Cold agglutinin disease (CAD) is a rare autoimmune haemolytic anaemia caused by cold-reactive antibodies that destroy red blood cells. Patients present with symptom-producing anaemia and debilitating cold-induced circulatory symptoms. First-line management targets both haematologic and symptom-related outcomes.
Evidence-based guidelines support a B-cell–depleting monoclonal antibody as the foundation of first-line therapy, which may be used as monotherapy or in combination with a cytotoxic agent. Structured supportive care — addressing environmental triggers and haematologic risks — is also a key component of management. The complete regimen, dosing schedule, and sequencing are available in the full protocol.