Evaluation of hydroxyurea effect in patients with sickle cell disease: A prospective observational study

Sickle cell disease (SCD) is characterized by chronic hemolysis, inflammation, oxidative stress, and recurrent vaso-occlusive complications leading to significant morbidity. Hydroxyurea (HU), a widely used disease-modifying therapy, increases fetal hemoglobin (HbF) and reduces clinical complications. Emerging evidence suggests additional anti-inflammatory and antioxidant effects. The objectives of this study were to compare the inflammatory markers, oxidative stress markers, hematological parameters, and quality of life from baseline to 6 months after HU therapy among patients with SCD.

In this prospective observational study, 16 HU-naïve patients with SCD were evaluated at baseline and after 6 months of HU therapy. Investigations included inflammatory markers (interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-α]), oxidative stress markers (malondialdehyde [MDA] and glutathione [GSH]), hematological parameters (HbF, sickle hemoglobin [HbS], leukocyte count, and neutrophil-to-lymphocyte ratio [NLR]), and quality of life assessed using the 36-Item Short Form Health Survey questionnaire.

Significant reductions in inflammatory markers were observed, with TNF-α decreasing from 5.82 ± 2.82 pg/mL to 4.64 ± 2.65 pg/mL (P = 0.006) and median IL-6 levels decreasing from 6.32 to 4.42 pg/mL (P = 0.001). Oxidative stress improved, with reduced MDA levels (P = 0.011) and increased GSH levels (P = 0.001). Hematological parameters showed significant improvement, including increased HbF and reductions in HbS, leukocyte count, and NLR (P < 0.001). HU therapy was well tolerated, with good compliance, improved quality of life, and a low incidence of complications.

HU may exert therapeutic benefit not only by increasing HbF but also through anti-inflammatory and antioxidant effects, leading to improved hematological stability and fewer complications in SCD.