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Case Report
Abstract
Introduction: Cold autoimmune hemolytic anemia (AIHA) is an uncommon, complement-mediated hemolysis typically driven by IgM autoantibodies; secondary forms are often infection-related. Severe, transfusion-refractory presentations are rare in older adults. We present an elderly patient with Mycoplasma pneumoniae and Epstein–Barr virus co-infection complicated by life-threatening cold agglutinin hemolysis.
Case report: Upon admission, a 79-year-old male patient presented with a one-week history of fatigue, pyrexia, nasal congestion, and dyspnea; examination findings revealed pallor, bibasilar crackles, and mild splenomegaly. Laboratory investigations indicated the presence of severe hemolytic anemia accompanied by compensatory reticulocytosis and thrombocytosis (hemoglobin 5.5 g/dL, hematocrit 17.2%, MCV 100 fL, reticulocytes 4.3%, platelets 514×10³/µL), elevated lactate dehydrogenase (LDH), and undetectable haptoglobin levels. The direct antiglobulin test yielded results of C3 positivity and IgG negativity, alongside an elevated cold-agglutinin titer; peripheral blood smear analysis revealed macrocytosis and red blood cell agglutination, with the presence of mature leukocytosis and an absence of blasts or dysplastic features. Abdominal computed tomography (CT) confirmed the presence of splenomegaly, while chest CT imaging revealed right lower lobe pneumonia characterized by bronchial wall thickening and diffuse bilateral reticulonodular opacities. Infectious disease testing returned positive results for Mycoplasma IgM and Epstein-Barr virus (EBV) capsid/nuclear antibodies, indicative of either a recent or reactivated infection. Notwithstanding two packed red blood cell (PRBC) transfusions, hemoglobin levels subsequently declined within a 12-hour period, necessitating the initiation of targeted therapy for cold agglutinin hemolysis, which included environmental warming, transfusions administered at elevated temperatures only as clinically warranted, intravenous fluids, methylprednisolone, and azithromycin; gastrointestinal bleeding was ruled out through endoscopic procedures, including both esophagogastroduodenoscopy and colonoscopy. Following these interventions, hemoglobin levels stabilized to 9.5 g/dL, with clinical symptoms showing marked improvement, allowing for discharge with a recommendation for close follow-up. The clinical presentation, characterized by DAT C3 positivity, red blood cell agglutination, pneumonia attributed to Mycoplasma, and positive EBV serologies, provides substantial evidence supporting the diagnosis of secondary cold agglutinin hemolysis resulting from infection-driven polyclonal IgM antibodies targeting I/i antigens with subsequent complement activation; the observed splenomegaly likely indicated an increase in extravascular clearance mechanisms. While primary cold agglutinin disease frequently exhibits a poor response to corticosteroid therapy, this secondary manifestation demonstrated improvement following infection-targeted treatment strategies and supportive transfusion practices mindful of temperature considerations.
Conclusions: In older adults with acute anemia and pneumonia, clinicians should maintain high suspicion for cold AIHA, especially with RBC agglutination and DAT C3-positivity. Rapid institution of warming measures, cautious use of warmed transfusions, treatment of precipitating infections, and early immunosuppression can reverse otherwise refractory hemolysis. This case underscores the potential severity of infection-triggered cold AIHA in the elderly, the importance of early recognition and temperature-aware transfusion practices, and the selective role of corticosteroids in secondary cold agglutinin hemolysis.
Recommended Citation
Calderon, Aura MC; Loayza, Jose; Salcedo, Luis; Mogollon, Ivan; and Asatrian, Asmik, "Severe Cold Agglutinin Hemolytic Anemia Secondary to Mycoplasma pneumoniae and Epstein-Barr Virus Co-infection in an Elderly Patient" (2026). Research Symposium. 7.
https://scholarworks.utrgv.edu/somrs/2026/posters/7
Included in
Severe Cold Agglutinin Hemolytic Anemia Secondary to Mycoplasma pneumoniae and Epstein-Barr Virus Co-infection in an Elderly Patient
Introduction: Cold autoimmune hemolytic anemia (AIHA) is an uncommon, complement-mediated hemolysis typically driven by IgM autoantibodies; secondary forms are often infection-related. Severe, transfusion-refractory presentations are rare in older adults. We present an elderly patient with Mycoplasma pneumoniae and Epstein–Barr virus co-infection complicated by life-threatening cold agglutinin hemolysis.
Case report: Upon admission, a 79-year-old male patient presented with a one-week history of fatigue, pyrexia, nasal congestion, and dyspnea; examination findings revealed pallor, bibasilar crackles, and mild splenomegaly. Laboratory investigations indicated the presence of severe hemolytic anemia accompanied by compensatory reticulocytosis and thrombocytosis (hemoglobin 5.5 g/dL, hematocrit 17.2%, MCV 100 fL, reticulocytes 4.3%, platelets 514×10³/µL), elevated lactate dehydrogenase (LDH), and undetectable haptoglobin levels. The direct antiglobulin test yielded results of C3 positivity and IgG negativity, alongside an elevated cold-agglutinin titer; peripheral blood smear analysis revealed macrocytosis and red blood cell agglutination, with the presence of mature leukocytosis and an absence of blasts or dysplastic features. Abdominal computed tomography (CT) confirmed the presence of splenomegaly, while chest CT imaging revealed right lower lobe pneumonia characterized by bronchial wall thickening and diffuse bilateral reticulonodular opacities. Infectious disease testing returned positive results for Mycoplasma IgM and Epstein-Barr virus (EBV) capsid/nuclear antibodies, indicative of either a recent or reactivated infection. Notwithstanding two packed red blood cell (PRBC) transfusions, hemoglobin levels subsequently declined within a 12-hour period, necessitating the initiation of targeted therapy for cold agglutinin hemolysis, which included environmental warming, transfusions administered at elevated temperatures only as clinically warranted, intravenous fluids, methylprednisolone, and azithromycin; gastrointestinal bleeding was ruled out through endoscopic procedures, including both esophagogastroduodenoscopy and colonoscopy. Following these interventions, hemoglobin levels stabilized to 9.5 g/dL, with clinical symptoms showing marked improvement, allowing for discharge with a recommendation for close follow-up. The clinical presentation, characterized by DAT C3 positivity, red blood cell agglutination, pneumonia attributed to Mycoplasma, and positive EBV serologies, provides substantial evidence supporting the diagnosis of secondary cold agglutinin hemolysis resulting from infection-driven polyclonal IgM antibodies targeting I/i antigens with subsequent complement activation; the observed splenomegaly likely indicated an increase in extravascular clearance mechanisms. While primary cold agglutinin disease frequently exhibits a poor response to corticosteroid therapy, this secondary manifestation demonstrated improvement following infection-targeted treatment strategies and supportive transfusion practices mindful of temperature considerations.
Conclusions: In older adults with acute anemia and pneumonia, clinicians should maintain high suspicion for cold AIHA, especially with RBC agglutination and DAT C3-positivity. Rapid institution of warming measures, cautious use of warmed transfusions, treatment of precipitating infections, and early immunosuppression can reverse otherwise refractory hemolysis. This case underscores the potential severity of infection-triggered cold AIHA in the elderly, the importance of early recognition and temperature-aware transfusion practices, and the selective role of corticosteroids in secondary cold agglutinin hemolysis.
