Treating Cold Agglutinin Disease (CAD)

When someone has CAD, their immune system mistakenly attacks and destroys their own red blood cells. It's called "cold" agglutinin disease because when an affected person is exposed to cold temperatures, certain proteins that normally attack bacteria (known as IgM antibodies) instead attach themselves to red blood cells and bind them together into clumps (known as agglutination), and these cells are eventually prematurely destroyed. Symptoms, such as anemia (low red blood cells), fatigue, and shortness of breath, can get worse when temperatures are low.

Treatment Options For Cold Agglutinin Disease

Dr. Roy Smith, a hematologist-oncologist at University of Pittsburgh Hillman Cancer Center, says the first important decision is weighing the need for treatment.

“The first step is to determine whether (the patient) actually needs to be treated or not, because often it’s a matter of just telling a person to wear gloves or wear a coat or keep their house at a higher temperature or move to another place,” explains Dr. Smith. “That sounds funny, but the reality of the matter is, it’s not unreasonable to take a person who lives in Pennsylvania and say, ‘Look,  go to Florida or Arizona or someplace’.”

If a patient requires additional treatment, there are several options, notes Dr. Smith.

Rituxan, a monocolonal antibody

This drug destroys the cells that make antibodies. “If you give a person Rituxan, then all antibodies are reduced, including the cold pollutants and a fair number of people respond to it,” Dr. Smith says. The drug is given via multiple intravenous infusions. “When CAD is acting up significantly, then you want to treat the disease itself, and the first line treatment is rituximab,”  Dr. Jun Choi, hematologist-oncologist at NYU Langone's Perlmutter Cancer Center, tells SurvivorNet.

Rituxan plus chemotherapy

“There’s evidence that the combination of the monoclonal antibody Rituxan plus a chemotherapeutic agent, such as bortezomib (Velcade), or bendamustine are superior to either one alone,” Dr. Smith says.

Sutimlimab (Enjaymo)

Approved in February 2022, this drug inhibits the destruction of red blood cells and decreases the need for red blood cell transfusion in people with CAD.  Dr. Smith says that patients can generally see a “dramatic response” over four to six months. However, this medication does not address the issues with cold intolerance.

When CAD Is Caused by Cancer

"The treatment depends on what's causing the disease," Dr. Choi says.

If CAD is caused by a cancer like lymphoma, your doctor will need to treat that.

“The standard of care for that condition is chemotherapy,” Dr. Choi explained, adding that in some situations, a targeted therapy may be used as well.

“If a person had cold agglutinin disease associated with lymphoma, you would treat the lymphoma and the cold agglutinin disease generally goes away,” Dr. Smith explains.

When Cold Agglutinin Disease Has a Different Cause

When CAD is diagnosed in younger patients, it is typically caused by an infection, according to Dr. Choi, and treatment will again revolve around treating that root condition.

"CAD can also be caused by particular types of infections, such as mycoplasma, pneumonia, or other types of viruses … and this is more common in young patients," Dr. Choi explained. "When it is caused by those infections, you want to really treat those infections with antibiotics and antivirus medication. Usually the CAD goes away when the infections are treated."

When the disease is caused by some type of autoimmune disorder, like rheumatoid arthritis or lupus, treating the root cause also tends to be effective, resulting in the CAD going away, Dr. Choi said.

Living With Cold Agglutinin Disease

No matter what the root cause of the disease is, though, it’s important for patients to avoid extreme cold, which can make the condition worse.

"You want to avoid cold temperature, and when you need blood transfusions for low blood cells, we ask the blood bank to warm up the blood," Dr. Choi said. "So that cold temperature is avoided in every circumstances and that really helps to reduce the antibody from destroying your red blood cells and making your CAD progress."

Sometimes, when symptoms are mild, a patient will not need treatment, but staying warm should still be a priority to avoid causing the CAD to progress. This involves staying away from cold weather as well.

You may be able to avoid problems with CAD by staying bundled up and warm in the winter as well as in summer months when spending time in air conditioned rooms. For some patients, staying away from cold food and drinks may also be required. It’s important to talk to your doctor about what you can do to keep the disease from progressing.

It red blood cell counts are low, your doctor may also suggest filtering your blood to get rid of antibodies that are causing the CAD (which is called plasmapheresis) or a blood transfusion. However, if an underlying condition caused your CAD, these types of treatments will only provide temporary relief. The underlying condition will still need to be treated.

Dr. Smith also recommends caution when someone with CAD is hospitalized.

“When people are in the hospital, if I think someone has CAD, I will refuse to have them take any kind of IV fluid unless it’s warm. And these people have to have blankets and things,” Dr. Smith says. “Some of this stuff as just basic care, but it does make a difference for this particular group of people.”

Also, if someone with CAD is having a surgery where the operating room is kept cold, or they are given a blood transfusion with blood that’s not warmed, you can “exacerbate the destruction of the red blood cells…and you can have a catastrophe.”

Questions to Ask Your Doctor

• Was my CAD caused by an underlying condition?
• What are my treatment options?
• What activities and foods and/or beverages will I need to avoid?
• How will my CAD be monitored?

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