Drug-associated "bite cell" hemolytic anemia.

ABSTRACT

PURPOSE: "Bite cell" hemolytic anemia is a variant of drug-related hemolysis usually associated with methemoglobinemia and Heinz body inclusions in red blood cells secondary to oxidant drug injury. Bite cells are morphologically characterized as poikilocytes with one or more semicircular portions removed from the cell margin. The purpose of this report is to emphasize the importance of peripheral smear examination in patients with possible drug-associated hemolytic anemia. The morphologic characteristics of bite cells by light microscopy and scanning electron microscopy are detailed in this study, and the pathophysiologic mechanism is discussed. PATIENTS AND METHODS: Clinical and laboratory data were retrospectively studied on eight patients (two men and six women, aged 29 to 85 years) who showed evidence of bite cell hemolytic anemia associated with drug exposure. Multiple standard hematologic laboratory evaluations for hemolytic anemia were performed. Five hundred red blood cells were counted from randomly selected peripheral smear fields for the calculation of bite cell percentage. RESULTS: Peripheral smears showed predominantly normochromic normocytic red cells with prominent bite cells and occasional blister cells. Bite cell counts ranged from 5.5% to 13.6% (mean, 8.7 +/- 3.0% SD) associated with a hematocrit reduction of 3.0% to 13.2% (mean, 8.5 +/- 3.8% SD) and concomitant reticulocytosis of varying degree from 2.3% to 15.4% (mean, 7.3 +/- 4.9% SD). Withdrawal of the offending drug(s) and treatment of underlying diseases resulted in improvement of hemolytic anemia and eventual disappearance of bite cells. A close correlation between hematocrit reduction, reticulocyte response, and bite cell percentage increase was seen. The usual biochemical markers of hemolysis were not consistently observed. Scanning electron microscopy confirmed the light microscopic evidence of bite cell morphology and revealed a keratocytic variant. CONCLUSION: This study emphasizes the importance of peripheral smear examination for early diagnosis and management of bite cell hemolytic anemia. Withdrawal of the putative offending drug(s) and treatment of underlying disorders should result in improvement of this form of drug-associated hemolysis.