Causes of autoimmune hemolytic anemia
Causes of autoimmune hemolytic anemia Autoimmune hemolytic anemia (AIHA) is a condition in which the immune system mistakenly targets and destroys the body’s own red blood cells, leading to anemia. Understanding the causes behind AIHA is crucial for diagnosis and effective management, as it often involves a complex interplay of genetic, environmental, and immune factors. While in many cases the exact trigger remains unidentified, several key factors have been associated with the development of autoimmune hemolytic anemia.
One of the primary causes of AIHA is an abnormal immune response. In a healthy individual, the immune system distinguishes between self and non-self entities, attacking pathogens like bacteria and viruses while sparing the body’s own cells. However, in autoimmune conditions like AIHA, this self-tolerance is disrupted. The immune system produces antibodies—primarily of the IgG or IgM class—that mistakenly recognize red blood cell surface proteins as foreign. These autoantibodies bind to red blood cells, marking them for destruction either within the spleen or via complement activation in the bloodstream.
The development of autoimmune hemolytic anemia can be idiopathic, meaning no identifiable cause is found. However, it is often associated with other underlying medical conditions. For instance, autoimmune diseases such as systemic lupus erythematosus (SLE) are well-known to cause secondary AIHA. In these cases, the immune dysregulation characteristic of the autoimmune disorder extends to include red blood cell destruction. Similarly, other autoimmune conditions like rheumatoid arthritis or autoimmune thyroid diseases may also be linked to AIHA, reflecting a broader immune imbalance.
Infections represent another significant factor in the development of AIHA. Certain viral infections, including Epstein-Barr virus (EBV), cytomegalovirus (CMV), and hepatitis viruses, have been implicated as triggers. These infections can stimulate the immune system in a way that leads to the production of cross-reactive antibodies—antibodies that, while targeting the infectious agent, also
recognize and attack red blood cells due to molecular similarities, a phenomenon known as molecular mimicry. Bacterial infections, such as syphilis or Mycoplasma pneumoniae, have also been associated with AIHA, often causing a transient form of hemolytic anemia.
Drug-induced AIHA is another notable cause. Certain medications can alter red blood cell surfaces or stimulate autoantibody production, leading to hemolysis. Drugs like penicillin, cephalosporins, methyldopa, and some non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to induce autoimmune hemolytic anemia. The mechanism may involve the drug binding to red blood cell membranes and creating new antigenic determinants, which then provoke an immune response.
Genetic predisposition also plays a role in some cases. Although AIHA is not solely inherited, individuals with certain genetic backgrounds may have a higher susceptibility to immune dysregulation. Factors like HLA gene variants and immune regulatory gene polymorphisms can influence how the immune system functions and its tendency to develop autoimmunity.
In summary, autoimmune hemolytic anemia arises from a multifaceted interplay of immune dysregulation, underlying autoimmune or infectious diseases, medication exposure, and genetic predispositions. Recognizing these causes helps clinicians tailor treatment strategies and anticipate potential complications, ultimately improving patient outcomes.
