What is the role of red blood cells (RBCs) in the pathophysiology of cold agglutinin disease?

Updated: Aug 28, 2018
  • Author: Salman Abdullah Aljubran, MD; Chief Editor: Michael A Kaliner, MD  more...
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In vivo, the IgM antibody attaches to RBCs and causes them to agglutinate at temperatures below 37°C and maximally at 0-5°C, resulting in impaired blood flow to the digits, nose, and ears (ie, areas more likely to have colder temperatures [in the 30°C range]) when exposed to the cold.

Fixation of the C3 component of complement to the RBC by the cold agglutinin usually occurs in vivo at higher temperatures than those required by the IgM cold agglutinin to attach to the RBC, but it is generally less than 31°C. When the IgM/C3b-coated RBC circulates to warmer tissues, the IgM dissociates, leaving complement C3b on the original RBC.

The dissociated IgM cold agglutinin can then bind to another RBC at lower temperatures. Fixation of complement results in C3b and/or C4b components on the RBC membrane, which may lead to phagocytosis by macrophages in the reticuloendothelial system, particularly in the liver, where the macrophages have specific complement receptors. With time, the C3b components are converted enzymatically to C3dg, which is not recognized by macrophage receptors.

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