Makindo Medical Notes

Related Subjects: | Alpha Thalassaemia | Anaemia of Chronic Disease | Aplastic Anaemia | Autoimmune Haemolytic Anaemia (AIHA)

Autoimmune Haemolytic Anaemia (AIHA) is a group of anaemias in which increased haemolysis is caused by antibodies directed against the patient's own red blood cells (RBCs). These autoantibodies are usually of the IgG or IgM type.

About

• Antibodies to red blood cells shorten red cell survival.
• May involve IgG or IgM antibodies (rarely IgA or IgE).
• Complement fixation can lead to intravascular haemolysis.
• Antibodies can be more active at different temperatures.
• Those active at 37°C are termed "warm antibodies," while those active below 37°C are "cold antibodies."

Aetiology

• Autoantibodies are directed against RBC surface antigens.
• These antibodies can cause agglutination when antihuman globulin is added.
• In warm AIHA, the most common targets are Rhesus (Rh) polypeptides.
• Interaction with splenic macrophages may result in phagocytosis of the entire cell or partial phagocytosis leading to spherocyte formation.

Causes

• Idiopathic (50%): No identifiable underlying cause.
• Secondary (50%):
  • Medications: Methyldopa, mefenamic acid, L-dopa, penicillin, cephalosporins.
  • Malignancies: Lymphomas, chronic lymphocytic leukaemia (CLL).
  • Autoimmune Diseases: Systemic lupus erythematosus (SLE), rheumatoid arthritis.
  • Infections:
    • Mycoplasma pneumoniae.
    • Epstein-Barr virus (infectious mononucleosis).
    • Cytomegalovirus (CMV).
  • Other Conditions: Ulcerative colitis, paroxysmal cold haemoglobinuria (PCH).

Classification by Temperature

• Warm Autoimmune Haemolytic Anaemia: Antibodies react best at 37°C.
  • Usually involves IgG antibodies.
  • More common type of AIHA.
  • Associated with autoimmune diseases (e.g., SLE), certain drugs, and lymphomas.
  • Treatment may include corticosteroids and immunosuppressive agents; splenectomy may be considered.
• Cold Autoimmune Haemolytic Anaemia (Cold Agglutinin Disease): Antibodies react best below 37°C.
  • Usually involves IgM antibodies, with maximum activity at 4°C.
  • Complement-mediated intravascular haemolysis occurs.
  • Haemolysis occurs in cooler parts of the body (e.g., fingers, toes, ears).
  • Associated with infections (e.g., Mycoplasma pneumoniae, Epstein-Barr virus) and lymphomas.
  • Patients may experience acrocyanosis (bluish discoloration of extremities) and Raynaud's phenomenon.

Clinical Features

• Symptoms of anaemia: Weakness, pallor, fatigue.
• Jaundice due to increased bilirubin from haemolysis.
• Dark urine (haemoglobinuria), especially in cold agglutinin disease during cold exposure.
• Splenomegaly may be present due to increased destruction of RBCs.

Investigations

• Full Blood Count (FBC): Anaemia, often macrocytic due to reticulocytosis.
• Peripheral Blood Smear: Shows polychromasia, spherocytes (in warm AIHA), and nucleated RBCs.
• Haemolysis Markers: Elevated lactate dehydrogenase (LDH), indirect hyperbilirubinemia, low haptoglobin levels.
• Direct Antiglobulin Test (DAT/Coombs Test):
  • Positive in AIHA.
  • Warm AIHA: DAT positive for IgG (± complement).
  • Cold AIHA: DAT positive for complement (C3) only.
• Cold Agglutinin Titre: May be elevated in cold AIHA.

Management

• General Supportive Care:
  • Transfusions if necessary; cross-matching may be challenging.
  • Treat any underlying cause or precipitating factors.
• Warm AIHA:
  • First-line treatment is corticosteroids (e.g., prednisolone).
  • If refractory, consider immunosuppressive agents (e.g., azathioprine, cyclophosphamide) or rituximab.
  • Splenectomy may be considered in severe or unresponsive cases.
• Cold AIHA:
  • Avoid cold exposure; keep warm.
  • Treat underlying infections or conditions.
  • Rituximab may be effective.
  • Plasma exchange in severe cases.

References

• Autoimmune Haemolytic Anemia: A Practical Review
• American Society of Hematology: Immune Haemolytic Anemia