Autoimmune Hemolytic Anemia (AIHA)

How autoimmune hemolytic anemia happens

Red blood cells normally live about 120 days. In AIHA, antibodies stick to the red cell surface. Cells coated with antibodies are either removed by the spleen and liver, or destroyed directly in the bloodstream when proteins called complement are activated. The bone marrow speeds up production, but if destruction outpaces production, anemia develops.

When red cells break down, they release hemoglobin, which is converted to bilirubin. Excess bilirubin causes jaundice. Hemoglobin released directly into the blood can pass into the urine and make it dark.

Types of AIHA

Causes

• Primary (idiopathic): no underlying cause is found in about half of cases.
• Secondary: - Autoimmune diseases: lupus and others - Blood cancers: chronic lymphocytic leukemia and lymphoma - Infections: Mycoplasma pneumonia and Epstein-Barr virus (cold types), viral infections in children - Medicines: including some antibiotics and checkpoint inhibitor cancer drugs - Immune deficiency and after stem cell transplant

Symptoms

• Tiredness and weakness
• Shortness of breath, especially on exertion
• Pale skin
• Fast heartbeat or palpitations
• Jaundice: yellow skin or eyes
• Dark urine
• Enlarged spleen, causing fullness under the left ribs
• Dizziness and headaches
• In cold agglutinin disease: blue or white fingers, toes, ears and nose in the cold (acrocyanosis), and symptoms worse in winter

Onset can be gradual over weeks or sudden over days.

Diagnosis

• Complete blood count: low hemoglobin. Platelets may also be low in Evans syndrome (AIHA plus low platelets).
• Reticulocyte count: usually raised, showing the marrow is responding.
• Markers of hemolysis: high LDH and unconjugated bilirubin, low haptoglobin.
• Blood smear: spherocytes in warm AIHA, clumped red cells in cold agglutinin disease.
• Direct antiglobulin test (DAT, Coombs test): the key test. It detects antibodies or complement on red cells, and shows whether IgG, complement or both are present, which helps classify the type.
• Cold agglutinin titer for suspected cold disease.
• Tests for underlying causes: autoimmune antibodies, CT scans for lymph node enlargement, bone marrow examination, infection tests and a medication review.

Other causes of hemolysis, such as G6PD deficiency, hereditary spherocytosis and microangiopathic hemolytic anemia, are DAT-negative and need different treatment.

Treatment

Warm AIHA

• Corticosteroids (such as prednisone) are first-line and work in most people within 1 to 3 weeks, then are tapered slowly over months.
• Rituximab, an antibody that removes B cells, is increasingly used early or for relapse.
• Other options for resistant cases include other immunosuppressants, newer targeted drugs, and splenectomy.
• Folic acid supports increased red cell production.

Cold agglutinin disease

• Avoid cold: dress warmly, cover hands, feet and ears, warm IV fluids and blood if transfused.
• Rituximab, alone or with other drugs, for symptomatic disease.
• Sutimlimab, a complement inhibitor, is approved in the US for cold agglutinin disease.
• Steroids are generally not effective for cold types.

General measures

• Blood transfusion for severe or life-threatening anemia, with careful matching.
• Treat the underlying cause: for example, treating lymphoma or stopping a causative drug.
• Blood clot prevention: AIHA increases the risk of blood clots, especially during active hemolysis.
• Vaccinations before rituximab or splenectomy.

Outlook

Most people with warm AIHA respond to initial treatment, but relapses are common, and some need long-term therapy. Cold agglutinin disease is usually chronic but manageable. Infection-related cold AIHA in children often resolves within weeks. Outcomes in secondary AIHA depend largely on the underlying condition. Regular blood tests help catch relapses early.

Frequently asked questions

What is autoimmune hemolytic anemia?

Autoimmune hemolytic anemia is a condition in which the immune system makes antibodies against your own red blood cells and destroys them. This causes anemia, with tiredness, breathlessness, pale skin, and often jaundice and dark urine. It can be warm or cold type depending on the antibodies involved.

What is the difference between warm and cold AIHA?

In warm AIHA, antibodies (usually IgG) attack red cells at body temperature, and the spleen removes them. It is the most common type and responds to steroids. In cold agglutinin disease, IgM antibodies act in cooler parts of the body, so symptoms worsen in the cold. Steroids work poorly for cold types.

What causes autoimmune hemolytic anemia?

About half of cases have no identifiable cause. The rest are linked to autoimmune diseases such as lupus, blood cancers such as chronic lymphocytic leukemia and lymphoma, infections such as Mycoplasma pneumonia and mononucleosis, and some medicines.

Is autoimmune hemolytic anemia curable?

Many people achieve remission with treatment, particularly with steroids and rituximab, and some stay in remission for years. Relapses are common, so long-term monitoring is needed. When AIHA is caused by an infection or a medicine, it often resolves once the trigger is gone.

What is a Coombs test?

The direct Coombs test, or direct antiglobulin test, checks whether antibodies or complement proteins are attached to your red blood cells. A positive result supports a diagnosis of autoimmune hemolytic anemia and helps doctors determine whether it is the warm or cold type.