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Cold Agglutinin Disease - Causes, Symptoms, Diagnosis and Treatment

Published on Apr 05, 2022 and last reviewed on Apr 07, 2022   -  4 min read


Cold agglutinin disease is a condition that makes our body's immune system attack our own red blood cells. To know more, read the article below.


What Is Cold Agglutinin Disease?

Cold agglutinin disease (CAD) is a type of autoimmune hemolytic anemia that occurs in rare cases. This disease is also known as cold antibody hemolytic anemia. In this condition, the immune system present in the body mistakes the red blood cells that are present in the body as harmful pathogens and begins to destroy them by attacking the red blood cells.

Primarily, this condition is caused due to long-time exposure to cold temperatures. This happens when the person is living in a cold environment; their IgM (immunoglobulin M) antibodies which are present in the body, get attached to the red blood cells. These red blood cells become bound to one another, which causes clumps (agglutin) and leads to premature destruction of the red blood cells.

This condition is also known by the term cold antibody hemolytic anemia. The problems associated range from minor fatigue to major heart failure. Statistically, this condition affects only one person in 300,000 people; also, when compared to men, it is mostly women who are affected.

What Are the Causes of Cold Agglutinin Disease?

Cold agglutinin disease can be present as a primary disease or a secondary condition to any other underlying disease. As far as primary cold agglutinin disease is concerned, there are no proper cases. Doctors consider it to be idiopathic and do not know the exact reason behind it.

But in the case of secondary cold agglutinin disease, there are certain conditions that are associated with causing it; they are:

There has not been any evidence that cold agglutinin disease is inherited from an affected person. Hence cold agglutinin disease is not a hereditary disease. In certain cases, cold agglutinin disease can be multifactorial. Environmental conditions and genetic conditions combine and interact to develop the condition.

What Are the Symptoms of Cold Agglutinin Disease?

As mentioned earlier, cold agglutinin disease is triggered or worsened due to cold exposure. There are cases wherein the symptoms start due to viral infection. Hence this cold agglutinin disease generally prevails during the winter season. The symptoms might start gradually and become worse for some people, and for others, they might arise suddenly.

Cold agglutinin disease (CAD) has symptoms that are similar to that of hemolytic anemia, but the severity of the symptoms differs based on the severity of the anemia. Some of the common symptoms include:

There are certain specific symptoms in people with poor circulation, such as irregular periods in women and bluish discoloration of the feet and hands, also known as Raynaud’s disease. In addition, if CAD is secondary and is caused by any other underlying condition, then the symptoms differ, such as:

How Is Cold Agglutinin Disease Diagnosed?

Diagnosing cold agglutinin disease is quite simple. If the doctor suspects that the patient is suffering from cold agglutinin disease, then he or she will run a blood test to check the blood cell count. This is done to check if the patient is suffering from anemia or a low level of red blood cells. This test will also show evidence of any binding or clumping of the blood cells that causes agglutin.

When this test shows signs of cold agglutinin disease, then a test called a direct antiglobulin test, or Coomb’s test is performed to look for the antibodies that are responsible for killing the red blood cells. The doctor will also examine and feel the middle part of the abdomen to check for any enlargement of the spleen or liver.

How Is Cold Agglutinin Disease Treated?

This disease can happen alone (primary cold agglutinin disease) or can occur due to other underlying conditions known as secondary cold agglutinin disease. Hence the treatment differs based on whether the condition is primary or secondary and the severity of the symptoms.

If the symptoms are very mild, then no medical treatment is required. These symptoms can be self-managed by staying out of cold temperatures as well as keeping the body warm; however, if the doctor observes a low red blood cell count in the blood test, then the patient has to undergo a treatment called plasmapheresis.

This can also be achieved by performing a blood transfusion. Though these treatment options provide temporary relief and are considered to be short-term treatments, they do not help against the actual cause of the problem.

In the case of secondary cold agglutinin disease, the treatment methods will be focused on treating the underlying conditions while simultaneously managing the symptoms. For instance, if the condition is caused by a viral or bacterial infection, then the treatment will be focused on removing the infection. This makes the condition improve as the virus or the bacteria that caused the infection is out of the system.

If the condition is severe and the patient is highly anemic, the doctor might prescribe some medicines. The most commonly used medication for cold agglutinin disease is Rituximab, which attacks certain immune cells. Using Rituximab only is not sufficient; it can be combined with other medicines such as Bendamustine to stop the harmful cells from multiplying. If these combination medicines also do not work, the doctors might prescribe a drug called Bortezomib, which is used to treat multiple myeloma.


Cold agglutinin disease is a rare condition. In order to keep ourselves protected from cold agglutinin disease, it is important to stay out of cold temperatures and keep the body warm. The entire treatment will focus on the underlying cause and the severity of the symptoms. Book a consultation nearby or with us online at the earliest to keep your cold at bay.

Frequently Asked Questions


What Tests to Do to Confirm Cold Agglutinin Disease?

The following tests can help in the diagnosis of cold agglutinin disease:

- Peripheral blood smear.

- Complete blood count (CBC).

- Reticulocyte count.

- Serum protein electrophoresis and serum immunoelectrophoresis (immunofixation).

- Direct antiglobulin test (DAT) (direct Coombs test).


Is Cold Agglutinin a Common Disease?

Cold agglutinin affects about one in 3,00,000 people. This disease affects women more than men and affects people aged above 60.


How to Treat Cold Agglutinin Disease?

Mild cases of cold agglutinin disease (CAD) can be managed by avoiding extreme cold situations by taking proper precautions. If a person needs pharmacological treatments for management, proper trials must be taken.


Is Cold Agglutinin Disease Curable?

Cold agglutinin disease has an excellent prognosis. The symptoms completely resolve six months after the cure of the infection.


Is Cold Agglutinin Disease an Autoimmune Disease?

Yes, cold agglutinin disease (CAD) is a type of autoimmune hemolytic anemia (AIHA).


Is Cold Agglutinin Disease Serious?

Cold agglutinin disease is much more than avoiding colds. This disease is characterized by a malfunctioning immune system where the immune system attacks the body’s red blood cells and is triggered by cold situations. This can cause dizziness and can cause serious complications like heart failure.


What Triggers Cold Agglutinin Disease?

Your body has antibodies called cold agglutinin, and they can be triggered when the body’s temperature falls below the normal range.


What Happens When One Gets Cold Agglutinin Disease?

Cold agglutinin disease (CAD) is characterized by a malfunctioning immune system where your antibodies attack healthy red blood cells (RBC) and is triggered under cold conditions. And the person with CAD experiences the following symptoms:

- Cold feet or hands.

- Pale or yellow skin.

- Vomiting.

- Diarrhea.

- Dizziness.

- Painful legs, joints, or back.

- Ringing in your ears.

- Mood swings and irritability.

Article Resources

Last reviewed at:
07 Apr 2022  -  4 min read




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