Cold agglutinin disease can be a complication of infection with which organism?

• A. Staphylococcus aureus
• B. Streptococcus pneumoniae
• C. Mycoplasma pneumoniae
• D. Escherichia coli

Answer: (C)

Cold agglutinin disease is an autoimmune form of hemolytic anemia caused by IgM antibodies that react with red blood cells in the cold and activate complement, leading to hemolysis. Infections can trigger the production of these cold-reactive antibodies, with Mycoplasma pneumoniae being the most classic association. The antibodies often target the I antigen on red cells, causing agglutination in cooler parts of the body and resulting in hemolysis that is complement-mediated. Clinically you may see acrocyanosis or Raynaud-like symptoms in cold exposure, and labs typically show a positive direct antiglobulin test with C3d (often without IgG). The other organisms listed aren’t classically linked to this antibody-mediated hemolysis pattern.