Adult Patients with HbS-Only Phenotype of Sickle Cell Disease Have a Decreased Arginine/Asymmetric Dimethylarginine Ratio

Abstract

Introduction: Leg ulcer is the most common cutaneous manifestation of sickle cell disease (SCD). Asymmetric dimethylarginine (ADMA) inhibits nitric oxide synthase, reducing nitric oxide availability, and causing endothelial dysfunction. This study examined the relationship between arginine/ADMA ratio and leg ulcers in SCD. METHODS: This was a cross-sectional analytical study of 90 adult subjects including 30 "HbS only" with leg ulcer, 30 "HbS only" without leg ulcer and 30 HbAA subjects. Plasma arginine and ADMA levels were measured by ELISA method. RESULTS: Median arginine level, ADMA level, and arginine/ADMA ratio were 21.05 µmol/L, 3.0 µmol/L, and 7.41, respectively, for HbS-only with leg ulcer; 25.9 µmol/L, 2.8 µmol/L, and 9.6, respectively, for HbS-only without leg ulcer; and 47.8 µmol/L, 1.0 µmol/L (CI: 1.0-1.2), and 48.5, respectively, for HbAA subjects. Median plasma <sc>l</sc>-arginine level was significantly lower in HbS with leg ulcer compared to HbS without leg ulcer (p < 0.001) and HbAA subjects (p < 0.001). Conversely, median plasma ADMA level was significantly higher in HbS-only with leg ulcer compared to HbS without leg ulcer (p = 0.002), and HbAA subjects (p < 0.001). Median arginine/ADMA ratio was significantly lower in HbS-only patients with leg ulcer. CONCLUSION: The HbS-only patients with leg ulcers have lower arginine, higher ADMA, and lower arginine/ADMA ratio when compared to those without leg ulcers and HbAA controls. The prospective arginine/ADMA ratio should be studied to screen patients with higher risks of leg ulcers that could be prevented with specifically targeted care. .