Hemolytic anemia in chronic large granular lymphocytic leukemia of natural killer cells: Cytotoxicity of natural killer cells against autologous red cells is associated with hemolysis

Background: It has been suggested that natural killer cells are effecters in some hemolytic transfusion reactions, but a direct mechanism of the destruction of red cells has not been demonstrated. Case Report: Lytic activity of natural killer cells against autologous red cells was found in a patient with large granular lymphocytic leukemia of natural killer cells and hemolytic anemia, with no evidence of immune antibody or complement-mediated hemolysis, Large granular lymphocytes in the blood showed a CD2(+) CD3(-) CD16(+) CD57(+) phenotype, cytotoxic activity against natural killer cell-sensitive K562 target cells, and no lytic activity against natural killer cell-resistant JY target cells, Cytotoxicity directed against red cells was quantified by a Cr-51-specific release assay with autologous and ABO-identical red cells used as target cells and the patient's purified natural killer cells used as effector cells in the presence and absence of autologous serum. The cytotoxic activity of natural killer cells was directed against autologous red cells but not against allogeneic red cells, and it was not enhanced by the presence of autologous serum in the medium. Clinical remission was induced by the administration of cyclophosphamide, after which no evidence of cytotoxic activity against the red cells could be found. Conclusion: Hemolytic anemia in the presence of a negative direct antiglobulin test can be attributed to a direct cytotoxic mechanism mediated by natural killer cells.