The Five Key Questions To Ask Your Doctor About Cold Agglutinin Disease

Cold agglutinin disease is a rare type of blood disorder characterized by the destruction of red blood cells and a reaction to cold temperatures which is where the “cold” in the name comes from.

The reaction to the cold happens when certain proteins that normally attack bacteria (known as IgM antibodies) alternatively decide to attach to red blood cells and form clumps (known as agglutination) which leads to their premature destruction.

Symptoms of CAD

As a result, anemia (low red blood cells) and other issues can occur with symptoms potentially getting worse due to lower temperatures.

"Symptoms of CAD are more apparent and severe when you're exposed to cold temperature," Dr. Jun Choi, hematologist-oncologist at NYU Langone's Perlmutter Cancer Center, told SurvivorNet. "For example, during winter time, or when you are touching something cold, it can trigger the disease to act up. So, when your anemia becomes severe, your hemoglobin goes down. Then you can have symptoms of anemia."

These symptoms may include:

• Fatigue
• Shortness of breath
• Dizziness

In addition, people with CAD may also experience symptoms associated with autoimmune disease, such as:

• Finger tips turning blue due to lack of oxygen
• Malaise (feeling unwell in general)

Diagnosing CAD

There are signs of CAD to look out for, but, because the disorder is so rare, it’s tricky to diagnose.

"It's really very, very rare, and it's a disease that is very, very commonly misdiagnosed because the guys out the real world just don't see very much of it, and you have to think about it in order to make the diagnosis," Dr. Roy Smith, a hematologist-oncologist at University of Pittsburgh Hillman Cancer Center, told SurvivorNet.

To properly diagnose the disorder, a doctor will likely perform several tests including a complete blood count (CBC) to measure hemoglobin (the oxygen carrying protein in red blood cells), as well as red blood cells, white blood cells, hematocrit, and platelets.

When a person has CAD, their CBC report may include things like:

• Low hemoglobin
• Larger than normal red blood cells
• Red blood cells that look bluer than average (polychromasia)

"If you looked at the peripheral blood smear under a microscope… then what you typically see is that red cells are clumped around each other," Dr. Smith said.

Next, a Coombs test may be conducted by your doctor to help determine why your red blood cells are being destroyed This test detects antibodies that act against the surface of your red blood cells, and their presence would suggest hemolytic anemia (a type of anemia caused by the premature destruction of red blood cells).

What Causes CAD?

CAD can occur on its own, but it can also be caused be several different illnesses including infection, autoimmune disease or blood cancer.

"It's idiopathic, we don't know what causes it," Dr. Smith said. "And it can be secondary to infections, like infectious mononucleosis or maybe an underlying lymphoma, even. So, it occurs in different settings that, for the patient, it tends to result in chronic anemia, fatigue. There is a predisposition to having blood clots with it, and it tends to be a very chronic disorder."

It’s important for your doctor to figure out if there is an underlying cause because that can impact your course of treatment. But having CAD does not always mean you need treatment.

"When the disease is diagnosed, you want to push forward the standard therapy, and you want to make sure the treatment is necessary because some people do not need treatment," Dr. Choi said. "Some people just have to avoid cold temperature, and that should be adequate to maintain adequate level of blood cells."

Questions To Ask Your Doctor about Cold Agglutinin Disease

Once you’ve received a cold agglutinin disease diagnosis or even if you or a doctor thinks you have it, it’s important to make sure any questions you have about the disorder are addressed. Below are some suggestions to get you going, but as always you should try to remember that you deserve to have all your questions answered. Don’t limit yourself to these five questions if there’s more you’re needing or wanting to know about this rare disorder.

1.  Since CAD is easily misdiagnosed, is there a possibility that my symptoms are being caused by something else?

• As we’ve said before, CAD is very rare disorder, and that means it can be hard to diagnose. If you or any medical professional thinks you might have it, it might be a good idea to see a hematologist that is familiar with CAD to make sure you’re being diagnosed correctly.

2.  Do I have an underlying condition causing my CAD?

• Not all people with CAD have an underlying cause to point to. But it’s important that doctors properly investigate whether there is a root cause because that can affect your treatment going forward.
• "You want to treat the underlying condition that's driving CAD," Dr.  Choi said. In cases where the disease is caused by a blood cancer, "the standard-of-care for that condition is a chemotherapy or therapy to target those lymphoma cells. When CAD is acting up significantly, then you want to treat the [disease] itself."

3.  Do I need treatment? And, if so, what will that treatment process look like for my specific case of CAD?

• Some people with CAD do not need 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," Dr. Smith said. "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 treatment is necessary, options can differ from person to person. Below are some examples of treatment options, but they vary greatly depending on the root cause if there is one:
  • Rituxan a monocolonal antibody that is considered a "first-line" therapy for CAD, meaning it can be given as a first attempt at treatment. "A fair number of people respond [to rituximab]," Dr. Smith said. "It's a pretty simply therapy to give, although you have to give it multiple times."
  • Rituxan plus chemotherapy
  • Sutimlimab (Enjaymo) this drug was recently approved in February 2022.
  • Antibiotics
  • Antivirus medication
  • Plasmapheresis (filtering your blood to get rid of antibodies that are causing the CAD)
  • Blood transfusion

4.  Should I make any lifestyle changes while I’m being treated for or living with CAD?

• People with CAD should try 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."
• People with CAD should stay bundled up and warm in the winter as well as in summer months when rooms may be cold from air conditioning.
• Avoiding cold food and drinks might also be a requirement.
• Talk with our doctor about ways to keep your CAD from progressing

5.  Are there any other precautions I should take as someone with CAD?

• You should always ask your doctor about ways to stay safe with CAD.
• Dr. Smith recommends particular 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 said. "Some of this stuff is just basic care, but it does make a difference for this particular group of people."
• In addition, if people with CAD undergo surgery where the operating room is cold or they receive 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."

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