Undiagnosed Cold Agglutinin Disease Unmasked by Gram-Negative Sepsis

Cold agglutinin hemolytic anemia (CAHA) is a rare disorder characterized by autoantibody-mediated erythrocyte hemolysis. Cold agglutinin disease (CAD) is associated with a lymphoproliferative disorder, whereas cold agglutinin syndrome (CAS) is secondary to malignancy, autoimmune disease, or infection, particularly Mycoplasma pneumoniae or Epstein–Barr virus infections. We describe a unique case of CAHA in an older adult woman presenting in Escherichia coli septic shock, who was also found to have a small B-cell clone. We propose that our patient had subclinical undiagnosed CAD and that hemolysis was precipitated by gram-negative septic shock. Differentiating CAD from CAS is important for proper management.