Pseudoneutropenia Caused by Leukoagglutination in Cold Agglutinin Syndrome: A Case Report

A woman in her 70s with Child-Pugh C cirrhosis presented with fever and was found to have neutropenia, leading to treatment for presumed neutropenic fever despite negative cultures and rapid defervescence.Evaluation of discordant red-cell indices suggestive of spurious macrocytosis revealed marked discordance among red-cell indices, with hemoglobin disproportionately higher relative to the red-cell count and hematocrit, suggesting cold agglutination (Table 1).A repeat complete blood count was performed on a briefly prewarmed (37C) sample to minimize cold agglutinin-related artifacts.Repeat complete blood count analysis of a prewarmed sample corrected the red-cell indices and was accompanied by partial correction of the neutrophil count, establishing pseudoneutropenia (Table 1).A direct antiglobulin test was positive for C3d, and the cold agglutinin titer was 1:512.Peripheral-blood smear obtained at room temperature shows erythrocyte agglutination and clustering of neutrophils (Figure 1).The arrow indicates neutrophil aggregation (leukoagglutination), explaining the spuriously low automated neutrophil count.Cold agglutinin-mediated processes can cause a complement-mediated autoimmune hemolytic anemia characterized by IgM-mediated erythrocyte agglutination at low temperatures [1].Pseudoneutropenia due to in vitro leukocyte aggregation has been reported in association with cold agglutinins, EDTA-dependent antibodies, infections, and certain medications [2][3][4].Recognition of cold agglutinin-mediated leukoagglutination is essential to avoid misdiagnosis of neutropenic fever and unnecessary antimicrobial therapy.