What are some common symptoms of cold agglutinin disease?

In CAD, the binding of cold agglutinin antibodies to healthy red blood cells can have a few consequences. The binding of these antibodies to the red blood cells triggers the classical complement pathway starting with a protein called C1, marking them for destruction in a process known as haemolysis. 

Also, cold agglutinin antibodies may bind to red blood cells in small blood vessels, where the temperature is lower than body temperature, and may cause them to clump together (this is called agglutination) and interfere with blood flow through these vessels.

Agglutinated blood cells

As a rare condition, there have been few studies looking at symptoms. While it’s recognised that people with CAD report a variety of symptoms, there are some common ones that can be caused by haemolysis or agglutination. The symptoms of CAD can vary from person to person and may include fatigue, weakness, shortness of breath, and circulatory symptoms.

Blocked blood vessel

Symptoms caused by haemolysis

Haemolysis is the destruction of red blood cells. Red blood cells deliver oxygen to cells throughout your body. Anaemia (low amount of red blood cells) can result when chronic haemolysis destroys more red blood cells than your body can replace. This can lead to some of the common symptoms associated with CAD, such as:

Fatigue icon


Shortness of breath icon

Shortness of Breath

Muscle weakness icon

Muscle Weakness

Another consequence of haemolysis is the contents of red blood cells spilling into the blood stream. The haemoglobin from the red blood cells breaks down into a pigment called bilirubin that builds up. High levels of bilirubin may be noticeable as dark urine or jaundice (yellowing of the skin and whites of the eyes).


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Symptoms caused by agglutination

When cold agglutinins bind red blood cells, the clump of cells and antibodies can slow down or potentially block the flow of blood in small blood vessels. This can be a cause of the circulatory symptoms associated with CAD and for fingers and toes turning a bluish or reddish color.

Agglutination icon

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