Autoimmune Hemolytic Anemia: Symptoms, Causes, and More

Autoimmune hemolytic anemia (AIHA) is a blood disorder that occurs when your body’s immune system mistakes your red blood cells as a threat and creates antibodies to destroy them. Red blood cells are responsible for carrying oxygen throughout the body. When antibodies destroy red blood cells faster than your body can replace them, your body’s tissues do not get enough oxygen, which can cause symptoms like fatigue, weakness, and headaches.

AIHA is rare and affects one to three individuals per 100,000 people each year. While the exact cause of AIHA is currently unknown, sometimes infections, medications, or underlying autoimmune diseases can trigger the condition. Treatment for AIHA typically involves medications to suppress the immune system and blood transfusions to replenish lost red blood cells when AIHA symptoms are severe.

There are two types of autoimmune hemolytic anemia (AIHA), which healthcare providers classify based on the temperature at which the immune system attacks red blood cells. This distinction is important because each AIHA type requires different treatment approaches.

Warm Autoimmune Hemolytic Anemia

Warm autoimmune hemolytic anemia (w-AIHA) is the more common type, accounting for roughly 70-80% of adult cases and 50% of pediatric cases of AIHA. With this type, the immune system antibodies that attach to and attack red blood cells activate at an average body temperature, leading to anemia.

Cold Autoimmune Hemolytic Anemia

Cold autoimmune hemolytic anemia (c-AIHA), or cold agglutinin disease (CAD), most commonly affects adults between 40 and 80 years old. With CAD, antibodies activate at cooler temperatures and attach to red blood cells before destroying them. Exposure to cold temperatures activates the antibodies, causing red blood cells to clump together and become destroyed.

Primary and Secondary Autoimmune Hemolytic Anemia

Healthcare providers sometimes also classify AIHA based on the underlying cause of the condition:

Primary AIHA: About 50% of AIHA cases are primary or idiopathic, meaning there is no identifiable underlying cause.
Secondary AIHA: Secondary AIHA develops in response to an underlying condition, such as an autoimmune disorder, cancer, infection, or certain medications.

Autoimmune hemolytic anemia symptoms vary, depending on the severity of the condition. Red blood cells contain hemoglobin—a protein that helps deliver oxygen to the body’s tissues. Hemolytic anemia develops when the body does not have enough red blood cells to deliver oxygen-rich blood to its tissues.

Symptoms of AIHA tend to develop gradually and may include:

As the body continues to lose red blood cells more quickly than it can replace them, symptoms may worsen, and new ones can develop, including:

Severe, untreated AIHA can also cause:

When you don’t have AIHA, the immune system protects against foreign invaders (e.g., bacteria, viruses) that can cause infections. However, with AIHA, the immune system mistakenly identifies healthy red blood cells as threatening and produces antibodies to destroy them.

Typically, red blood cells live for approximately 120 days before the spleen filters and removes them from the bloodstream. With AIHA, antibodies destroy the red blood cells prematurely (before it’s time) and more quickly than the body can replace them, leading to a shortage of red blood cells in your body.

What causes this abnormal immune response is unknown for primary AIHA. However, several factors can trigger the development of secondary AIHA, including:

Infections: Viral and bacterial infections, including influenza (the flu), certain types of pneumonia, tuberculosis, and Epstein-Barr virus (EBV)
Medications: Certain medications, including non-steroidal anti-inflammatory drugs (NSAIDs), chemotherapy drugs, antivirals, and antibiotics, can stimulate the production of red blood cell-destroying antibodies
Autoimmune conditions: Systemic lupus erythematosus (lupus), Sjögren’s syndrome (SS), systemic sclerosis (SSc), and rheumatoid arthritis (RA)
Immunodeficiency (weakened immune system): Bone marrow or organ transplantation can affect your immune system health
Certain cancers: Lymphoma, chronic lymphocytic leukemia, and ovarian and prostate cancers.

Risk Factors

Anyone can develop AIHA, but certain risk factors can increase the likelihood of developing the condition. These risk factors include:

Age: AIHA is most common in older adults 50- 80 years old.
Sex: This blood disorder is slightly more common in people assigned female at birth.
Underlying health conditions: Living with an autoimmune disorder, blood cancer, and a weak immune system can increase the risk of AIHA.

To diagnose autoimmune hemolytic anemia, your healthcare provider will review your medical history, ask about your symptoms, and perform a physical examination. They will also order a series of diagnostic blood tests to assess red blood cell (RBC) health, identify the presence of hemolytic (RBC-destroying) antibodies, and rule out other possible causes of anemia.

Blood tests for diagnosing AIHA include:

Complete blood count (CBC): Measures the levels of various blood cells, including red and white blood cells, platelets, and hemoglobin in the blood
Reticulocyte count: Assesses the number of young red blood cells (called reticulocytes) in the blood to determine whether your bone marrow replaces lost RBCs quickly enough
Peripheral blood smear: Involves examining the shape and size of red blood cells under a microscope to identify abnormal cells; sphere-shaped RBCs can help confirm a diagnosis of autoimmune hemolytic anemia
Coombs test: Detects the presence of RBC-destroying antibodies attached to red blood cells or in the bloodstream to confirm a diagnosis of autoimmune hemolytic anemia
Lactate dehydrogenase (LDH) test: Checks the level of LDH, an enzyme RBCs release when they are destroyed
Haptoglobin test: Inspects levels of haptoglobin in the blood, which decrease when red blood cells are broken down or antibodies prematurely destroy them.
Bilirubin test: Examines bilirubin levels, a byproduct of red blood cell breakdown in the body that may be elevated with hemolytic anemia

Agluttinins test: Looks for the presence of agglutinins, antibodies that cause red blood cells to clump together, to help diagnose cold AIHA

If you are diagnosed with autoimmune hemolytic anemia, the primary goal of treatment is to suppress the immune system’s attack on red blood cells to reduce anemia symptoms. Treatment approaches vary depending on the severity of the condition and the type of AIHA (warm or cold) you have.

Medications

Corticosteroid medications, such as Rayos (prednisone), are the first-line treatment for managing AIHA. This medication helps suppress the abnormal immune response to slow or stop the early destruction of red blood cells. Corticosteroid treatment helps improve symptoms within two to three weeks for 80% of people with AIHA.

If you do not notice improvements in your symptoms within three weeks, your healthcare provider may prescribe Rituxan (rituximab), a monoclonal antibody, to help reduce AIHA symptoms.

Splenectomy

When medications are ineffective, or you have severe warm-AIHA, your healthcare provider may recommend a splenectomy—the surgical removal of the spleen. The spleen filters blood cells and is often the primary site of red blood cell destruction with AIHA. Removing the spleen helps reduce symptoms in up to 90% of people with warm AIHA who undergo the surgery.

Blood Transfusions

If you have severe AIHA, your healthcare provider may recommend blood transfusions to replenish your body’s supply of red blood cells and improve oxygen delivery to your body’s tissues. Some people with severe AIHA require frequent blood transfusions to help manage symptoms.

Lifestyle Adjustments

Your healthcare provider may also recommend other suggestions to keep you comfortable, such as:

Avoid cold temperatures: If you have cold AIHA, your healthcare provider may recommend avoiding exposure to cold temperatures or swimming in cold bodies of water to help prevent the onset of symptoms. If you live in a naturally cold climate, wearing extra layers to keep yourself warm can help.
Take folic acid supplements: Folic acid (also known as folate) supplements help support red blood cell production and lower the risk of severe anemia symptoms. Your provider will often recommend these supplements alongside other medications you’re taking.

Because there are so many potential triggers, it is not always possible to prevent autoimmune hemolytic anemia. However, if you have an AIHA diagnosis, there are steps you can take to reduce the frequency and severity of symptoms:

Manage underlying conditions: If your AIHA is associated with another medical condition, such as an autoimmune disease, following your treatment plan may help lower the risk of AIHA symptom flares (periods where symptoms are most active).
Avoid infections: Practice good hygiene, stay current on your vaccines, and avoid contact with people with bacterial or viral infections to lower your risk of getting sick.
Minimize exposure to cold: If you have cold AIHA, avoiding cold environments and dressing warmly in cold weather can help prevent red blood cell destruction.

Autoimmune hemolytic anemia can lead to complications, which may develop in response to low red blood cell counts or treatments. These complications include:

Splenomegaly: Enlargement of the spleen due to the rapid destruction of red blood cells can cause abdominal pain and increase the risk of spleen rupture.
Infections: Taking immunosuppressant medications to treat AIHA or undergoing a splenectomy (spleen removal surgery) can weaken the immune system and increase the risk of developing viral and bacterial infections.
Thrombosis: The abnormal destruction of red blood cells increases the risk of blood clots forming in veins or arteries (known as thrombosis). These clots can reduce or block normal blood flow and increase the risk of heart attack or pulmonary embolism (blood clot in the lung).
Cutaneous ulcerations: In cold AIHA, reduced blood flow after cold exposure causes red blood cells to clump together, increasing the risk of skin ulcers or tissue death (known as necrosis) in the extremities, like your fingers and toes.
Kidney dysfunction: The breakdown products of destroyed red blood cells can overload the kidneys, leading to potential kidney problems.

Autoimmune hemolytic anemia (AIHA) is a rare disorder that causes your immune system to attack healthy red blood cells (RBCs) by accident. This can lead to anemia, causing symptoms like fatigue, shortness of breath, and lightheadedness.

The exact cause of AIHA is unknown, but certain infections, medications, and health conditions can trigger its development. Treatments like medications and procedures can help manage symptoms and improve quality of life.