Case report: Immunoglobulin M-mediated, temperature-dependent neutrophil agglutination as a cause of pseudoneutropenia

The authors report the case of a 77-year-old man in whom intermittent neutropenia developed during a prolonged hospitalization. Laboratory records revealed wide variations in the patient's routine leukocyte counts, Examination of the peripheral smear revealed clumps of 2-3 polymorphonuclear leukocytes throughout the slide and large aggregates (>50 cells) along the smear edges. Neutrophil clumping also was observed in blood anticoagulated with citrate or heparin. Replacement of patient plasma with saline prevented agglutination. Addition of patient plasma or serum to normal cells induced neutrophil agglutination. Holding the patients blood at 37 degrees C prevented agglutination, which occurred spontaneously and more exuberantly as the temperature was reduced to 22 degrees C. Flow cytometry revealed immunoglobulin M on neutrophil surfaces. Spontaneous agglutination resolved 6 months after resection of the patient's subsequently diagnosed colon cancer. This is the first report of immunoglobulin M-induced neutrophil clumping occurring in the setting of malignancy, and the first reported immunoglobulin M not to require ethylenediaminetetraacetic acid as a cofactor for agglutination.