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What is cold agglutinin disease?
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, such as:
- 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, but it has been seen in patients as young as 30.
Sometimes CAD might be referred to as primary CAD. That’s when CAD is not known to be caused by any other underlying condition. In some people, cold agglutinin antibodies are triggered by an underlying condition, like a viral infection. When this happens, it’s called Cold Agglutinin Syndrome (or CAS).
What is happening in my body?
If you’re living with cold agglutinin disease, certain abnormal bone marrow cells produce autoantibodies against red blood cells (called cold agglutinins) that 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 continuously 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.
Anemia
Anemia occurs when you do not have enough red blood cells or when your red blood cells do not function properly.
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, immune proteins called autoantibodies mistake healthy red blood cells for foreign threats, and then activate the complement pathway which destroys the healthy red blood cells.
What’s the connection between the complement pathway and hemolysis in CAD?
The complement pathway is a part of the immune system. Activation of the complement pathway may lead to hemolysis—the destruction of red blood cells. Here’s what can happen to a red blood cell as it moves through the complement pathway in someone with CAD.
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Red blood cell
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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.
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This leads to a complex chain of events that mark the red blood cell for destruction.
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At the end of the pathway, the marked cell is destroyed. This destruction is known as hemolysis, which can cause anemia and other complications.
What are the risks of cold agglutinin disease?
In CAD, hemolysis of red blood cells may cause fatigue, shortness of breath, and other symptoms. New findings show that CAD may be more serious than previously thought. A 10-year review of the medical histories of 425 people with cold agglutinin disease showed that they had a higher risk of stroke, heart attack, or blood clots (27% of patients with CAD vs 17% of patients without CAD experienced one of these events). More studies are needed to evaluate this risk.
What can your blood tell you about your health?
One way your doctor can keep an eye on your health is by looking at the different components of your blood. Below is some information on various blood tests your doctor may request. Your doctor may run all these tests or just a few—he or she will determine which tests are right for you based on your needs.
Hemoglobin:
usually found inside of red blood cells, this protein helps to transport oxygen and carbon dioxide throughout the body
Bilirubin:
a pigment that is released when hemoglobin is broken down
Lactate dehydrogenase (LDH or LD):
is an enzyme that is released when cells are destroyed
Haptoglobin:
a protein in the blood whose job it is to find hemoglobin that has been released from destroyed red blood cells and flag it for recycling
Reticulocytes:
these are the young (immature) red blood cells that are produced to replace red blood cells that have been destroyed
Antibody titer:
measures the concentration and strength of antibodies (such as cold agglutinins) in your blood
Mean corpuscular volume (or MCV):
is a measure of the average size and volume of red blood cells in your blood
Blood smear:
evaluates the shape, size, color, and arrangement of red blood cells as well as looks at your white blood cells and platelets
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
Be sure to talk to your doctor about potential treatment options that might be right for you.