FRCPath Haematology Part 2: Morphology Acquired Haemolytic Anaemias Haemolytic Disease of the Newborn
  • Haemolytic disease of the fetus / newborn (HDFN) is caused by maternal antibodies against fetal red cell antigens.
  • IgG antibodies can cross the placenta and cause haemolysis.
  • Incidence of clinically-significant antibodies in pregnancy: 0.3-1%.
  • Greatest risk with anti-D, anti-c and anti-K (and all other Kell system antigens, e.g. anti-k, -Kpa, -Kpb, -Jsa, -Jsb) .
  • ABO incompatibility may also cause haemolysis.
  • Maternal blood group should be checked at booking and 28 weeks to determine ABO/Rh status and screen for clinically significant red cell antibodies (e.g. anti-D, -c, -K)
    • If detected, further testing should be done to assess the likelihood of these causing HDFN
    • Antibody titres should also be measured once every four weeks until 28 weeks, then once every 2 weeks till delivery
      • Moderate risk of HDFN: anti-D levels 4-15 IU/ml, anti-c 7.5-20 IU/ml
      • Severe risk of HDFN: anti-D levels of >15 IU/ml, anti-c >20 IU/ml
    • If the mother has clinically-significant antibodies, then the father and fetus should be tested to ascertain the risk of the fetus carrying the relevant antigen
      • Free fetal DNA can be extracted from the maternal circulation from 16 weeks
  • If the fetus is antigen positive and the mother has clinically-significant antibodies, then the pregnancy must be monitored closely. Middle cerebral artery peak systolic velocity is a non-invasive and sensitive way of detecting fetal anaemia.
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Blood film features:

  • Spherocytes
  • Polychromasia
  • Circulating nucleated red blood cells
  • Polychromasia and circulating nRBCs may be absent in Kell haemolytic disease of the newborn because of associated marrow suppression.

Differential diagnosis:

  • Hereditary spherocytosis

Other resources:

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