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Warm autoimmune hemolytic anemia and cold agglutinin (NORD)



Patient care

Information for patients and families

The Primary School
Glut1 Deficiency Foundation
The National Organization for Rare Disorders (NORD)

Content Reviewers:

Kelly Johnson, MS

Warm autoimmune hemolytic anemia, also called WAHA, and cold agglutinin disease, also called CAD, are autoimmune hemolytic anemias.

Autoimmune refers to when the body’s immune system mistakenly attacks and destroys healthy cells; hemolytic refers to the destruction of red blood cells; and anemia refers to when the blood does not contain enough healthy red blood cells.

In WAHA, hemolysis occurs more frequently at body temperature, hence the name “warm.”

It is the most common autoimmune hemolytic anemia and can occur at any age.

In CAD, hemolysis occurs more frequently at cold temperatures, hence the name “cold,” usually between 37 to 39oF, or 3 to 4oC.

Conversely, CAD is less common and generally occurs between 40 to 80 years of age.

The symptoms of both WAHA and CAD vary depending on severity.

Symptoms often include dizziness, palpitations, shortness of breath, dark urine, pale skin, jaundice, and fatigue.

In severe cases, individuals may experience chest pain, confusion, fainting, and lethargy, as well as abnormalities in heart rate and blood pressure.

Individuals with WAHA may also develop an enlarged spleen, causing a full feeling in the abdomen.

Individuals may also develop blood clots that can form in the legs, called deep vein thrombosis, and cause symptoms such as pain, swelling, redness, and warmth in one leg.

Clots can detach and travel to the lungs, called pulmonary embolism, causing symptoms such as shortness of breath, chest pain, and coughing up blood.

Individuals with CAD may also experience circulatory symptoms such as cold fingers and toes, and painful bluish or reddish discoloration of the fingers, toes, ankles, and wrists, also called Raynaud phenomenon.

In WAHA and CAD the immune system produces autoantibodies, which in this case are antibodies that target the body’s own healthy immune cells.

In WAHA, usually IgG antibodies tag the red blood cells which are then transported to the spleen to be destroyed.

In CAD, usually IgM antibodies tag red blood cells causing them to clump together or agglutinate.

Tagged red cells bind complement, one of the defense mechanisms present in the blood and they become targets for destruction by immune cells.

Primary or idiopathic WAHA or CAD occurs when the cause of autoantibody production is unknown.

Secondary WAHA or CAD occurs as a result of another condition, such as certain infections, autoimmune diseases, or cancers.

Diagnosis of WAHA or CAD begins with blood tests to confirm anemia through low hemoglobin, low hematocrit, and elevated reticulocytes.

Hemolysis is confirmed through low levels of haptoglobins, and elevated levels of bilirubin and lactate dehydrogenase.

Specialized testing, such as a Coombs test, detects the presence of WAHA or CAD-specific autoantibodies.


Warm autoimmune hemolytic anemia, or WAHA, and cold agglutinin disease, or CAD, are autoimmune hemolytic anemias characterized by the production of autoantibodies that cause early destruction of healthy red blood cells.

In WAHA, hemolysis occurs at the body temperature, whereas CAD is triggered by cold temperatures. Symptoms vary based on severity and include dizziness, palpitations, dark urine, pale skin, jaundice, and fatigue. Individuals with WAHA may also develop an enlarged spleen or deep vein thrombosis whereas individuals with CAD may experience the Raynaud phenomenon (a condition in which small blood vessels in the fingers and toes constrict).

Diagnosis involves a thorough clinical examination, including blood and specialized testing to identify the presence of anemia resulting from hemolysis. The Coombs test confirms the presence of autoantibodies associated with WAHA or CAD. Treatment is supportive and varies based on symptoms, and may include prednisone and other immunosuppressive or chemotherapy agents, and blood transfusions in severe cases.