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Viral infections and Autoimmune Hemolytic Anemia

Hemolytic anemia

Autoimmune hemolytic anemia is a blood disorder that is characterized by the production of antibodies by the immune system of the body which attack and destroy red blood cells in the bloodstream.1

In just over half the cases of this disorder, the cause is unknown and referred to as idiopathic autoimmune hemolytic anemia. In the other just under 50 percent of cases, there are certain risk factors associated with the development of the condition and these are termed secondary causes of autoimmune hemolytic anemia.

Secondary autoimmune hemolytic anemia can then be further classified into the warm and cold types of the disease. The warm type is the more common of the two but also the less severe condition. It causes less problematic signs and symptoms and is easier to manage than the cold type.

Warm type autoimmune hemolytic anemia seems to be associated with conditions such chronic lymphocytic leukemia and lymphoma, as well as other autoimmune conditions such as lupus, rheumatoid arthritis, and celiac disease. The cold type can be triggered by exposure to cold temperatures.

Viral infections are known to be secondary causes of both the warm and cold types of this condition.

Viral infections associated with the blood disorder

The following viruses are associated with the development of warm type autoimmune hemolytic anemia:

  • Hepatitis A or E
  • Epstein-Barr virus (EBV)
  • Cytomegalovirus (CMV)
  • Human parvovirus B19

The mechanism of how these viruses trigger the immune system into producing red blood cell antibodies may involve activation of the B-cells of the immune system in response to these infections.2

Another thought around how viruses may cause this problem is through reactivation of the herpesviruses such as EBV and CMV, although secondary autoimmune hemolytic anemia is mainly linked to primary viral infections. The hypothesis behind the reactivation theory is that the latent herpesviruses can alter the way the immune system responds to repeat infections caused by these organisms. Also, it seems that these viruses can actually worsen the health status of patients diagnosed with the blood disorder.2

Another theory associating the development of autoimmune hemolytic anemia due to reactivation of latent herpesviruses is through the administration of vaccines. However, this is purely a theory and there are no known or reported cases where autoimmune hemolytic anemia was caused by vaccine administration.

Influenza and autoimmune hemolytic anemia

There has also been a growing concern regarding the possibility of developing autoimmune hemolytic anemia secondary to the presence of an influenza virus infection or the administration of an influenza vaccine. The development of the blood disorder secondary to an influenza infection was reported in three cases from the English literature and one case from the Japanese literature. In one of the cases, the child who developed autoimmune hemolytic anemia after contracting the influenza virus was already known to have acute lymphoblastic leukemia, so this may have been the actual trigger for the blood disorder rather than the influenza virus.3

In the other three cases, two of the patients were elderly individuals with other chronic conditions which increased their morbidity and mortality risk, but there was a case of a 19-year old girl who developed the hemolytic anemia after contracting the influenza virus. She didn’t have any other co-morbidities but the influenza virus she contracted was the H3N2 mutation, otherwise known as ‘bird-flu’, which is associated with increased complications due to its resistance against the body’s immune system.

Some of these patients also received the anti-viral medication oseltamivir because they were infected with either the mentioned H3N2 influenza mutation or the H1N1 (swine flu) variant. For this reason, drug-induced autoimmune hemolytic anemia could also not be excluded as a possible differential diagnosis of the virus-induced blood disorder. In one case, oseltamivir was the cause of the hemolytic anemia and the patient recovered around two weeks after the drug was discontinued.3


Influenza virus infections may cause autoimmune hemolytic anemia in few cases and these patients may go into spontaneous remission once the viral infection has resolved.

It’s important to mention though that secondary autoimmune hemolytic anemia may be a fatal primary illness in patients who develop influenza infections if they are in poor health at the time of diagnosis.