Cold agglutinin disease (CAD)

Cold agglutinin disease is a form of autoimmune hemolytic anemia in which the immune system produces antibodies, usually of the IgM type, that become active at cooler temperatures and attach to red blood cells in the smaller blood vessels near the body's surface. This binding activates part of the immune system called the complement pathway, and the affected red blood cells are broken down faster than the body can replace them.

CAD is rare and research describes a prevalence estimated around 1 to 3 cases per 100,000 people in the United States, with cold climates associated with higher rates than warmer ones. It tends to appear later in life, around the mid-sixties on average, and is more common in women, and exposure to cold typically brings on or worsens symptoms.

Common signs

Fatigue and shortness of breath from anemia, a fast heartbeat, pale or yellowish skin, dark urine, and bluish or painful fingers, toes, ears, or nose on exposure to cold, which often eases with warming.

This is a plain-language summary for orientation, not a diagnosis. Mechanisms are described as current understanding, not settled fact. Work with your own clinician for your care.