ISSN 2997-1036
International Journal of Hematology | Vol. 9, No. 8, August 2018 | pp. 57–64
DOI: 10.46882/2018/IJH/000104
Original Article
Title: Impact of systemic hydroxyurea on nitric oxide metabolite concentrations and endothelial activation indices in adult sickle cell anemia
Names of Authors: S. T. Adeyemi¹, U. V. Okoye², W. X. Salami³
Authors’ Affiliations: ¹Department of Haematology and Blood Transfusion, Obafemi Awolowo University, Ile-Ife, Nigeria; ²Department of Medicine, University of Nigeria Teaching Hospital, Enugu, Nigeria; ³Department of Paediatrics, Ahmadu Bello University, Zaria, Nigeria
Abstract: Severe reduction in nitric oxide availability driven by cell-free hemoglobin consumption causes widespread vasoconstriction and endothelial stress in sickle cell anemia. This prospective cohort study evaluated the long-term impact of optimized hydroxyurea therapy on plasma nitric oxide metabolites (NOx) and soluble vascular cell adhesion molecule-1 (sVCAM-1) concentrations in 50 adult patients with stable sickle cell anemia (HbSS). Hydroxyurea was administered at 15 to 20 mg/kg/day and monitored over 12 months. Plasma markers were quantified via colorimetric and enzyme-linked immunosorbent assays at baseline, 6 months, and 12 months. Baseline mean nitric oxide metabolite concentration rose significantly from 14.2 ± 3.8 μmol/L to 38.6 ± 6.2 μmol/L at month 12 (P < 0.001). Concurrently, plasma sVCAM-1 levels decreased by 42.1%, falling from a mean baseline of 1,240 ng/ml to 718 ng/ml. This endothelial improvement correlated positively with an increase in fetal hemoglobin from 5.2% to 15.6% and a drop in serum lactate dehydrogenase. These chemical kinetics demonstrate that hydroxyurea acts as a direct nitric oxide donor alongside its fetal hemoglobin-inducing properties, successfully reducing endothelial activation and microvascular stress indices in adult sickle cell cohorts.
Keywords: Sickle cell anemia, hydroxyurea, nitric oxide, cell adhesion molecules, endothelial activation
Manuscript Timeline: Received: May 05, 2018; Revised: June 15, 2018; Accepted: July 09, 2018; Published: August 14, 2018