Symptoms of CAD

Cold agglutinin disease (CAD) is a rare disorder in which the immune system mistakenly attacks red blood cells at low temperatures, resulting in anemia, or a lack of red blood cells to transport oxygen to all tissues and organs in the body.

CAD symptoms, which can appear suddenly or gradually, typically worsen when patients are exposed to cold temperatures. Most CAD symptoms are a direct consequence of red blood cell destruction or circulatory problems.

Fatigue and pain

In CAD and other forms of anemia, there are not enough red blood cells to carry oxygen to all tissues in the body. This can result in weakness and fatigue, as the body is unable to keep up with energy demand. People with CAD symptoms may include feeling tired even after a full night sleep, and taking more effort to complete day-to-day tasks.

In CAD, red blood cells tend to clump together before being destroyed. These clumps can interfere with blood flow and block small blood vessels. When blood flow is obstructed and tissues are not receiving enough oxygen, patients also may experience pain. It is common for people with CAD to experience pain in joints, such as the shoulders, hips, knees, ankles, and wrists. CAD may cause pain in the chest, back, or legs. Symptoms also may include headaches and sensations of dizziness.

Raynaud’s syndrome

CAD can cause a condition known as Raynaud’s syndrome, or Raynaud’s phenomenon, in which blood vessels narrow, or constrict, when patients are exposed to cold temperatures. This most commonly affects the fingertips and toes, but also may happen in the nipples, ears, nose, and lips.

Affected areas may become very pale or blue, and feel numb and prickly due to the lack of blood flow. Once warmth is restored and blood circulation improves, sensation returns and the affected areas may turn red and swell. At this point, patients may experience a throbbing and tingling sensation.

Raynaud’s syndrome is not unique to CAD. It also may develop in people with other autoimmune diseases, such as scleroderma, lupus, rheumatoid arthritis, and Sjögren’s syndrome. Raynaud’s syndrome sometimes occurs in the absence of any other disease, in which case it is classified as primary Raynaud’s syndrome.

Skin discoloration

People with CAD may have unusually pale skin due to anemia. They also may have acrocyanosis, a bluish discoloration of the skin that occurs due to poor blood circulation in certain areas. Acrocyanosis most commonly affects the hands and feet, although it can also affect the ears, nose, and nipples.

Some patients may experience livedo reticularis, a striking reddish-brown to a bluish blotched and reticular (net-like) pattern of blood vessels surrounding a pale central area of skin. Livedo reticularis occurs most often on the legs. It happens because of disturbances in blood flow and reduced oxygen supply to the skin.

Some patients may develop jaundice, a condition in which the skin and eyes acquire a yellowish tint. This occurs because of a buildup of a yellow-brownish protein, called bilirubin, which is produced when red blood cells are broken down. High bilirubin levels also can cause urine to become unusually dark in color.

Heart problems

When blood flow is obstructed in CAD, it can force the heart to work harder to pump blood. Disintegrated red blood cells can make the blood thicker, making it harder for the heart to pump blood through the body.

The added strain on the heart can lead to several problems, such as high blood pressure, an irregular heartbeat (arrhythmia), heart murmur, an enlarged heart, or even heart failure — a condition in which the heart is no longer able to adequately pump blood to the body’s tissues.

CAD patients also may be at increased risk of clotting-related diseases, which can obstruct blood flow and cause damage to organs, or lead to a heart attack.


Last updated: Sept. 30, 2021


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.