Relationship of glutathione levels and Heinz body formation to irreversibly sickled cells in sickle cell anemia.

To assess the possibility that the membrane lesion seen in sickle cells involves oxidant damage, we investigated the relationship between irreversibly sickled cells and glutathione levels and Heinz body production. We found that the mean level of red cell glutathione, whether expressed as micromoles per gram of hemoglobin or micromoles per milliliter of cell water, was significantly decreased in 39 patients with sickle cell anemia. A weak but significant negative correlation between glutathione levels and irreversibly sickled cell counts in the patients was observed. Stractan density gradient studies were performed to determine glutathione differences in normal- and abnormal-appearing sickle cells. The percent of abnormal cells in each of the five stractan gradient fractions was negatively correlated with both the micromole per gram of hemoglobin and micromole per milliliter of cell water levels of glutathione. Another indicator of susceptibility to oxidant stress, Heinz body formation, was increased in patients with sickle cell anemia vs controls in response to oxidant stress. Surprisingly, we found that the majority of Heinz bodies were in the non-ISC fraction of cells, rather than in the irreversibly sickled cells.