When Jaundice Isn’t Just the Liver’s Fault: A Chilly Case of Cold Autoimmune Hemolytic Anemia
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Publication Date
4-29-2026
Keywords
oregon, psvmc, psvmc gme, psvmc oaa
Disciplines
Medical Education
Abstract
Introduction: Cold agglutinin disease (CAD), a subtype of autoimmune hemolytic anemia (AIHA), is characterized by IgM autoantibodies that target red blood cell antigens at low temperatures, leading to agglutination in cooler peripheral tissues and hemolysis. Predominately directed against the “I” or “i” antigens, cold agglutinins are commonly associated with Mycoplasma pneumoniae and infectious mononucleosis. Distinguishing warm AIHA from CAD can be challenging. Definitive diagnosis relies on antibody testing, with warm AIHA primarily involving IgG and CAD involving IgM. We report a case of CAD initially misattributed to drug-induced liver injury in the setting of a viral upper respiratory infection. Case Presentation: A 39-year-old woman with no significant past medical history presented with acute weakness and fevers. Symptoms were initially attributed to a viral illness and self-treated with Acetaminophen and Ibuprofen, achieving only partial relief. She visited her primary care provider the day prior to admission with new onset dark urine and jaundice. Concern for acute hepatitis prompted referral to the emergency department (ED). Initial evaluation revealed marked hyperbilirubinemia, elevated transaminases, and an echogenic liver on ultrasound, suggestive of fatty infiltration or chronic hepatocellular disease. She was admitted with presumed acetaminophen-induced acute hepatitis. Concurrently, a 4.6 g/dL drop in hemoglobin and positive antibody screen (Direct antiglobulin testing (DAT) positive for both IgG and C3), led to presumptive diagnosis of warm AIHA. Further workup revealed Epstein-Barr virus infection, confirming CAD. She was managed with supportive measures, counseled on avoidance of cold exposure, and discharged with close hematology follow-up. Discussion: CAD accounts for 20–25% of AIHA cases and may present insidiously or acutely in association with infections. Primary management includes avoidance of cold exposure, warming of intravenous fluids and transfusions, and treatment of underlying triggers. In severe cases, plasmapheresis may provide temporary benefit, and Rituximab-containing regimens are considered for primary CAD. This case highlights how initial anchoring to a presumed diagnosis of acute hepatitis delayed recognition of hemolysis. Cognitive biases—including premature closure, authority bias, framing bias, and availability bias—contributed to the initial misdiagnosis. Detailed history, attention to evolving data, and re-evaluation of the working diagnosis were essential in identifying CAD and implementing appropriate management.
Specialty/Research Institute
Graduate Medical Education
Specialty/Research Institute
Internal Medicine
