Leach et al reviewed the features distinguishing a clinically significant cold agglutinin from one that is primarily a laboratory phenomenon.
Clinically significant cold agglutinins may be identified in patients with:
(1) cold agglutinin disease
(2) lymphoproliferative disorders
(3) mycoplasma pneumonia
Finding
Insignificant
Significant
in vivo hemolysis
absent
present
bind complement
no
yes
agglutination
reversible
irreversible
thermal range
narrow (0 to 6°C)
wide (4 to 32°C)
maximum activity at 0 to 4°C
yes
no
active at room temperature (20°C) in saline
no
yes
agglutination at 30°C after incubation with albumin
not enhanced
enhanced
Significant cold agglutinins are usually IgM, while insignificant ones are usually not.
The Donath-Landsteiner antibody is a clinically significant cold agglutinin with features that differ in some of the features listed in the table above.
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