Cold agglutinin hemolytic anemia in a patient with COVID-19 infection

<p style="font-weight: 400;"><strong>ABSTRACT </strong></p> <p style="font-weight: 400;"><strong>Background: </strong>Autoimmune hemolytic anemia (AIHA) is a rare but increasingly recognized complication of COVID-19. We present a unique case of severe cold AIHA (cAIHA) in the setting of concurrent COVID-19 infection that exhibited a relapsing course requiring rescue therapy.</p> <p style="font-weight: 400;"><strong>Case Presentation:</strong>  A 73-year-old male with chronic obstructive pulmonary disease who presented with worsening cough and dyspnea was found to have acute COVID-19 infection. Laboratory investigations revealed severe anemia, elevated lactate dehydrogenase (LDH), low haptoglobin, reticulocytosis, and positive direct antiglobulin test (DAT) with cold agglutinin titers, consistent with cAIHA. Extensive infectious, autoimmune, and malignancy workup was unremarkable. He was initially managed with corticosteroids, folic acid, and weekly rituximab. While symptoms improved temporarily, he experienced hemolytic relapse, necessitating rescue plasmapheresis and transfusion support. Hematologic parameters stabilized, and he was asymptomatic with no evidence of hemolysis at three-month follow-up.</p> <p style="font-weight: 400;"><strong>Conclusion:</strong> COVID-19 may trigger cold AIHA through immune dysregulation and complement activation. Diagnosing cAIHA in COVID-19 is complex due to overlapping features and high DAT positivity rates without active hemolysis. This case underscores the importance of individualized management, balancing immunosuppression and supportive care. Further research is needed to understand the pathogenesis and optimal treatment strategies for COVID-19-associated cAIHA.</p> <p style="font-weight: 400;"> </p>