Autoimmune hemolytic anemia (AIHA) occurs when your immune system mistakenly attacks and destroys red blood cells, leading to anemia (low levels of red blood cells). Several other autoimmune system disorders are associated with AIHA, including Evans syndrome. In Evans syndrome — which affects about 7 percent of people with AIHA — a person’s immune system attacks multiple types of blood cells at once.

In this article, we’ll explore some of the similarities and differences between Evans syndrome and AIHA.

What Is Evans Syndrome?

Like AIHA, Evans syndrome occurs because of an abnormal immune system reaction. Your immune system makes proteins called antibodies that normally help find and kill germs such as bacteria and viruses.

In the case of AIHA, your immune system makes antibodies that mistakenly attack your red blood cells, causing levels of these cells to drop. Red blood cells are responsible for carrying oxygen around your body.

In Evans syndrome, antibodies target red blood cells and other types of cells, including platelets and white blood cells. Platelets are cell fragments that help your blood form clots when you are injured. White blood cells help fight infections and get rid of old or damaged cells.

Most people with Evans syndrome have idiopathic thrombocytopenia purpura (ITP), a condition in which the immune system attacks platelets. Sometimes, people with Evans syndrome also have neutropenia, a condition in which certain types of white blood cells called neutrophils are also destroyed. Neutrophils help the body fight off infections.

In other words, people with Evans syndrome have AIHA in addition to ITP and/or neutropenia.

Do Symptoms of AIHA and Evans Syndrome Overlap?

In general, both people with AIHA and those with Evans syndrome have anemia, a condition caused by low red blood cells. Anemia symptoms include:

• Tiredness
• Difficulty taking a deep breath
• Rapid heart rate
• Pale skin
• Dark urine
• Back pain
• Cold hands and feet
• Jaundice (yellow-appearing skin and whites of the eyes)

Those with Evans syndrome may also have symptoms based on which other types of blood cells are being destroyed. People with ITP have low platelet levels, leading to:

• Petechiae (tiny red or purple dots on the skin)
• Purpura (a rash made up of flat, purple spots)
• Frequent bruising
• Excessive bleeding, such as more than expected with a small injury
• Other bleeding problems, such as bleeding gums, a bloody nose, or heavy menstrual periods

When neutropenia occurs as a part of Evans syndrome, low white blood cell levels can cause frequent infections, mouth sores, fever, or malaise (generally feeling sick).

Anemia, ITP, and neutropenia don’t always occur together during Evans syndrome. The different sets of symptoms may not appear at the same time — you may have ITP symptoms initially and develop signs of anemia later. Symptoms may also come and go as a result of treatment.

What Causes AIHA and Evans Syndrome?

Health experts aren’t always sure what prompts the body to make the abnormal antibodies that lead to these two conditions. In about half of AIHA cases and most cases of Evans syndrome, doctors can’t determine the reason the condition developed.

AIHA is often caused by other health conditions. These may include:

• Rheumatoid arthritis
• Systemic lupus erythematosus (SLE, also commonly called lupus)
• Sjögren’s syndrome
• Thyroid conditions
• Ulcerative colitis
• Viral infections

Taking certain medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, and cancer drugs, can also lead to AIHA. Undergoing a blood transfusion may also increase risk.

It’s not always clear why some people develop Evans syndrome. Some cases are connected to the same conditions that cause AIHA, such as lupus and Sjögren’s syndrome. Evans syndrome may also occur alongside another blood disorder, like lymphoma, leukemia, or autoimmune lymphoproliferative syndrome.

Who Is Most at Risk for AIHA and Evans Syndrome?

Scientists haven’t yet identified risk factors that may lead to these conditions. However, both AIHA and Evans syndrome, like other autoimmune disorders, develop more frequently in women.

Both conditions can occur in people of all ages but are more common in middle-aged adults. People over 40 most often get AIHA, and the average age at diagnosis for those with Evans syndrome is 55.

Diagnosing AIHA and Evans Syndrome

No one test can confirm Evans syndrome. Doctors identify this condition by ruling out others that might lead to similar problems with blood cells.

Because people with Evans syndrome also generally have AIHA, doctors typically use the same tests to help diagnose both conditions. People with Evans syndrome may also need to undergo additional tests to determine what’s causing drops in platelet or white blood cell levels.

Tests To Look for Blood Cell Changes

The first step in diagnosing AIHA or Evans syndrome is usually to confirm that you have cytopenia (low levels of one or more types of blood cells).

The complete blood count (CBC) is an important part of the diagnosis. This test measures levels of red blood cells, platelets, and different types of white blood cells. Your doctor may use a CBC to help diagnose anemia, ITP, or neutropenia.

A peripheral blood smear is a test in which a drop of your blood is studied under a microscope to look for changes in the appearance of your cells. Red blood cells are usually round with an indentation in the middle, and the cells found in those with AIHA and Evans syndrome often look like completely round spheres.

Many blood tests can look for signs of hemolysis (destruction of red blood cells). If your immune system is attacking these cells due to AIHA or Evans syndrome, you may have:

• High levels of bilirubin
• High levels of lactate dehydrogenase
• Low levels of haptoglobin

Coombs Test

If your doctor confirms you have hemolysis, they may recommend a Coombs test, also called a direct antiglobulin test. This test can identify antibodies that are attacking your red blood cells. It helps your doctor understand whether your low red blood cell levels are caused by AIHA or another condition.

This test can also help determine the cause of low red blood cell levels for people with Evans syndrome.

Other Tests

Your doctor may perform other tests to diagnose or rule out other health conditions that may be causing your blood cells to be destroyed. For example, lupus, liver disease, kidney disease, infections, and cancer can cause hemolysis. If you have low red blood cell levels but tests don’t indicate any of these other conditions, your doctor may diagnose you with AIHA or Evans syndrome.

If you have low levels of platelets or white blood cells, you may need additional testing. Low platelet levels may result from certain medications or problems with your liver, spleen, or bone marrow. A drop in white blood cell levels may occur with viral infections or leukemia. A doctor may diagnose you with Evans syndrome if they rule out other conditions.

AIHA and Evans Syndrome Treatment Options

AIHA can be treated with a variety of medications and procedures. However, Evans syndrome is usually more difficult to treat. In many cases, AIHA treatments don’t work well to control Evans syndrome.

For those with AIHA, treated symptoms usually improve quickly. People with mild disease may not require any therapy. On the other hand, most people with Evans syndrome need treatment. Effectiveness varies greatly from person to person — some people get better quickly, with symptoms staying away for a long time, while other people continue to experience health problems.

Doctors usually first recommend corticosteroids for AIHA and Evans syndrome. If these treatments don’t work, the following options may be helpful:

• Intravenous immunoglobulin (IVIG) — An infusion of antibodies from a donor
• Immunosuppressant drugs — Medications that help calm the immune system
• Splenectomy — Surgery to remove the spleen
• Blood transfusion — A procedure in which blood from a donor is infused

People with AIHA often receive immunosuppressant drugs like azathioprine (Imuran, Azasan), rituximab (Rituxan), and cyclophosphamide (Cytoxan, Neosar). The most common immunosuppressant medications used for Evans syndrome include cyclosporine (Gengraf, Neoral, Sandimmune) and mycophenolate mofetil (CellCept).

If your AIHA or Evans syndrome is caused by underlying health problems, your doctor will also treat the first condition. This strategy may help improve symptoms of AIHA or Evans syndrome.

Talk With Others Who Understand

On myAIHAteam, members with AIHA and their loved ones come together to ask questions, give advice, and share their stories with others who understand life with this rare disease.

Are you living with AIHA and Evans syndrome? What type of treatment have you received? Share your experience in the comments below, or start a conversation by posting on your Activities page.