Skip to main content

Saturn Medic

Clinical Subject Page

Autoimmune Hemolytic Anemia (AIHA)

Autoimmune Hemolytic Anemia (AIHA) is an acquired immune-mediated disorder in which autoantibodies target red blood cells, causing their premature destruction and resulting in hemolytic anemia. Hemolysis may occur within the spleen (extravascular) or the circulation (intravascular)

Also called

Immune Hemolytic Anemia

ICD-10

D59.1

Specialty

Hematology

Onset

Acute & Chronic

Reviewed

August 2026

On This Page

Overview

Autoimmune Hemolytic Anemia (AIHA) occurs when the immune system produces antibodies against red blood cells. Warm AIHA (IgG-mediated) is the most common type and usually causes extravascular hemolysis in the spleen, whereas Cold AIHA (IgM-mediated) activates complement and often causes hemolysis after cold exposure.

Patients typically present with anemia, jaundice, reticulocytosis, and laboratory evidence of hemolysis. The Direct Antiglobulin (Coombs) Test is the key diagnostic investigation.

Etiology & Risk Factors

-Primary (Idiopathic) cause of Autoimmune Hemolytic Anemia (AIHA)

  • No identifiable underlying cause

-Secondary Causes of Autoimmune Hemolytic Anemia (AIHA)

Autoimmune Diseases

  • Systemic lupus erythematosus

  • Rheumatoid arthritis

  • Autoimmune thyroid disease

Lymphoproliferative Disorders

  • Chronic lymphocytic leukemia (CLL)

  • Non-Hodgkin lymphoma

  • Hodgkin lymphoma

Infections

  • Mycoplasma pneumoniae

  • Epstein-Barr virus (EBV)

  • Cytomegalovirus (CMV)

  • HIV

Drugs

  • Penicillin

  • Cephalosporins

  • Methyldopa

  • Fludarabine

-Risk Factors

  • Autoimmune disease

  • Lymphoid malignancy

  • Recent infection

  • Certain medications

  • Older age (especially Warm AIHA)

Pathophysiology

Autoantibody formation against red blood cell surface antigens → antibody-coated red blood cells are recognized by macrophages or activate complement → premature red blood cell destruction → hemolytic anemia.

-Warm AIHA

IgG antibodies bind red blood cells at body temperature → splenic macrophages remove antibody-coated RBCs → extravascular hemolysis.

-Cold AIHA

IgM antibodies bind RBCs at low temperatures → complement activation → intravascular and extravascular hemolysis, primarily in the liver.

Clinical Presentation

-Symptoms

  • Fatigue

  • Weakness

  • Pallor

  • Jaundice

  • Dark urine

  • Shortness of breath

  • Dizziness

  • Palpitations

-Signs

  • Pallor

  • Jaundice

  • Splenomegaly (especially Warm AIHA)

  • Mild hepatomegaly

  • Tachycardia

-Cold Autoimmune Hemolytic Anemia (AIHA) Features

  • Acrocyanosis

  • Raynaud-like symptoms

  • Hemolysis after cold exposure

History Taking

-Ask about:

  • Fatigue
  • Jaundice
  • Dark urine
  • Previous hemolytic episodes
  • Cold sensitivity
  • Recent infections
  • Autoimmune disease
  • Malignancy
  • Medication history
  • Blood transfusions
  • Family history
  •  

Physical Examination

-General Examination

Look for:

  • Pallor

  • Jaundice

  • Fever

  • Tachycardia

-Abdominal Examination

Assess for:

  • Splenomegaly

  • Hepatomegaly

-Peripheral Examination

Look for:

    • Acrocyanosis

    • Peripheral cyanosis

    • Signs of underlying autoimmune disease

Investigations

-Complete Blood Count (CBC)

Typical findings:

  • Low hemoglobin

  • Increased reticulocyte count

  • Variable MCV (may be increased due to reticulocytosis)

-Peripheral Blood Film

May show:

  • Spherocytes (Warm AIHA)

  • Polychromasia

  • RBC agglutination (Cold AIHA)

-Hemolysis Screen

  • Increased indirect bilirubin

  • Increased LDH

  • Low haptoglobin

  • Increased reticulocyte count

-Direct Antiglobulin (Coombs) Test (Gold Standard)

  • Positive in most cases

  • Detects IgG and/or complement bound to red blood cells

Indirect Antiglobulin Test

  • May identify circulating antibodies

Additional Investigations

To identify underlying causes:

    • ANA

    • Serum protein electrophoresis

    • Immunoglobulin levels

    • Viral serology (HIV, EBV, CMV, Mycoplasma)

    • CT imaging if lymphoma is suspected

    • Bone marrow examination when indicated

Diagnosis

Diagnosis is based on:

  • Clinical features of hemolysis
  • Positive Direct Antiglobulin (Coombs) Test
  • Laboratory evidence of hemolysis
  • Identification of any underlying disease
Home / Home / Clinical Cases / Hematology System Clinical Cases / Autoimmune Hemolytic Anemia (AIHA)
Related Topics

Management

-Initial Management

  • Treat the underlying cause

  • Supportive care

  • Folic acid supplementation

  • Blood transfusion if severe symptomatic anemia (when necessary)

-Warm AIHA

First-line:

  • Corticosteroids (Prednisolone)

Second-line:

  • Rituximab

  • Splenectomy (selected patients)

  • Immunosuppressive agents (e.g., azathioprine, mycophenolate mofetil, cyclophosphamide)

-Cold AIHA

  • Avoid cold exposure

  • Rituximab is first-line therapy for symptomatic disease

  • Complement inhibitors (selected patients)

  • Corticosteroids are generally less effective than in Warm AIHA

Complications

  • Severe anemia
  • Heart failure
  • Thromboembolism
  • Hemolytic crisis
  • Gallstones
  • Splenomegaly
  • Treatment-related immunosuppression
  • Relapse

Prognosis

The prognosis depends on the underlying cause and the response to treatment. Many patients with Warm AIHA respond well to corticosteroids, although relapses are common. Cold AIHA tends to follow a chronic course but can often be controlled with avoidance of cold exposure and targeted therapy. Early diagnosis and treatment improve outcomes.

Key Points / Clinical Pearls

  • Autoimmune Hemolytic Anemia (AIHA) is an acquired immune-mediated hemolytic anemia.
  • The two major types are Warm AIHA (IgG) and Cold AIHA (IgM).
  • Warm AIHA is the most common form.
  • Patients present with anemia, jaundice, and laboratory evidence of hemolysis.
  • The Direct Antiglobulin (Coombs) Test is the key diagnostic test.
  • Warm AIHA commonly shows spherocytes on the peripheral blood film.
  • Corticosteroids are the first-line treatment for Warm AIHA.
  • Rituximab is an important therapy for refractory Warm AIHA and symptomatic Cold AIHA.
  • Always investigate for underlying autoimmune disease, infection, or lymphoproliferative malignancy.
  • Prognosis is generally good with timely diagnosis and appropriate treatment.
  • Tripathi AK, Chuda R. National Center for Biotechnology Information (NIH). Laboratory Evaluation of Immune Hemolytic Anemias, StatPearls.
  • Jager U, Barcellini W, Broome CM, et al. Diagnosis and Treatment of Autoimmune Hemolytic Anemia in Adults: Recommendations From the First International Consensus Meeting. Blood Rev. 2020;41:100648.
  • Autoimmune Hemolytic Anemia in the Pediatric Setting. J Clin Med. 2021;10:216. PMC7828053.
  • Barcellini W, Fattizzo B. Autoimmune Hemolytic Anemia: Current Understanding of Pathogenesis and Treatment. Front Immunol. EHA Library.
  • MedlinePlus, National Library of Medicine (NIH). Autoimmune Hemolytic Anemia: Medical Encyclopedia.