COLD AGGLUTININ DISEASE

What is cold agglutinin disease? What is CAD?

Cold agglutinin disease (CAD) is a form of autoimmune hemolytic anemia (AIHA), which means the immune system mistakenly attacks and destroys red blood cells.

People living with CAD may experience symptoms like:

  • Fatigue
  • Weakness
  • Shortness of breath
  • Light-headedness
  • Chest pain
  • Irregular heartbeat
  • A bluish color or discomfort of the hands and feet

These symptoms may get worse if you have a compromised immune system or an infection, or if you’re exposed to cold temperatures.

The average age of onset for CAD is 58 years old, but it has been seen in patients as young as 30.

To learn more about the science behind CAD, read this page and watch this video.

What’s happening in my body?

Anemia occurs when you do not have enough red blood cells or when your red blood cells do not function properly

If you’re living with cold agglutinin disease, certain abnormal bone marrow cells (called cold agglutinins) activate a part of your immune system known as the complement pathway. This activation results in ongoing, constant destruction of red blood cells (hemolysis). Even if you’re not exposed to the cold, the ongoing hemolysis could lead to complications like anemia, a lack of red blood cells or hemoglobin in the blood that can cause severe fatigue.

When you have CAD and red blood cells are destroyed prematurely, they are not able to do the vital job of carrying oxygen throughout your body. If your organs and tissues don’t get enough oxygen, they can’t function normally—making you feel tired.

Let’s take a closer look at the immune system and the complement pathway.

Your immune system normally helps the body by eliminating foreign threats such as bacteria.

In cold agglutinin disease, a part of the immune system called the complement pathway mistakes healthy red blood cells for foreign threats and destroys them.

What’s the connection between the complement pathway and hemolysis in CAD?

The complement pathway is the part of the immune system where the destruction of red blood cells, or hemolysis, is activated. Here’s what can happen to a red blood cell as it moves through the complement pathway in someone with CAD.

Red blood cell
In cold agglutinin disease, the cold agglutinin antibody mistakenly attaches to the red blood cell and activates the complement pathway. The pathway starts with complement protein 1 (C1 in the illustration) binding to the red blood cell.
This leads to a complex chain of events that mark the red blood cell for destruction.
At the end of the pathway, the marked cell is destroyed. This destruction is known as hemolysis, which can cause anemia and other complications.

Red blood cell

In cold agglutinin disease, the cold agglutinin antibody mistakenly attaches to the red blood cell and activates the complement pathway. The pathway starts with complement protein 1 (C1 in the illustration) binding to the red blood cell.

This leads to a complex chain of events that mark the red blood cell for destruction.

At the end of the pathway, the marked cell is destroyed. This destruction is known as hemolysis, which can cause anemia and other complications.

The complement pathway in action

Watch this video for an in-depth look at what’s happening in your body when you have CAD. See how the complement pathway activates hemolysis, find out why that's important, and learn about ongoing research efforts.

See transcript

Cold agglutinin disease (CAD) is a rare, severe blood disorder. It’s a form of autoimmune hemolytic anemia, which means the immune system mistakenly attacks and destroys red blood cells.

In cold agglutinin disease, certain abnormal bone marrow cells produce antibodies called cold agglutinins, which activate a part of the immune system known as the complement pathway. This activation results in the constant destruction of red blood cells, known as hemolysis.  

Here’s how it works:

  • The cold agglutinin antibody mistakenly attaches to a red blood cell and activates the complement pathway
  • The pathway starts with a protein called C1 binding to the red blood cell. This leads to a complex chain of events that marks the red blood cell for destruction
  • At the end of the pathway, the marked cell is destroyed. This destruction is known as hemolysis

In people with CAD, the destruction of red blood cells, or C1-activated hemolysis, is happening all the time. It can cause anemia, along with severe fatigue. That’s because red blood cells are destroyed prematurely and are not able to do the vital job of carrying oxygen throughout your body. If your organs and tissues don’t get enough oxygen, they can’t function normally—making you feel tired.

Recent studies have shown that CAD may be more serious than previously thought. A 10-year review of the medical histories of people with CAD showed that they had a higher risk of stroke, heart attack, or blood clots. Additionally, patients with CAD are also at risk of experiencing sudden drops in their hemoglobin that may require emergency treatment.

Though researchers are getting closer, there are currently no treatments approved specifically for cold agglutinin disease. Research is being done every day to find more answers for people living with this rare condition.

Sanofi Genzyme is committed to transforming the care of people living with rare blood disorders.

What are the risks of cold agglutinin disease?

New findings show that CAD may be more serious than previously thought. A 10-year review of the medical histories of people with cold agglutinin disease showed that they had a higher risk of stroke, heart attack, or blood clots.

Since hemolysis is constantly happening in people with CAD, it’s important to pay close attention to how you are feeling and be in regular contact with your doctor. It’s also a good idea to keep track of your blood test results so you and your doctor have a better understanding of how CAD is affecting you.

Treating cold agglutinin disease

Though researchers are getting closer, there are currently no treatments approved specifically for cold agglutinin disease. In the meantime, doctors may recommend avoiding the cold or prescribe medications to help manage CAD.

There is a real need for approved medicines to treat CAD. Research is being done every day to find more answers for people living with this rare condition.

Sanofi Genzyme is committed to helping transform the lives of people with cold agglutinin disease and other rare blood disorders. We’re currently in the process of investigating solutions for people just like you.

If you’re interested in learning about ongoing clinical studies for CAD, talk to your healthcare provider.