What Is CAD?

Cold agglutinin disease, or CAD, is a rare autoimmune disorder in which self-targeting antibodies attack and destroy red blood cells at low temperatures.

Types of CAD

CAD can be divided into two types — primary and secondary CAD — depending on the underlying cause. In secondary CAD, the disease develops in association with another health condition, such as an infection or cancer. With primary CAD, the specific cause is unknown and other illnesses are not known to exist.

Causes of CAD

CAD is caused by a specific type of self-reactive antibodies called cold agglutinins. At cold temperatures — generally between 32 to 50 F (0 to 10 C) — cold agglutinins bind to red blood cells, causing them to clump together, or agglutinate, and ultimately die.

Symptoms of CAD

Red blood cells are responsible for carrying oxygen through the blood to all body tissues. In CAD and other types of anemia, tissues often do not receive enough oxygen, which can lead to fatigue and pain.

A common symptom of CAD is Raynaud’s syndrome, a condition in which blood vessels — usually in the fingers and toes — constrict when exposed to cold temperatures. Affected areas may turn pale, red, or blue, and patients may experience a numb or tingling sensation.

Red blood cell destruction can also cause the skin to become unusually pale or yellowish (jaundice). Some CAD patients may also develop acrocyanosis, or bluish skin discoloration.

Diagnosis of CAD

CAD usually is first suspected when a person notices certain symptoms when exposed to cold, or when a physical exam reveals potential signs of anemia. A variety of laboratory tests can be done on a patient’s blood to confirm the presence of anemia and detect cold agglutinins, confirming a diagnosis.

Treating CAD

In mild cases, CAD may not require medical treatment, with symptoms sufficiently controlled by avoiding exposure to cold temperatures and taking additional precautions under specific circumstances, including during hospitalization.

Taking supplements of folic acid, a man-made version of a vitamin the body uses to make red blood cells, may also help to alleviate symptoms of anemia. Treatment with a hormone called erythropoietin may help to spur the production of new red blood cells.

In more severe cases, medications like rituximab, which works by destroying antibody-producing immune B-cells, may be needed. Rituximab may be used on its own to treat CAD, or in combination with other therapies like fludarabine.

Blood transfusions or plasmapheresis (plasma exchange therapy) may also be used to help manage severe cases of CAD.


Last updated: Oct. 15, 2021


Cold Agglutinin Disease 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.