In autoimmune haemolytic anaemia (AIHA), warm AIHA is caused by IgG antibodies reactive at 37°C, primarily cleared by splenic macrophages. Cold AIHA (cold agglutinin disease) is caused by IgM antibodies active at 4°C. Which test distinguishes warm from cold AIHA on direct antiglobulin test (DAT)?

• A Warm AIHA: DAT positive with anti-C3d only; Cold AIHA: DAT positive with anti-IgG
• B Both show identical DAT patterns with anti-IgG positivity
• C Warm AIHA: DAT positive with anti-IgG; Cold AIHA: DAT positive with anti-C3d ✓
• D Warm AIHA: DAT negative; Cold AIHA: DAT positive with anti-IgM

Explanation

In warm AIHA, IgG antibodies coat red cells and DAT detects IgG (anti-IgG positive, ± C3d). In cold agglutinin disease, IgM antibodies bind RBCs at 4°C, activate complement to C3b/C3d, then IgM dissociates at 37°C, leaving C3d on the cell surface. DAT therefore shows positive anti-C3d only, with no IgG detected. This DAT pattern differentiates the two: anti-IgG alone or anti-IgG+C3d favours warm; anti-C3d alone favours cold. DAT does not detect IgM directly because IgM falls off at body temperature.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.