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.
Copyright 2003 Wiley-Liss, Inc.