Cold-Agglutinin Hemolytic Anemia

Thanks to Dr. Hegarty for an excellent discussion on a case of a young woman presenting with subacute progressive B symptoms and acute jaundice found to have signs and symptoms of hemolytic anemia. Ultimately her Coombs DAT/C3 test returned positive for cold agglutinins. Luckily, her pneumonia tested positive for mycoplasma, thus reducing her risk of finding a concomitant malignancy that would otherwise be more likely if an infectious precipitant were not present. Some learning points from Dr. Hegarty:

Cold Agglutinin Hemolytic Anemia:

  • IgM antibody is formed that binds to antigens on RBC membrane
  • The antibodies are high avidity but low affinity, and better at lower temperatures (many variants with different thermal ranges).
  • Activates Classical Complement Pathway (C1, C2/C4, etc.)
  • Primarily extravascular hemolysis.
  • Associated with:
    • Mycoplasma pneumoniae infection*
    • EBV infection
    • CLL/SLL or other lymphoid malignancies
    • Others: CMV, legionella, citrobacter, flu, varicella, IgM MGUS, other cancers (adenocarcinoma).
  • Treatments:
    • Cold avoidance
    • Rituximab-containing regimens if severe/refractory (takes a while)
    • PLEX if hemolysis is severe/critically ill. (doesn’t last long)
    • Not much role for steroids (they help in warm AIHA though)
Agglutinated RBCs

Agglutinated RBCs