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Warm autoimmune haemolytic anaemia (wAIHA): symptoms, diagnosis and similarities with other conditions

Published 10 Apr 2022 • By Alizé Vives

The diagnosis of a disease is generally based on a clinical examination during which the doctor examines the patient. In addition, other examinations may be carried out: biological and immunological tests, medical imaging, biopsy, etc. 

The diagnosis of warm autoimmune haemolytic anaemia (wAIHA) can take some time because it can be mistaken for other diseases. It is therefore necessary to make a differential diagnosis. 

So what is warm AIHA? How is it diagnosed? How not to mistake it for another disease?

We explain it all in our article!

Warm autoimmune haemolytic anaemia (wAIHA): symptoms, diagnosis and similarities with other conditions

What is warm autoimmune haemolytic anaemia? 

Warm AIHA is a blood disease, a special form of autoimmune haemolytic anaemia. It is characterised by the presence of antibodies in the blood that target red blood cells when the body temperature is between 37°C and 40°C. Warm AIHA accounts for 60-70% of cases of autoimmune haemolytic anaemia. The yearly incidence of wAIHA in North America and Western Europe is estimated to be between 1/80,000 and 1/35,000. 

Warm AIHA is more frequently found in women than in men: approximately two women are affected for every male patient in the adult population. 

Warm AIHA affects red blood cells, which are responsible for transporting oxygen throughout the body. The destruction of blood cells is called anaemia. Various symptoms are caused by this lack of oxygen: shortness of breath, fatigue, etc. Symptoms linked to the destruction of the red blood cells themselves may also appear: jaundice (yellow colouring of the skin and mucous membranes), splenomegaly (increased volume of the spleen), etc.

There are different types of warm AIHA: half of the cases are idiopathic (the cause of the development of the disease is not known); the other half are linked to the presence of another condition, most often chronic lymphocytic leukaemia (CLL) or another autoimmune or inflammatory disease such as systemic lupus erythematosus.

>> To learn more about warm autoimmune haemolytic anaemia, its symptoms and treatments, click here to access the condition's fact sheet! <<

How is warm autoimmune haemolytic anaemia diagnosed?  

The diagnosis of warm AIHA is established after various examinations, including: 

  • A clinical examination during which the doctor looks for symptoms that help suggest the disease: sudden or progressive onset of fever, chills, back pain, jaundice, dark-red urine, associated with signs of anaemia, such as tachycardia (accelerated heart rate), pallor and shortness of breath, particularly during physical effort. The doctor may also discover splenomegaly (enlarged spleen) when palpating the patient's abdomen. 
  • A blood test called a haemogram, or complete blood count (CBC), in which certain blood parameters are modified: haemoglobin (red blood cells) levels are reduced, which indicates the presence of anaemia. This anaemia is described as normocytic, normochromic (the average size of red blood cells is unchanged) and regenerative (the number of reticulocytes is unchanged);
  • Examination of a drop of blood under a microscope, otherwise known as a blood smear: this examination provides qualitative information about blood composition. In warm AIHA, this test will show polychromatophilia, which means variation in red cell colouring, anisocytosis, which means variation in the size of red blood cells, and poikilocytosis, which means variation in the shape of red blood cells. It is also possible to detect schistocytes, fragments of destructed red blood cells, which means that red blood cells are under attack;
  • Other blood tests can confirm haemolysis: increased free bilirubin (an element released in the blood during the destruction of red blood cells) and LDH (an enzyme found in many tissues, its blood level is generally low) levels, and decreased level of haptoglobin (protein in charge of managing the haemoglobin released in the blood during the breakdown of red blood cells; when its level decreases, it is the sign of a massive destruction of red blood cells, and thus a sign of haemolysis);
  • The Coombs test allows to demonstrate the presence of antibodies targeting the red blood cells.

In order to establish the diagnosis, the doctor generally carries out a differential diagnosis: a method of differentiating a disease from other conditions that have similar symptoms or characteristics.   

What other conditions should be considered during the differential diagnosis of warm autoimmune haemolytic anaemia? 

Warm autoimmune haemolytic anaemia is mainly differentiated from cold autoimmune haemolytic anaemia. It should also be differentiated from other causes of haemolytic anaemia.

The main difference with warm AIHA is the temperature at which the antibodies react: i.e. in CAD (cold agglutinin disease) the antibodies react when the body temperature is < 37°C, in contrast to warm AIHA in which the antibodies become active when the body temperature is above 37°C

The Coombs test can be used to differentiate the type of AIHA. In the case of warm AIHA, the antibodies are immunoglobulin type G; the presence of complement C3 can also be detected. In the case of CAD, the autoantibodies are generally of type M. Complement C3 can also be detected. 

The temperature at which the Coombs test is performed is also important to consider when establishing a diagnosis of either condition.

The presence of an underlying disease may also be a factor in the diagnosis of warm or cold AIHA.

Other causes of haemolytic anaemia

Other conditions, such as hereditary spherocytosis (or Minkowski-Chauffard syndrome), which causes membrane abnormalities in red blood cells, can also lead to the development of haemolytic anaemia. In these cases, haemolysis is chronic and not influenced by body temperature. 

Abnormalities in haemoglobin (the protein responsible for oxygen transportation in red blood cells) can also cause haemolytic anaemia. These are usually hereditary diseases. 

Haemolytic anaemia can also be caused by enzyme abnormalities, a decrease in the level of an enzyme, e.g. G6PD, which can cause moderate chronic haemolysis with haemolytic episodes triggered by drugs or infections. 

Knowing how many conditions can lead to haemolytic anaemia, it is essential to make a differential diagnosis in order to identify the exact cause and to be able to treat it as well as possible.


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avatar Alizé Vives

Author: Alizé Vives, Pharmacist, Data Scientist

Alizé holds a PharmD and a master's degree in strategy and international business from ESSEC Business School in France. She has several years of experience working with patients and members, conducting surveys for... >> Learn more

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