Powered By
Rare diseases can be difficult to count, and warm autoimmune hemolytic anemia (warm AIHA or wAIHA) is no exception. Because relatively few people have the condition, researchers can’t always pin down exactly how common it is or who is most likely to develop it.
Still, studies have found some patterns related to age, biological sex, and certain health conditions.
This article will explain who is more likely to develop warm AIHA, which health conditions are associated with it, and what researchers know about genetics and other risk factors.
Sign up to view the results!
Continue with Facebook
Continue with Email
Age and biological sex appear to matter most, while the evidence around race and ethnicity is much less clear. Health conditions can also affect risk.
About half of warm AIHA cases are linked to another medical condition or trigger, while the other half have no identifiable underlying cause.
Age is one of the clearest patterns researchers have found. Warm AIHA can develop at any age, but it’s more common later in life. A 2021 review of 27 studies involving more than 4,000 people with wAIHA found a median age at diagnosis of 68.7 years.
Another study reported a substantially higher incidence among adults over 50 than among younger adults.
While children can develop warm AIHA, it’s much less common in them than in adults. Researchers don’t have a reliable estimate of what percentage of all childhood AIHA cases are wAIHA.
Other types of AIHA show a stronger link to childhood. For example, paroxysmal cold hemoglobinuria (PCH) occurs mainly in children, often after an infection.
Warm AIHA appears to be more common in women. In the 2021 systematic review, 66 percent of the people with wAIHA were female.
However, the pattern wasn’t the same at every age. The researchers found a large female predominance among adults but a male predominance among children. This means the association between biological sex and wAIHA may differ between adult and pediatric cases.
Researchers haven’t established why women make up a larger share of adults with wAIHA. One possible factor is that other autoimmune disorders commonly associated with wAIHA, like systemic lupus erythematosus (SLE), or lupus, are also more common in women.
There isn’t enough evidence to say that wAIHA is more common in one racial or ethnic group. The large systematic review of wAIHA epidemiology examined age, sex, and underlying health conditions but didn’t analyze differences in wAIHA risk by race or ethnicity.
Some studies may describe the racial or ethnic makeup of the people they included. However, that information alone can’t show whether one group has a higher risk. Factors such as where a study took place and who receives care at that medical center can affect which groups are represented.
For now, age, biological sex, and certain underlying health conditions are better-established factors associated with wAIHA.
In warm AIHA, the immune system produces autoantibodies, which are antibodies that mistakenly target the body’s own red blood cells. The autoantibodies involved in wAIHA are usually a type called immunoglobulin G (IgG).
These antibodies bind most strongly to red blood cells at normal body temperature, which is why the condition is called warm AIHA.
AIHA doctors generally describe warm AIHA as either primary or secondary. Primary means no underlying cause has been identified. Secondary warm AIHA occurs along with another health condition or an identifiable trigger.
The distinction is fairly evenly divided. The 2021 systematic review found that about 49 percent of wAIHA cases were secondary. However, estimates can vary depending on the population studied and how extensively doctors look for an underlying cause.
Autoimmune diseases are an important cause of secondary wAIHA. In an autoimmune condition, the immune system mistakenly reacts against the body’s own cells or tissues.
Lupus was the most commonly reported underlying condition in the 2021 review. Warm AIHA has also been associated with other autoimmune conditions, including Sjögren’s disease, autoimmune hepatitis, and rheumatoid arthritis.
An American Society of Hematology review estimated that about one-quarter of people with wAIHA have an identifiable immune or autoimmune disorder.
However, having an autoimmune disease doesn’t mean you’ll develop wAIHA. It’s only one thing doctors may consider when looking for an underlying cause.
Certain blood cancers are linked to secondary wAIHA, particularly cancers that affect lymphocytes, a type of white blood cell.
These include chronic lymphocytic leukemia (CLL), non-Hodgkin B-cell lymphoma, angioimmunoblastic T-cell lymphoma, and large granular lymphocytic leukemia. Warm AIHA is reported in 7 percent to 10 percent of people with CLL.
Warm AIHA has also been reported in people with some conditions that affect immune system function. These include inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis.
Other immune system disorders linked to AIHA include common variable immunodeficiency (CVID) and autoimmune lymphoproliferative syndrome (ALPS). These conditions can disrupt how the immune system develops or regulates itself, which may make autoimmune blood cell problems more likely.
These links may be especially important in children or in people whose AIHA keeps coming back or affects more than one type of blood cell — a condition known as Evans syndrome. In those situations, doctors may consider testing for an underlying immune system disorder.
Viral or bacterial infections may disrupt the immune system in ways that cause it to react mistakenly against red blood cells.
Viruses linked to AIHA include Epstein-Barr virus (EBV), cytomegalovirus (CMV), hepatitis viruses, HIV, and SARS-CoV-2.
One myAIHAteam member reported being diagnosed with AIHA two months after COVID-19 infection.
COVID-19 is a more recently recognized possible trigger of AIHA. A 2024 study identified 37 reported cases of newly diagnosed AIHA in adults after COVID-19 infection. Of those, 19 were wAIHA.
Bacterial and parasitic infections have also been associated with AIHA. These include tuberculosis, brucellosis, and babesiosis.
As with immune system disorders, infection-associated wAIHA may be especially relevant in children. One study reported that infections are among the most commonly reported causes of secondary AIHA in children.
Some medications can also cause the immune system to destroy red blood cells, a process called hemolysis. This is called drug-induced immune hemolytic anemia. Some cases can closely resemble wAIHA.
Medications associated with this reaction include methyldopa (used to treat high blood pressure) and some penicillin and cephalosporin antibiotics.
AIHA can also develop after an organ or stem cell transplant. Posttransplant AIHA is a known form of secondary AIHA, although it’s much less common than causes such as an autoimmune disease or an underlying blood cancer.
Warm AIHA isn’t considered to be an inherited disease. In other words, it typically isn’t passed directly from parent to child through a single gene.
However, researchers have found genetic differences that may be associated with the likelihood of developing AIHA.
These findings don’t mean there’s a genetic test that can predict whether someone will develop wAIHA. Research suggests genetics may be one part of a more complicated picture involving the immune system, underlying health conditions, and other environmental triggers.
Risk factors show patterns across groups of people. They can’t predict with certainty who will develop wAIHA. Some people develop it without an identifiable underlying disease, while many people with conditions linked to wAIHA never develop it.
If you’ve received a wAIHA diagnosis, your healthcare team may try to determine whether it’s primary or secondary. Doctors may look for autoimmune diseases, blood cancers, immune disorders, infections, medication triggers, and other possible causes.
Sometimes, no underlying cause can be found. Understanding what is, or isn’t, associated with your wAIHA can help your healthcare team decide what follow-up or treatment may be appropriate.
Get updates directly to your inbox.
Continue with Facebook
Continue with Email
Continue with Facebook
Continue with Email
Become a member to get even more
Join
Your Privacy Choices
This is a member-feature!
Sign up for free to view article comments.
We'd love to hear from you! Please share your name and email to post and read comments.
You'll also get the latest articles directly to your inbox.