What is the role of complement levels 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 chronic cold agglutinin disease, complement tends to be depleted. Thus, the hemolysis is self-controlled, and anemia may be only mild or moderate, because these C3dg-coated RBCs are no longer capable of reacting with the IgM antibody in the cold, the C3dg-coated RBCs are not recognized by the macrophages, and low complement levels become rate limiting.

Temporary increases in complement levels, as can occur with intercurrent febrile illnesses, can increase hemolysis. Lytic components of complement C5-C9 generally do not form on these cells, and intravascular hemolysis by complement is less likely to occur. [15] Hemolysis develops acutely following M pneumoniae infections and lasts approximately 1-3 weeks. Subclinical mild hemolysis with reticulocytosis may also occur, and the results of a direct Coombs test may be weakly positive, especially with M pneumoniae infections.

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