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

Betty S. Pace, Archil Shartava, Ardie Pack-Mabien, Mudhari Mulekar, Alfredo Ardia, Steven R. Goodman

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)26-32
Number of pages7
JournalAmerican Journal of Hematology
Issue number1
StatePublished - May 1 2003
Externally publishedYes


  • Dense cells
  • Glutathione
  • N-acetylcysteine
  • Sickle cell disease
  • Vaso-occlusive episodes

ASJC Scopus subject areas

  • Hematology


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