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Effect of Hydroxyurea Therapy on Markers of Inflammation and Clinical Variability Of Sickle Cell Anaemia; A Prospective Study at a Missionary Hospital
Abstract
Background: Immune mediators of inflammation are implicated in the pathophysiological processes and clinical variability of sickle cell anaemia (SCA). This study determined the effect of hydroxyurea therapy on markers of inflammation and clinical variability of sickle cell anaemia in Ghana.
Methods: This prospective case-control study was conducted at Methodist Hospital, Wenchi. Ninety participants (60 SCA patients and 30 apparently healthy controls (HbA)) aged 2-40 were recruited from March to July 2023. About 4 mL of blood was collected for complete blood count analysis using a Sysmex XN-550 haematology analyzer and serum C-reactive protein (CRP), interleukin (IL-6), and hepcidin using an enzyme-linked immunosorbent assay. Data were analyzed using SPSS version 27.
Results: Serum levels of IL-6 [4.7 (3.9-5.1) vs 3.0 (2.2-4.0), p<0.001], CRP [452.4±154.6 vs 267.5±84.2, p<0.001], NLR [1.4 (1.1-2.2) vs 0.9 (0.5-1.3), p<0.001], platelets [357.0 (248.5-445.5) vs 240.5 (180.5-264.5), p<0.001] and TWBC [10.3 (8.3- 12.6) vs 5.2 (4.3-5.9), p<0.001] were significantly elevated with reduction in levels of hepcidin [145.3 (109.2-185.2) vs 208.6 (150.6-246.4), p<0.001], HB [8.4±1.8 vs 12.8±1.3, p<0.001], RBC [2.6 (2.3-3.4) vs 4.5 (4.1-4.9), p<0.001] and HCT [25.6±5.4 vs 39.9±4.5, p<0.001] among SCA participants compared to the control group. However, the levels of the inflammatory markers showed significant reduction with improved haemogram in SCA participants treated with HU compared to the naïve group; [IL-6 (p=0.014), CRP (p<0.001), NLR (p=0.009), PLR (p=0.003), HB (p<0001), RBC (p=0.001), HCT (p=0.031), platelets (p<0.001), TWBC (p<0.001)]. Levels of IL-6 (rho=0.503, p<0.001), CRP (rho=0.449, p<0.001) platelets (rho=0.554, p<0.001) and TWBC (rho=0.300, p=0.020) positively correlated with disease severity. NLR, PLR and hepcidin levels showed no significant correlation with disease severity score (p>0.05).
Conclusion: In summary, hydroxyurea therapy significantly improves red cell indices and reduces inflammatory biomarkers, which minimizes the severity of sickle cell anaemia complications.