ISSN 2997-1036
International Journal of Hematology | Vol. 10, No. 6, June 2019 | pp. 41–48
DOI: 10.46882/2019/IJH/000114
Original Article
Title: Impact of systemic hydroxyurea on plasma asymmetric dimethylarginine concentrations and macrovascular stress 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: Endothelial cell nitric oxide synthase inhibition by elevated asymmetric dimethylarginine (ADMA) drives severe pulmonary vascular remodeling in sickle cell disease. This prospective cohort study evaluated the long-term impact of optimized hydroxyurea therapy on plasma asymmetric dimethylarginine concentrations and pulmonary hypertension risk metrics in 50 adult patients with steady-state sickle cell anemia (HbSS). Hydroxyurea was titrated up to the maximum tolerated dose (15 to 25 mg/kg/day) over 12 months, with tricuspid regurgitant jet velocity (TRJV) monitored via Doppler echocardiography. Baseline mean asymmetric dimethylarginine levels fell significantly from 1.84 ± 0.32 μmol/L to 0.92 ± 0.15 μmol/L at month 12 (P < 0.001). Concurrently, the proportion of patients presenting with high-risk tricuspid velocities (TRJV ≥ 2.5 m/s) dropped from 36.0% to 14.0%. Reductions in asymmetric dimethylarginine levels correlated positively with fetal hemoglobin increases (r = 0.54, P < 0.01) and drops in absolute reticulocyte counts. These findings confirm that hydroxyurea successfully mitigates competitive inhibitors of nitric oxide synthesis, providing an accessible pharmacological pathway for reducing chronic macrovascular endothelial stress in adult sickle cell variants.
Keywords: Sickle cell anemia, hydroxyurea, asymmetric dimethylarginine, tricuspid regurgitant jet velocity, endothelial dysfunction
Manuscript Timeline: Received: March 15, 2019; Revised: April 24, 2019; Accepted: May 12, 2019; Published: June 19, 2019