Evaluation of the level of endothelin-1 and tumor necrosis factor-alpha in patients with sickle cell disease

BACKGROUND: Sickle cell disorder (SCD) is a chronic hereditary hemoglobinopathy characterized by recurrent vaso-occlusive crises (VOCs), chronic inflammation, and endothelial dysfunction. Endothelin-1 (ET-1) and tumor necrosis factor-alpha (TNF-α) are key mediators implicated in vascular constriction, inflammation, and pain, and may serve as biomarkers reflecting disease activity and clinical status in pediatric SCD patients. OBJECTIVE: To evaluate TNF-α and ET-1 levels in patients with SCD and assess their correlation with clinical and hematological parameters. MATERIALS AND METHODS: This cross-sectional study was conducted at Basra Center of Hereditary Blood Diseases, Iraq, between February and August 2025. Sixty-four children aged 3–12 years with confirmed SCD (34 during crises and 30 in steady state) and 24 age- and sex-matched healthy controls were enrolled. Complete blood count parameters were assessed, and serum ET-1 and TNF-α levels were measured using sandwich enzyme-linked immunosorbent assay techniques. Statistical analyses included group comparisons and correlation testing between biomarkers and hematological indices. RESULTS: Serum ET-1 and TNF-α levels were significantly elevated in SCD patients compared with controls, especially during VOC ( P < 0.0001). ET-1 and TNF-α showed significant positive correlations with hematocrit, reticulocyte count, white blood cell count, and platelet count during crises. In the steady state, correlations with hematological parameters were weak. Hemoglobin (Hb) SS genotype patients exhibited higher ET-1 and TNF-α levels than HbSβ patients, particularly during crises. CONCLUSIONS: Children with SCD demonstrate marked elevations of ET-1 and TNF-α, especially during VOC, with higher levels in HbSS patients.