What is the role of infectious agents 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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The hemolytic anemia associated with monoclonal cold agglutinins is typically more serious than that associated with polyclonal cold agglutinins. The monoclonal form is usually chronic, whereas the polyclonal form is often limited. [24]

Some polyclonal IgM cold agglutinins arise in association with infections with Mycoplasma pneumoniae, infectious mononucleosis, influenza B, and human immunodeficiency virus (HIV), as well as with other infections. (Cold agglutinins develop in more than 60% of patients with infectious mononucleosis, but hemolytic anemia is rare.)

Cytomegalovirus (CMV), rubella virus, varicella-zoster virus (VZV), parvovirus B19, and Chlamydia psittaci have also been implicated. [25]

In the case of infectious mononucleosis, hemolysis tends to develop 1-2 weeks after the onset of illness, but it may occur simultaneously or up to 2 months after onset. [25] Furthermore, increased expression of I/i antigens have been described on hemoglobin SS (HbSS) erythrocytes, which suggests that such patients may have increased susceptibility to cold-mediated hemolysis. [26]

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