Effects of N-acetylcysteine on dense cell formation in sickle cell disease

Am J Hematol. 2003 May;73(1):26-32. doi: 10.1002/ajh.10321.


The extent to which dense and irreversible sickle cells (ISCs) contribute to vaso-occlusive episodes in sickle cell disease remains unclear. N-Acetylcysteine (NAC) inhibits dense cell and ISC formation in sickle erythrocytes in vitro and restores glutathione levels toward normal. A phase II double-blind randomized clinical trial was completed to determine the efficacy of NAC in decreasing dense cell and ISC formation, and vaso-occlusive episodes in sickle cell disease. Twenty-one subjects with a history of at least two vaso-occlusive episodes per year and 6% dense cells were enrolled. Four treatment groups were analyzed; NAC at a dose of 2,400 mg per day decreased the percent dense cells from 20.1 +/- 2.9 to 12.6 +/- 2.1 (P < 0.05) and increased red cell glutathione levels from 292.8 +/- 74.5 to 576.7 +/- 155.1 (P < 0.05). In addition, we observed a decrease in vaso-occlusive episodes from 0.03 to 0.006 episodes per person-days and a decreased in relative risk to R = 0.39. Although NAC did not significantly decrease the number of ISCs, there was a downward trend at all doses tested. In summary, NAC inhibited dense cell formation, restored glutathione levels toward normal, and decreased vaso-occlusive episodes at a well-tolerated dose of 2,400 mg per day. To determine the long-term efficacy and safety of NAC, a multicenter phase III clinical trial is required.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcysteine / blood
  • Acetylcysteine / therapeutic use*
  • Adolescent
  • Adult
  • Anemia, Sickle Cell / blood*
  • Anemia, Sickle Cell / complications
  • Anemia, Sickle Cell / drug therapy*
  • Double-Blind Method
  • Erythrocytes, Abnormal / chemistry
  • Erythrocytes, Abnormal / pathology*
  • Female
  • Glutathione / blood
  • Humans
  • Male
  • Placebos
  • Vascular Diseases / etiology
  • Vascular Diseases / prevention & control


  • Placebos
  • Glutathione
  • Acetylcysteine