Symptoms of Cold Agglutinin Disease

Cold agglutinin disease (CAD) is a rare disorder in which the immune system mistakenly attacks red blood cells, resulting in anemia.

The cause of CAD is not known. Some patients may develop CAD as a symptom of other illnesses, such as an infection, autoimmune disease, or some types of cancer.

The symptoms of CAD can be made worse by cold exposure. Even eating or drinking cold substances can cause patients discomfort. Symptoms of CAD can include one or all of the following:


Because CAD causes anemia, there are not enough blood cells to carry oxygen to all the tissues in the body. This can result in muscle weakness and fatigue. Patients may not feel rested even after getting a full night’s sleep, and may require more energy to complete daily tasks.

Raynaud’s syndrome

CAD can cause a condition known as Raynaud’s syndrome (also called Raynaud’s phenomenon), in which the blood vessels “pinch off” or constrict when patients are exposed to cold. Individuals may see their hands or feet turn very pale or red, and feel numb and prickly.

Joint pain

More than 80% of people with CAD experience joint or chest pain during a hemolytic episode. A hemolytic episode is a flareup of the immune attack on the red blood cells. This pain can range from mild to extreme.

Jaundice or skin discoloration

The skin of people with CAD may have blotchy purple areas, almost like bruises beneath the skin. Some patients may develop jaundice, a yellow tint to the eyes and skin, which indicates that the liver is having trouble metabolizing wastes associated with blood cells breaking down.

Heart problems

Many individuals with CAD develop heart problems, which can include irregular heartbeat, called arrhythmia, heart murmur, an enlarged heart, or cardiomegaly, or even heart failure. This might be caused by the heart having to work harder to ensure that tissues receive enough oxygen with fewer red blood cells.


Last updated: July 29, 2019


Cold Agglutinin News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.