Pathogenesis and Clinical Features of Cold Agglutinin Disease

• Cold Agglutinin Disease (CAD, a type of Autoimmune Hemolytic Anemia, AIHA) is a rare disease, challenging at presentation and can present acutely or with more chronic symptoms
• CAD is a subtype of AIHA (accounting for ~20% of all AIHA) caused by IgM autoantibodies, which tend to react at cold temperatures; Cold Agglutinin Syndrome (CAS) is also an AIHA mediated by IgM, associated with systemic disease, most commonly infection or malignancy
• Hemolysis in CAD is complement-dependent with mainly extravascular hemolysis, typically in the liver
• CAD affects ~one person per million every year; middle-aged and elderly people, 40–80 years of age with average age of onset 60 years of age; more common in women than men