Abstract / Summary
Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia caused by cold-reactive IgM autoantibodies that activate the classical complement pathway.It is characteristically associated with clonal B-cell lymphoproliferative disorders, and its association with myelodysplastic syndrome (MDS) is rare.We report a 75-year-old woman evaluated over nine months for isolated, predominantly indirect hyperbilirubinemia attributed to hepatobiliary disease before hemolysis was recognized.An anti-IgG-only direct antiglobulin test (DAT) was negative, and she was referred as having Coombs-negative hemolytic anemia; a complement-inclusive DAT subsequently demonstrated polyspecific antiglobulin and anti-C3b/C3d positivity at 3+ with negative anti-IgG, with cold agglutinin titers above 1:1024 and low C4, confirming complement-mediated hemolysis.Recurrent specimen interference, including prewarming requirements and spuriously elevated mean corpuscular hemoglobin concentration, had been present for months.Bone marrow evaluation demonstrated MDS with isolated del(5q) alongside a small IgM-kappa monoclonal protein; to our knowledge, this coexistence has not previously been reported, although the source of the cold agglutinin was not established.After deterioration to a hemoglobin nadir of 7.3 g/dL, she received two units of packed red blood cells and the complement C1s inhibitor sutimlimab.Hemoglobin entered the reference range by day 33 and remained stable through day 103 without further transfusion, with near-normalization of lactate dehydrogenase and substantial improvement in bilirubin.