The Science Behind Cold Agglutinin Disease Symptoms

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 hemolysis.

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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 hemolysis.

Hemolysis Process

Red blood cell

The binding of cold agglutinin antibodies triggers the C1 protein to also bind to the red blood cell

This marks the cell for destruction

The red blood cell is destroyed in a process known as hemolysis

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 can interfere with blood flow through these vessels.

Agglutinated Blood Cells, Blocked Blood Vessel

As a rare condition, there have been few studies looking at symptoms. While it’s recognized that people with CAD report a variety of symptoms, there are some common ones that can be caused by hemolysis or agglutination.

Symptoms caused by hemolysis

Hemolysis is the destruction of red blood cells. Red blood cells deliver oxygen to cells throughout your body. Anemia (low amount of red blood cells) can result when chronic hemolysis destroys more red blood cells than your body can replace. This can lead to some of the common symptoms associated with CAD like:

Symptoms Caused by Hemolysis
Fatigue icon

Fatigue

Shortness of Breath icon

Shortness of Breath

Weakness Icon

Weakness

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Another consequence of hemolysis is the contents of red blood cells spilling into the blood stream. The hemoglobin from the red blood cells break 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).

Bilirubin and Jaundice process

Hemolysis causes hemoglobin to be released from red blood cells

Hemoglobin broken down

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 bluish/reddish in color.

Agglutination Icon

"If I put my hands in water that was too cold, then they would start to turn colors. Or if I went outside when it was the cool time of the day and tried to do something, as I was out there longer, it got to the point when then I could start to feel my skin tightening up. And then I could notice my fingers maybe starting to turn colors."

-FRED Person living with CAD