Haemolytic disease of the newborn Flashcards
Define haemolytic disease of the newborn.
A condition with immune haemolysis of RBC in the newborn caused by transplacental passage of maternal antibodies against blood antigens.
What is the pathophysiology of haemolytic disease of the newborn?
Immune haemolytic anaemia of the newborn caused by antibodies to blood group antigens
Most important: anti-D (a ‘rhesus’ antigen), anti-A, anti-B (ABO antigens) and anti-Kell
Mother is always negative for these antigens and the baby is positive; the mother then makes antibodies against the baby’s blood group antigen and these antibodies cross the placenta into the baby’s circulation causing fetal or neonatal haemolytic anaemia.
Why has incidence of rhesus D haemolytic disease been reduced significantly? What is the biggest cause of HDN now?
Females who are rhesus D negative now receive Rh immunoglobulin/anti-D prophylaxis during pregnancy and shortly after birth to a rhesus-positive baby.
So ABO incompatibility is now the biggest cause of HDN.
What sensitising events can occur in the mother to cause HDN?
- Pregnancy alone* - fetal-maternal haemorrhage of only 0.1ml can cause this and often goes unrecognised
- Amniocentesis, chorionic villus sampling and cordocentesis can also cause this
- Transfusion
NB: there are rarely any problems during primary exposure but subsequent pregnancies result in large amounts of maternal anti-D antibodies being produced and risk increases with each gestation.
How is HDN diagnosed antenatally and postnatally?
Antenatally
- Indirect Coomb’s test - first antenatal visit, if positive then monitor. Alternatively, non-invasive rhesus genotyping of the fetus using free cell fetal DNA
- Antenatal US - detect signs of hydrops fetalis and Doppler or middle cerebral aretery for detection of anaemia
- Fetal blood sampling - FBC, biochemistry
Postnatally
- Neonatal or umbilical cord blood sampling - check for ABO and Rh group, direct Coombs test, Hb and baseline bilirubin. Positive DAT and ABO/Rh incompatibility supports diagnosis.
What test can differentate HDN from non-antibody mediated anaemias? Name 2 common causes of nonimmune haemolytic anaemias in neonates.
Direct anti-globulin test +ve (Coombs test) - this is negative in non-antibody mediated anaemias. Antenatally, presence of anti-D antibodies in the mother - detected by indirect Coombs test (all Rh-ve women get this test).
Non-immune haemolytic anaemias in newborns:
- G6PD deficiency
- Hereditary spherocytosis
How does HDN present?
- Normal in mild cases
- Jaundice (yellow amniotic fluid, yellow vermix, yellow skin)
- Kernicterus (bilirubin encephalopathy)
- Pallor
- Hepatosplenomegaly
- Hypoglycaemia
- Hydrops fetalis or polyhydramnios on US
- Subcutaneous oedema, pericardial effusion , pleural effusion, ascites
- Petechiae
What is the management of HDN in utero? What is the management postnatally?
Antenatally
- Transfusion - if blood samples confirm anaemia; best done at 18 weeks; IV transfusion of O negative blood cross-matched with maternal blood, given under US guidance into the umbilical vein.
- Monitor using Doppler to assess need for further transfusion
Postnatally
- Transfusion - required in 25% as hyperbilirubinaemia may develop in the first 24 hours, but 50% may have normal Hb initially then develop anaemia at 6-8 weeks so monitor
- Phototherapy - to prevent kernicterus
- IVIg - early administration in HDN has been shown to reduce haemolysis
What are the complications of HDN?
If rate of red cell destrucion exceeds rate of production then fetal/neonatal anaemia results which in severe cases can lead to:
- fetal heart failure
- fetal fluid retention
- fetal swelling (hydrops)
- neonatal jaundice with risk of kernicterus (not a problem during pregnancy as the placenta clears the bilirubin but immature liver alone cannot)
Recall 4 causes of jaundice in the first 24 hours of life.
Rhesus haemolytic disease
ABO haemolytic disease
Hereditary spherocytosis
Glucose-6-phosphodehydrogenase
Recall 3 causes of jaundice from days 2-14.
Common and usually physiological and seen in breastfed babies
Recall 5 causes of prolonged jaundice.
- Biliary atresia
- Hypothyroidism
- Galactosaemia
- UTI
- Breast milk jaundice - high conc of beta-glucuronidase –> increased unconjugated bilirubin absorption
- Prematurity - immature liver
- Congenital infection - CMV, toxoplasmosis
What is the prognosis of HDN?
Survival is good >90%
Neurodevelopment normal in >90%
Describe the anti-D prophylaxis administration.
RAADP = routine antenatal anti-D prophylaxis
15% of mothers are Rh -ve and so can be sensitised which can have complications for future pregnancies
Anti-D Ig given to all Rh-ve mothers who have not yet been sensitised
500U given at 28 and 34 weeks or 1500U single dose at 28 weeks (no difference in efficacy of regimens)
