NLR (1.48 ± 0.33 vs. 4.44 ± 2.57 in non-treated cases, p = 0.001). Conversely, NLR exhibited no significant correlation with patient age, sex, underlying anemia severity, or routine folic acid supplementation.
Conclusion: NLR represents a cost-effective, readily available leukocytic biomarker that effectively reflects systemic inflammatory activity during acute vaso-occlusive crises and demonstrates favorable pharmacological response to hydroxyurea in pediatric SCA. While limited subgroup sizes warrant larger prospective validation, serial NLR monitoring offers clinical utility in resource-constrained settings.