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Cold Antibodies

Some important aspects of cold antibodies are:

  • Most are IgM and are not clinically significant
  • May interfere with detection of clinically significant antibodies if they react at AHG phase.
  • Screen cells and panel cells will have positive reactions in IS phase and strength will diminish or antibody will not be detected at AHG phase.
  • Auto control will be positive if the cold antibody is an autoantibody.

Binding of antibody to antigen occurs at room or colder temperatures and may start to disassociate from the red cell membrane at warmer temperatures. Reactions will appear weaker or be negative at warmer temperatures. (Example: 4+ at IS phase and W (weak)+ at AHG phase.)


If a nonspecific cold antibody or cold agglutinin is suspected, warm the sample and testing reagents, including saline, to 37° C. Only do reaction readings at AHG; bypassing the optimum reaction temperature prevents activation and binding of the cold antibody .