In the direct antiglobulin test (DAT/Coombs), a positive result is obtained when anti-human globulin reagent causes agglutination of washed red cells. Which of the following clinical scenarios would most specifically give a positive DAT with polyspecific AHG, positive with anti-IgG, but NEGATIVE with anti-C3d?

• A Cold agglutinin disease with IgM antibodies activating complement
• B Warm autoimmune haemolytic anaemia due to IgG antibodies ✓
• C Drug-induced immune haemolysis via hapten mechanism (penicillin)
• D Haemolytic transfusion reaction with IgM isohemagglutinins

Explanation

Warm AIHA characteristically coats RBCs with IgG antibodies at 37°C without significant complement activation, yielding a DAT positive with anti-IgG but negative with anti-C3d. In contrast, cold agglutinin disease features IgM that activates complement, leaving only C3d on the cell surface after IgM elutes, so DAT is positive with anti-C3d but negative with anti-IgG. Penicillin hapten mechanism also deposits IgG but may be distinguished by drug withdrawal. IgM isohemagglutinins are efficient complement activators giving a C3d-positive pattern.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.