Probable Cold Agglutinin Disease Presenting With Profound Anemia and Cardiopulmonary Decompensation in a 93-Year-Old...

Cold agglutinin disease (CAD) is an uncommon, complement-mediated autoimmune hemolytic anemia that predominantly affects older adults. We report a 93-year-old woman with ischemic heart disease, persistent atrial fibrillation treated with rivaroxaban, major valvular disease, and limited mobility who presented with progressive leg edema, dyspnea, chest pain, fatigue, and profound normocytic anemia. Her hemoglobin was 5.1 g/dL, compared with 9.7 g/dL approximately four months earlier. The initial evaluation focused on possible occult bleeding and cardiac decompensation. By the second day of the acute-care episode, the finalized blood-group confirmation result returned from the regional blood center reportedly noted cold-reactive antibodies, providing an early clue to cold-antibody-mediated hemolysis and redirecting the diagnostic work-up. No overt bleeding was identified, although gastrointestinal assessment remained incomplete. Subsequent hemolysis testing showed a lactate dehydrogenase level of 401 U/L, reticulocytes of 4.78%, and a positive direct antiglobulin test with C3d reactivity. Serum immunofixation identified an immunoglobulin M kappa monoclonal protein. Directed questioning then elicited long-standing cold intolerance, severe pain after cold food or beverages, and cold-triggered limb pain. Because the cold agglutinin titer and thermal amplitude were unavailable, the findings were considered strongly supportive of probable CAD associated with an immunoglobulin M-related clonal process rather than proof of a fully characterized hematologic disorder. Evaluation for an underlying cause was limited by the absence of on-site hematology services, and lymphoma or another marrow-based neoplasm could not be excluded. One packed red-cell unit was completed in the emergency department; a second was stopped when dyspnea developed against a background of marked edema and cardiac disease, and two further units were later given under diuretic cover. With transfusion support, diuresis, cold avoidance, and other supportive care, hemoglobin increased to 9.3 g/dL and cardiopulmonary symptoms improved. By discharge, she was alert and oriented to self and her surroundings and could ambulate with assistance or a walker. At approximately 12 weeks after discharge, she remained clinically stable. After discussion of the expected benefits and burdens, the patient, supported by her family, chose not to pursue invasive hematologic evaluation because its results were unlikely to alter the planned conservative management. This case emphasizes directed inquiry about temperature-related symptoms and careful calibration of diagnostic certainty when formal CAD testing is incomplete.