Warm autoimmune hemolytic anemia and cold agglutinin (NORD)

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Warm autoimmune hemolytic anemia and cold agglutinin (NORD)

Information for patients and families

The National Organization for Rare Disorders (NORD)

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Thyroid eye disease (NORD)

Bile synthesis disorders (NORD)

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Short bowel syndrome (NORD)

Essential thrombocythemia (NORD)

Myelofibrosis (NORD)

Polycythemia vera (NORD)

Sickle cell disease (NORD)

Waldenstrom macroglobulinemia (NORD)

Warm autoimmune hemolytic anemia and cold agglutinin (NORD)

Congenital athymia (NORD)

Cytomegalovirus infection after transplant (NORD)

Post-transplant lymphoproliferative disorders (NORD)

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Alagille syndrome (NORD)

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Congenital cytomegalovirus (NORD)

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Fabry disease (NORD)

Gaucher disease (NORD)

Glycogen storage disease type II (NORD)

Metachromatic leukodystrophy (NORD)

Mucopolysaccharide storage disease type 1 (Hurler syndrome) (NORD)

Mucopolysaccharide storage disease type 2 (Hunter syndrome) (NORD)

Mycobacterium avium complex (NORD)

NGLY1 deficiency (NORD)

Niemann-Pick disease types A and B (NORD)

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PIK3CA-related overgrowth spectrum (NORD)

Tay-Sachs disease (NORD)

Zellweger spectrum disorders (NORD)

Early infantile epileptic encephalopathy (NORD)

Opsoclonus myoclonus syndrome (NORD)

Spinocerebellar ataxia (NORD)

Narcolepsy (NORD)

Focal segmental glomerulosclerosis (NORD)

IgA nephropathy (NORD)

Pulmonary arterial hypertension (NORD)


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.


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.


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