/ Updated July 14th, 2022

Identifying & Diagnosing Cold Agglutinin Disease (CAD)

Creator: Laura Gesualdi-Gilmore
Published: 2022-06-05T16:20:38-04:00

: Dr. Rodrigo Edelmuth Written by: Laura Gesualdi-Gilmore
SurvivorNet

Details

Identifying Cold Agglutinin Disease (CAD) Can be Difficult

Because cold agglutinin disease (CAD) is so rare, getting the correct diagnosis can be difficult.
CAD can cause symptoms such as anemia, fatigue, and muscle weakness.
If a doctor suspects CAD, they may order a complete blood count (CBC) and/or a series of other tests to make the diagnosis.
Once a diagnosis is made, your doctor will look into whether an underlying condition caused CAD to help determine if treatment is needed.

Cold agglutinin disease (CAD) is a rare blood disorder that causes a person’s own immune system to destroy their red blood cells. The disease can be triggered by cold temperatures and can occur on its own or be caused by a handful of different ailments, including infections such as pneumonia, immune conditions like lupus, or blood cancers such as lymphoma or chronic lymphocytic leukemia (CLL).

The symptoms a person experiences with CAD will depend on what is causing the disease.

“The presentation of this disorder is with either destruction of red blood cells or changes in your hands and fingers when you go out in the cold,” Dr. Roy Smith, a hematologist/oncologist at the University of Pittsburgh, tells SurvivorNet. “It’s a cold-dependent disorder and it can be primary. That is, it’s idiopathic; we don’t know what causes it … It occurs in different settings that, for the patient, it tends to result in chronic anemia, fatigue. There is [also] a predisposition to having blood clots with it, and it tends to be a very chronic disorder.”

Common symptoms of CAD include:

Joint pain
Fatigue
Anemia
Muscle weakness
Abnormally pale skin

However, Dr. Smith stresses that because of the rarity of CAD, the disease may be difficult 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,” he explains.

Diagnosing CAD

Diagnosing CAD will likely require several tests, which will likely include 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. Dr. Smith explains that a doctor would need to look for any destruction of red blood cells, “then you’d look for the source of it.”

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 explains. To determine the source of red blood cell destruction after the CBC, a doctor may conduct another tests called a Coombs test, which is used to detect antibodies that act against the surface of your red blood cells. The presence of these antibodies would suggest hemolytic anemia (a type of anemia caused by the premature destruction of red blood cells).

Once a diagnosis is made, treatment will depend on whatif anythingis driving the CAD.

“You want to treat the underlying condition that's driving CAD,” Dr. Jun Choi, hematologist/oncologist at NYU Langone's Perlmutter Cancer Center, tells SurvivorNet. 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.”

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