Cold agglutinins are autoantibodies produced by a person’s immune system that mistakenly target red blood cells (RBCs). They cause RBCs to clump together when a person is exposed to cold temperatures and increase the likelihood that the affected RBCs will be destroyed by the body. This test detects and measures the amount of cold agglutinins in the blood.

When the presence of cold agglutinins in a person’s blood leads to significant RBC destruction, it can cause hemolytic anemia and lead to a low RBC count and hemoglobin. This rare form of autoimmune hemolytic anemia is known as cold agglutinin disease. Cold agglutinin disease may be primary or secondary, induced by some other disease or condition.

Primary cold agglutinin disease typically affects those who are middle age to elderly, and it tends to continue over time (chronic). Secondary cold agglutinin disease may affect anyone and may be acute or chronic, temporary or persistent. It may cause hemolytic anemia to a greater or lesser degree and is associated with a variety of conditions.

The cold agglutinin test is not routinely ordered. It is a test that has been available for a long time, but it has become less commonly used as more specific tests for secondary causes, such as Mycoplasma pneumoniae infection, have become available.