Saturday, March 8, 2014


Cold-Agglutination Disease

Background Information of Cold Agglutinin disease

All individuals have circulating antibodies directed against their own RBCs, but fortunately their concentrations are often too low to trigger disease (titers under 64 at 4°C). Cold agglutinin disease is an autoimmune disease used to describe patients that have excessive concentrations (titers over 1000 at 4°C) of circulating antibodies directed against RBCs. These antibodies usually come in the form of IgM. It is a form of autoimmune hemolytic anemia, specifically one in which antibodies only bind red blood cells at low body temperatures, typically 28-31°C.

Once blood samples are taken from a patient with cold agglutinin disease, the temperature of the blood sample will naturally fall below 37°C. As a result, antibodies (IgM) will begin to bind to the polysaccharide region of glycoproteins on the surface of RBCs (typically the I antigen, i antigen, and Pr antigens). Hence, there will be numerous "clumping" of RBCs seen.

Cellular Description

The hall mark of cold agglutinin disease is the presence of numerous "clumps" of RBC. This phenomenon is usually accompanied by a spurious elevation in MCV, a discrepancy between the hemoglobin and the hematocrit, the latter falsely reduced and consequently a MCHC value greater than 36%. Since MCHC rarely exceeds 36% in health or disease, it is an important clue to the spurious nature of the macrocytosis caused by cold agglutinins.  

How to resolve this problem to assess the PBFs
  1. warm a slide up at 37°C and incubate the EDTA sample at 37°C for 15 minutes
  2. make a thin smear and dry (fix) the sample at 37°C for 5 minutes
  3. Stain as usual with wright smear and read under the microscope 

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