Cold Agglutinin Disease: Challenges in the Serological Workup and Management

Abstract Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia associated with autoantibodies that react mainly in the cold. CAD can interfere with immunohematology tests. We report two cases of CAD presented initially as blood grouping discrepancy leading us to further workup. Case I was a 61-year-old female with symptoms of weakness, bone pain, and difficulty breathing with laboratory findings of high cold agglutinin titers of 1:1024. Bone marrow aspirate revealed a mixture of >30% plasma cell and plasma blast. Bone marrow biopsy revealed an interstitial, focal, and nodular pattern of involvement by plasma cells, leading to the diagnosis of plasma cell dyscrasias. Case II analyzed was benign CAD with cold agglutinin titers of 1:64, with no other abnormality. Both patients were managed successfully. We report serological and clinical findings of two CAD cases with similar serological findings but different clinical outcomes.