Cold agglitinin disease (CAD) is a rare type of autoimmune hemolytic anemia. With CAD, cold temperatures activate your immune system to destroy red blood cells. As a result, you may experience anemia symptoms that range from mild to severe. Your healthcare provider may recommend lifestyle changes or prescribe medicines to treat cold agglutinin disease.
Cold agglutinin disease (CAD) is a rare blood condition that occurs when your immune system attacks your red blood cells. Your immune system makes proteins called antibodies that destroy harmful germs that enter your body. With CAD, your immune system releases an autoantibody, or “cold agglutinin,” that attacks healthy red blood cells.
CAD causes you to have too few red blood cells. Having enough red blood cells is essential because these cells carry oxygen throughout your body. The oxygen powers your cells to make the energy your body needs to function.
Cold agglutinin disease is a type of hemolytic anemia. Hemolytic anemia involves not having enough red blood cells because they break down or die faster than your body can replace them.
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Cold agglutinin disease is most common in people assigned female at birth (AFAB) between the ages of 40 and 80. Most diagnoses occur in people in their mid to late 60s.
Cold agglutinin disease is rare. Approximately one in a million people get diagnosed each year. In the United States, people living with CAD range from 300 to 3,000.
Cold agglutinin disease can cause you to experience the symptoms of anemia. Anemia is a condition that involves not having enough red blood cells. Depending on what’s causing your anemia, it may be a life-long condition (chronic) or short-lived. Its impacts on your body can range from mild to severe.
For instance, with mild cases of CAD, symptoms may set in so slowly that you may have the condition for several years before receiving a diagnosis. CAD can lead to severe and even life-threatening heart conditions in emergency scenarios.
Related to its name — “cold” agglutinin disease — CAD causes most intense symptoms in cold climates or chilly weather.
The symptoms of CAD are often related to anemia and problems with blood circulation throughout your body. Symptoms of CAD that are related to anemia and poor circulation include:
You may also experience the symptoms of jaundice. As your red blood cells get destroyed, they release a yellowish substance called bilirubin. Bilirubin build-up leads to jaundice. Symptoms of jaundice include:
Cold agglutinin disease is a type of autoimmune hemolytic anemia. With CAD, cold conditions activate your immune system to make an autoantibody that flags your red blood cells for destruction. Your red blood cells clump together (agglutinate) in response. The clumped cells make an easy target for another part of your immune system, called macrophages, to destroy.
The process begins when temperatures are approximately less than 37 degrees Fahrenheit to 39 degrees Fahrenheit (3 degrees Celsius to 4 degrees Celsius).
CAD disrupts the regular timeline that your body needs to make healthy red blood cells. Red blood cells typically live for about 120 days. This period allows your bone marrow enough time to make new red blood cells to replace the dying ones.
Researchers aren’t sure what causes your immune system to attack healthy cells. It’s possible that CAD results from an underlying condition. This is called secondary CAD. When there doesn’t seem to be a relationship between CAD and another disease, CAD is called primary, or idiopathic.
Secondary CAD is associated with infections, autoimmune disorders and lymphoproliferative disorders, including:
Your healthcare provider will review your medical history and symptoms. They’ll run blood tests to determine whether you have hemolytic anemia and the autoantibodies associated with CAD.
Blood tests for diagnosing hemolytic anemia include:
Your healthcare provider will check for the autoantibody that attacks your red blood cells to determine if your hemolytic anemia is CAD. Tests include:
Once your healthcare provider confirms your diagnosis, they’ll explore whether your CAD is related to an underlying condition (secondary cold agglutinin disease).
Treatment may involve managing CAD with lifestyle changes and medications, depending on how severe your symptoms are. Emergencies may require blood transfusions.
Your healthcare provider will treat your underlying condition if you have secondary CAD.
CAD isn’t a preventable condition.
People diagnosed with CAD, on average, live as long as people their same age without CAD. According to a recent study, on average, people diagnosed at 68 are alive in their 80s.
A note from Cleveland Clinic
Your experience of cold agglutinin disease (CAD) depends on whether it occurs independently or is related to an underlying condition. The severity of your symptoms will also play an important role in how aggressive your treatments may be. Your healthcare provider may be able to cure your CAD by treating any related underlying conditions. Even if you have long-term CAD, avoiding cold temperatures and taking medicines as prescribed can help you manage anemia symptoms.
Last reviewed by a Cleveland Clinic medical professional on 06/03/2022.
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