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When the number of red blood cells in your body is too low, this can result in anemia. It’s estimated that more than 1.6 billion people in the world have anemia.

One kind of anemia is called hemolytic anemia, or anemia caused by the destruction of red blood cells. There are various kinds of hemolytic anemias, including cold agglutinin disease (CAD).

Read on to learn more about this condition.

CAD is a disease in which a B-cell bone marrow disorder causes autoimmune hemolytic anemia. It makes up about 15 percent of autoimmune hemolytic anemias.

It usually occurs in people between the ages of 40 and 80 and is more common in older adults. The median age at which people receive a diagnosis is 65 years old.

The prevalence of this condition is estimated to be about 16 people per million. It develops in one person per million each year.

There are two types of CAD: primary and secondary. Primary CAD is when the triggering factor is unknown and there’s no other condition causing it. Secondary CAD is when it’s associated with an underlying disorder. This occurs in up to 70 percent of people living with CAD.

Underlying disorders associated with CAD include:

Many people living with CAD have symptoms of hemolytic anemia. Symptoms and their severity can vary depending on how serious your anemia is. These symptoms can include:

Some of these symptoms are caused by hemolysis, which is the destruction of red blood cells.

If you’re living with CAD, you may also have:

Your immune system typically produces antibodies that attach to invading cells and destroy them. When antibodies bind to red blood cells instead and think they’re targets, CAD can occur. One of these antibodies is IgM, which causes many CAD cases in people.

When antibodies attack healthy tissues, they’re called autoantibodies. When these autoantibodies are active in CAD, they can cause hemolysis if they’re exposed to cold temperatures.

Once your red blood cells are tagged by a cold-induced antibody, they clump together and attach to proteins called complements. These are also part of your immune system. When this happens, the red blood cells are then destroyed.

If the underlying cause of all this is not known, it’s considered primary CAD.

When CAD is a secondary disorder, it’s associated with or caused by different disorders like an infectious disease or connective tissue disorder.

Medical professionals can use several factors to help diagnose CAD. These can include:

  • your detailed medical history
  • a clinical evaluation
  • finding characteristic symptoms
  • blood tests, particularly those measuring your hemoglobin and hematocrit (the percentage of red blood cells present)

If a medical professional suspects that your hemolytic anemia is autoimmune, they’ll do a Coombs test. This test detects antibodies attached to your red blood cells or other biological components.

Once this is done, the medical expert will do a thermal amplitude test, which looks at blood samples at different temperatures. They will be able to see how your antibodies react at different temperatures. This determines how much cold agglutinin is present.

Treatment for CAD depends on the severity of the disease, the symptoms you’re having, and any underlying causes. If your symptoms are mild or hemolysis seems to be slowing down, you may not need any treatment.

If hemolysis is increasing, medication might be necessary. Rituximab is the standard treatment for CAD. It may be combined with certain chemotherapy drugs or with prednisone.

Rituximab targets the white blood cells that make the antibodies that destroy your red blood cells. Rituximab is also used to treat any relapses.

If there’s another condition causing CAD, that condition is treated.

If you have rapid hemolysis or severe anemia, you might need blood transfusions or a plasma exchange. But these do not actually treat your anemia. They only relieve symptoms temporarily.

Other treatments include avoiding cold temperatures when possible, especially to your head, face, and extremities. Prewarming intravenous (IV) fluids are also recommended.

Risk factors can increase your chance of developing a disease. Having one or more risk factors does not mean you’ll definitely develop the disease. It means that you’re at a higher risk.

Risk factors for CAD can include:

  • being female
  • having an associated condition previously listed
  • living in a colder climate

According to a 2020 report that categorized people as men and women, CAD is almost twice as common in women than men.

The outlook for people with CAD can vary widely. It may depend on things like the severity of the disease and your symptoms, and whether you have an underlying condition.

If an infection or unknown condition causes CAD, your outlook is typically good to excellent. This is especially true if you avoid unnecessary exposure to cold temperatures.

But if HIV or certain types of cancers cause CAD, the outlook is typically less favorable. This is because of the characteristics of the underlying illnesses.

CAD is a rare type of anemia that can cause significant symptoms, leading to illness and impaired quality of life. While it is not cancer, it may be caused by certain kinds of cancer, as well as various other conditions.

Your treatment and outlook can vary, depending on a variety of factors. If you have CAD, talk with your doctor about your treatment options and the steps you can take to minimize symptoms.