Reviewed By: Pramod Kerkar, MD, FFARCSI

What is Cold Agglutinin Disease?

Cold agglutinin disease is a rare medical condition where the body's own immune system mistakenly destroys its own RBCs or red blood cells (autoimmune hemolytic anemia) when exposed to cold temperature. In cold agglutinin disease, when the patient’s blood gets exposed to cold, then certain proteins, which under normal circumstances destroy bacteria, get attached to red blood cells resulting in clumping of the RBCs (agglutination). This leads to premature destruction of the red blood cells (hemolysis) causing anemia and other related symptoms in the patient.

Cold agglutinin disease can occur as a primary condition, which has no known cause; or it can be secondary, which means occurring as a result of some underlying conditions like another autoimmune disease, infection or certain cancers. Treatment for cold agglutinin disease depends on various factors, such as the severity of the disease, presenting symptoms of the patient and the underlying cause of this condition.

What are the Other Names of Cold Agglutinin Disease?

Cold Agglutinin Disease is also referred to as Cold Antibody Disease and Cold Antibody Hemolytic Anemia.

What is the Cause of Cold Agglutinin Disease?

Primary cold agglutinin disease has no known cause. Whereas, secondary cold agglutinin disease is caused by some other underlying medical conditions such as:

  • Cold Agglutinin Disease Caused By Bacterial Infections like syphilis, mycoplasma, listeriosis, Legionnaires' disease or E. Coli
  • Cold Agglutinin Disease Caused By Viral Infections such as cytomegalovirus, Epstein-Barr virus, mumps, rubella, varicella, adenovirus, influenza, hepatitis C or HIV.
  • Cold Agglutinin Disease Caused By Other Autoimmune Diseases like systemic lupus erythematosus (SLE)
  • Cold Agglutinin Disease Caused By Parasitic Infections like trypanosomiasis or malaria.
  • Cold Agglutinin Disease Caused By Cancers such as chronic lymphocytic leukemia, lymphoma, Waldenström macroglobulinemia, Kaposi sarcoma and multiple myeloma.

Is Cold Agglutinin Disease a Hereditary Condition?

Cold agglutinin disease is not a hereditary condition. As of now, there has been no report of cold agglutinin disease being a hereditary or genetic condition.

Cold agglutinin disease is classified as primary with no known cause; or secondary which is caused by some other condition. In some patients, there are multiple factors which can cause cold agglutinin disease, which means that genes and environmental factors can make person more vulnerable to developing this condition.

Who is at Risk for Cold Agglutinin Disease?

Middle aged adults are more commonly affected with cold agglutinin disease. Women are more vulnerable to suffering from cold agglutinin disease. Other than this, individuals suffering from lymphoproliferative diseases, infectious mononucleosis or mycoplasma pneumonia are at increased risk for having cold agglutinin disease.

What are the Symptoms of Cold Agglutinin Disease?

Cold temperatures or viral infection aggravates the symptoms of cold agglutinin disease; which means that symptoms worsen in winter season. The development of symptoms of cold agglutinin disease can be gradual or sudden in onset.

Symptoms of Anemia in Cold Agglutinin Disease: Common symptoms of cold agglutinin disease consist of hemolytic anemia where there is destruction of RBCs leading to decreased levels of red blood cells. Other symptoms and their severity depend on the severity of the anemia present in cold agglutinin disease and can consist of: Dizziness, fatigue, headaches, pallor, cold hands and feet, dark colored urine, muscle weakness, pain in the chest, jaundice, joint pain, diarrhea or vomiting, back pain or leg pain.

Heart Symptoms in Cold Agglutinin Disease: Patient can also have heart problems such as arrhythmia, an enlarged heart, heart murmur or even heart failure. Heart problems due to cold agglutinin disease occur because the heart has to pump blood twice as hard to ensure that the whole body gets enough healthy red blood cells.

Temperature Symptoms in Cold Agglutinin Disease: Patients suffering from cold agglutinin disease can also have bluish coloration and pain in the hands and feet or Raynaud's disease. These symptoms of cold agglutinin disease occur due to poor or slow blood circulation.

Additional Symptoms Of Cold Agglutinin Disease consist of spleen enlargement and livedo reticularis where the patient has mottled discoloration of the skin.

Symptoms of Secondary Cold Agglutinin Disease:

Patients having secondary cold agglutinin disease, which occurs as a result of some underlying disease, will have signs and symptoms of that condition such as:

  • Mycoplasma pneumoniae infection is the commonest cause of cold agglutinin disease and can produce respiratory symptoms in the patient.
  • Cold agglutinin disease occurring as a result of cancers or infections can have swollen or enlarged lymph nodes.

How is Cold Agglutinin Disease Diagnosed?

Different types of tests need to be done for diagnosing cold agglutinin disease. This condition is initially suspected when abnormal clumping of RBCs is detected on a complete blood count. Most of the times, cold agglutinin disease is diagnosed on the evidence of hemolytic anemia seen via blood tests or symptoms experienced by the patient. Other signs of cold agglutinin disease, such as liver or spleen enlargement can also help with the diagnosis. Coombs test can be done to detect the presence of a specific type of antibody (IgM) which helps in diagnosing cold agglutinin disease.

How is Cold Agglutinin Disease Treated?

Treatment of cold agglutinin disease depends on various factors, such as severity of the disease, the symptoms and the underlying cause of this condition. Treatment of patients having secondary cold agglutinin disease is diagnosing and treating the underlying cause. Patient with mild symptoms of cold agglutinin disease, such as mild anemia, may not need any specific treatment and can be managed by avoiding exposure to cold temperature.

Medicines for Treating Cold Agglutinin Disease

Medical treatment in severe cases of hemolysis occurring in cold agglutinin disease consists of prescribing the medication Rituximab. This is an antibody which selectively decreases the specific forms of immune cells and is effective in about half of the patients suffering from severe cold agglutinin disease. Treatment with Rituximab needs to be done for about a month or two and the effect of this treatment last for a couple of years after which it can be used again in case of relapse. Rituximab can be combined with another medicine, fludarabine, for more efficacy; however, the side effects of this combination treatment are more serious and should be used only if Rituximab is not working on its own.

Plasmapheresis for Treating Cold Agglutinin Disease

Finally, cold agglutinin disease can be treated with plasmapheresis, where the patient’s blood is filtered to extract antibodies. This procedure is beneficial in patients suffering from acute hemolytic crisis and before any surgery which needs hypothermia is done. The effect of plasmapheresis in cold agglutinin disease is short term.

There are several studies still going on for more effective treatment of cold agglutinin disease.

What is the Prognosis of Cold Agglutinin Disease?

The prognosis of patients suffering from Cold Agglutinin Disease depends on various factors, such as severity of the disease, its underlying cause and the symptoms experienced by the patient. The prognosis is very good in patients having cold agglutinin disease that is caused by viral or bacterial infections. The prognosis is also good in case of mild to moderate primary cold agglutinin disease provided that the patient avoids excessive exposure to cold temperature. The prognosis is poor for patients having cold agglutinin disease caused by cancers or HIV infection.

Also Read:

Pramod Kerkar

Written, Edited or Reviewed By:

, MD,FFARCSI

Pain Assist Inc.

Last Modified On: March 26, 2018

This article does not provide medical advice. See disclaimer

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