Overview

Autoimmune haemolytic anaemia (AIHA) is an autoimmune condition in which red blood cells undergo haemolysis due to antibodies directed against red blood cells. It can be divided into:

  • Warm-type AIHA – (usually) IgG antibodies cause haemolysis at core body temperature (37°C)
  • Cold-type AIHA – IgM and sometimes IgG antibodies cause haemolysis at lower temperatures (usually <30°C)

The causes of AIHA are not fully understood.

It may be helpful to look at the chapter on Anaemia: Data Interpretation alongside reading this section to help wrap your head around when to suspect what type of anaemia.

Warm AIHA: pathogenesis

In warm AIHA, at core body temperature, IgG antibodies bind to red blood cells. The Fc receptors of these antibodies are recognised by macrophages resulting in red blood cell membrane destruction.

As they destroy the red blood cell membrane, the red blood cells become more spherical, resulting in spherocytes. Spherocytes are more fragile than standard red blood cells and are therefore destroyed more easily, resulting in excess splenic red blood cell destruction and splenomegaly.

Therefore, warm AIHA tends to cause extravascular haemolysis.

Cold AIHA: pathogenesis

In cold AIHA, at colder temperatures (<30°C), IgM antibodies bind to red blood cells. Instead of stimulating macrophages as seen in warm AIHA, these antibodies activate the complement system, resulting in the formation of the membrane attack complex, leading to the red cell bursting and releasing its contents.

Therefore, cold AIHA tends to cause intravascular haemolysis (increased bilirubin, increased lactate dehydrogenase, decreased haptoglobins). 

Associations

Example History

A 35-year-old man has painful hands that change colour from red to blue when he goes out in cold weather.

Investigations:

Haemoglobin:70 g/L(115 – 180 g/L)
Platelets:200 x 109/L(150 – 450 x 109/L)
Mean cell volume (MCV):81.0 fL(77.0 – 91.0 fL)
White blood cells (WBC):6.0 x 109/L(5.0 – 12.0 x 109/L)
Reticulocyte count:2.3 %(0.2 – 2.0 %)
Peripheral smear:Spherocytes seen
Direct antiglobulin test:Positive

Presentation

The following features may be present:

  • Pallor
  • Fatigue
  • Dyspnoea
  • Splenomegaly – seen in warm AIHA due to extravascular haemolysis
  • Jaundice – if bilirubinaemia is high enough in cold AIHA due to intravascular haemolysis
  • Raynaud’s phenomenon in cold-type AIHA
    • Due to the agglutination of blood cells in the capillaries of the extremities

Investigations

Overview

  • Full blood count (FBC):
    • Shows normocytic, normochromic anaemia
  • Reticulocyte count:
    • Increased – the bone marrow responds by trying to create new, immature red cells 
  • Blood film:
    • Spherocytes may be seen in both warm and cold AIHA
    • Reticulocytes are seen
  • Urinalysis:
    • May show haemoglobinuria – if intravascular haemolysis is occurring
    • Urine dipstick shows urobilinogen – if intravascular haemolysis is occurring
  • Markers of intravascular haemolysis:
    • Bilirubin:
      • Raised – due to haemolysis and haemoglobin breakdown
    • Lactate dehydrogenase (LDH):
      • Elevated, but not specific
    • Haptoglobins:
      • Low – haptoglobins bind to free haemoglobin
  • Direct antiglobulin test (Coomb’s test) – a key test:
    • Positive – if this is positive, this suggests there is an immune component to haemolysis

Management

Warm-type AIHA

  • 1st-line: corticosteroids + consider immunosuppressants e.g. azathioprine/cyclophosphamide

Cold-type AIHA

  • 1st-line: supportive measures + stay warm e.g. wear clothing and take cold-weather precautions

Complications

  • Cold-type AIHA:
    • Necrosis of extremities in cold exposure
    • Severe anaemia
    • Emergence of underlying malignancy in patients initially thought to have idiopathic cold-type AIHA
    • High-output cardiac failure
  • Warm-type AIHA:
    • Severe anaemia
    • High-output cardiac failure

Prognosis

  • In idiopathic cases, the prognosis is generally good
  • Those with underlying causes have a worse prognosis

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