Autoimmune Hemolytic Anemia: Causes, Symptoms, Diagnosis, and Treatment

Autoimmune Hemolytic Anemia (AIHA) is a complex blood disorder that occurs when the immune system produces antibodies that target and destroy red blood cells prematurely. This process, known as hemolysis, leads to a decrease in the number of red blood cells, causing anemia.

Causes of Autoimmune Hemolytic Anemia

The causes of AIHA are multifaceted and can be categorized into primary and secondary types.

Primary AIHA

In primary or idiopathic AIHA, the exact cause of the immune response against red blood cells remains unknown. This form of AIHA occurs in the absence of an identifiable underlying disease or external trigger. It is thought that certain genetic and environmental factors may predispose individuals to develop this condition, but the precise mechanisms are still under investigation.

Secondary AIHA

Secondary AIHA occurs as a consequence of other conditions or factors that trigger the autoimmune response. These include:

  • Autoimmune Disorders: Diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and ulcerative colitis can be associated with AIHA. In these disorders, the dysregulated immune system may extend its attack to include red blood cells.
  • Infections: Certain infections, particularly those caused by viruses such as Epstein-Barr virus, cytomegalovirus, and hepatitis, can lead to the transient development of AIHA. The immune response directed against the infectious agent may cross-react with red blood cells, causing their destruction.
  • Lymphoproliferative Disorders: Conditions like chronic lymphocytic leukemia and non-Hodgkin lymphoma can be linked to AIHA. The abnormal proliferation of lymphocytes can lead to the production of autoantibodies against red blood cells.
  • Medications: Some drugs, including certain antibiotics and anti-seizure medications, can induce AIHA. This reaction may occur due to the drug's interaction with the immune system or the red blood cell membrane, making the cells appear foreign to the body's defense system.
  • Neoplasms: Certain cancers, particularly those affecting the immune system, can be associated with AIHA. The malignant cells can produce substances that alter the immune response or directly produce autoantibodies against red blood cells.

Categorization by Antibody Binding Temperature

AIHA is categorized based on the temperature at which the antibodies bind to the red blood cells.

  1. Warm Autoantibody Anemia: This is the most common form of AIHA and occurs when the antibodies are active at a temperature equal to or higher than 37° C. It can occur spontaneously or in association with certain conditions including lymphoma, chronic lymphocytic leukemia, and other autoimmune diseases. Hemolysis primarily occurs in the spleen.
  2. Cold Autoantibody Anemia: This form of AIHA occurs when the reaction happens at lower temperatures. It can be idiopathic or secondary to lymphoproliferative syndromes and infections. Hemolysis mainly occurs in the liver's extravascular system.
  3. Mixed Forms: These are cases where characteristics of both warm and cold autoantibody anemia are present.

AIHA can also occur due to the intervention of alloantibodies in a hemolytic transfusion reaction or in hemolytic disease of the newborn. Additionally, certain medications can trigger AIHA by damaging the red blood cells and inducing hemolysis.

Symptoms of Autoimmune Hemolytic Anemia

The onset of AIHA can be sudden or gradual. The severity of symptoms can vary depending on the severity of hemolysis. Common symptoms include:

  • High fever
  • Severe weakness
  • Malaise
  • Headache
  • Severe pain in the lumbar region
  • Tachycardia and exertional dyspnea
  • Jaundice
  • Dark brown urine
  • Hemoglobinuria
  • Hepatosplenomegaly

In cold autoantibody disease, exposure to low temperatures can lead to additional signs such as acrocyanosis, Raynaud's syndrome, or ischemic incidents.

Diagnosis of Autoimmune Hemolytic Anemia

The diagnosis of AIHA involves a comprehensive approach that combines clinical evaluation with a series of laboratory tests. These steps are crucial for confirming the presence of hemolytic anemia, identifying its autoimmune nature, and distinguishing between warm and cold AIHA types.

Clinical Evaluation

The initial step in diagnosing AIHA involves a thorough clinical assessment, where the healthcare provider reviews the patient's medical history and symptoms. Common symptoms of AIHA include fatigue, pallor, jaundice, dark-colored urine, shortness of breath, and an enlarged spleen. The physician may also inquire about recent infections, medication use, and family history of autoimmune diseases.

Laboratory Tests

Scientist's hand holding a vial with blood samples arrayed on laboratory table

A series of laboratory tests are essential for diagnosing AIHA and include:

  • Complete Blood Count (CBC): This test measures levels of red blood cells, white blood cells, and platelets. In AIHA, it may show anemia with an increased number of reticulocytes (immature red blood cells) indicating the bone marrow's response to anemia.
  • Peripheral Blood Smear: A microscopic examination of the blood smear can reveal the presence of spherocytes (spherical red blood cells) in warm AIHA or agglutinated red blood cells in cold AIHA.
  • Direct Antiglobulin Test (DAT or Direct Coombs Test): This critical test detects antibodies or complement proteins attached to the surface of red blood cells. A positive DAT confirms the diagnosis of AIHA.
  • Indirect Antiglobulin Test (Indirect Coombs Test): This test detects antibodies in the patient's serum that can bind to red blood cells. It is used to identify the specific type of antibody causing AIHA.
  • Serum Bilirubin and Lactate Dehydrogenase (LDH): Elevated levels of these substances indicate increased red blood cell destruction.
  • Haptoglobin: This protein binds to free hemoglobin released from destroyed red blood cells. Low levels of haptoglobin are indicative of hemolysis.
  • Cold Agglutinin Titers: This test is specifically performed if cold AIHA is suspected, measuring the level and thermal range of cold agglutinins in the blood.

Further Testing

Depending on the initial findings, additional tests may be required to identify underlying conditions associated with AIHA, such as autoimmune diseases, lymphoproliferative disorders, or infections. These might include imaging studies, bone marrow biopsy, or specific serological tests.

The integration of clinical findings with laboratory results is essential for the accurate diagnosis of AIHA, guiding the appropriate treatment strategy and management plan.

Treatment of Autoimmune Hemolytic Anemia

The treatment approach is dependent on the specific cause of the condition. Common treatment options include:

  • Corticosteroids
  • Intravenous immunoglobulins
  • Immunosuppressants
  • Splenectomy

In cases where AIHA is drug-induced, discontinuing the administration of the causative agent can lead to remission of the disease.


Autoimmune Hemolytic Anemia is a complex condition that requires a comprehensive understanding for effective diagnosis and treatment. It is essential for individuals to seek medical attention if they experience symptoms associated with AIHA. Early detection and treatment can significantly improve the prognosis and quality of life for individuals with this condition. As always, this information is intended to supplement, not replace, the advice of healthcare professionals. Always consult with a healthcare provider for personalized medical advice.

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