Antibodies (including use of Anti-D) in pregnancy Flashcards
Incidence of women with Rh negative blood group
1:7
When should women be offered Anti-d? (RANZCOG)
≤12 weeks (250IU):
- CVS
- Miscarriage (but insufficient evidence that THREATENED miscarriage before 12/40 needs Anti-D)
- Abortion (MTOP/STOP)
- Ectopic
- (NB twins = 625IU)
≥ 12 weeks - 2nd and 3rd trimester (starting dose 625IU):
- Obstetric haemorrhage
- Amniocentesis or other invasive procedure
- ECV (regardless of success)
- Abdominal trauma (or any other event that could cause bleeding)
- Abortion
- NHMRC recommends prophylactic dose 625IU at 28 and 34 wks
Postnatally:
- within 72 hours if baby Rh +ve on cord blood
Kleihauer should be taken to determine extent of fetomaternal haemorrhage and anti-D dose in 2nd/3rd trimesters and postnatally.
How to administer Anti-D?
- Deep IM injection (can use deltoid if obese)
- Take G+H first to ensure no antibodies present
- Do not give if mother already sensitised, though always check if this is passive acquisition after Anti-D administration (which does NOT preclude giving further anti-D doses)
When should women have their blood group and antibody status checked?
Blood group and antibody status determined at:
- booking
- 28/40
- prior to any Anti-D administration
- After potentially sensitising events
What are the implications for the fetus and neonate from red cell antibodies?
- Severe fetal anaemia / HDFN, leading to…
- Hydrops
- Invasive procedures
- Preterm birth
- Stillbirth
Increased risk for neonate:
- anaemia, jaundice, kernicterus and increased perinatal morbidity and mortality.
When and how should paternal and fetal genotyping be performed?
Where clinically significant maternal red cell antibodies are detected, the paternal phenotype can be ascertained by serology.
For rhesus D (RhD) antigen: in an antigen-positive father, genotyping is required to determine whether he is homozygous or heterozygous for the RHD gene.
Non-invasive fetal genotyping using maternal blood (NIPT) is now possible for D, C, c, E, e and K antigens.
For other antigens, invasive testing (chorionic villus sampling [CVS] or amniocentesis) may be considered if fetal anaemia is a concern or if invasive testing is performed for another reason (e.g. karyotyping).
Once antibodies identified, when should referral to a fetal medicine specialist take place?
- rising antibody levels/titres,
- a level/titre above a specific threshold
- anti-D >/= 4 IU/ml
- anti-c >/= 7.5 IU/ml
- Anti-K any titre
- All other low risk Abs >/= 32 IU/ml
- ultrasound features suggestive of fetal anaemia.
What thresholds should be used for the various antibodies that could cause fetal anaemia to trigger referral for further investigation or monitoring?
anti-D - >/= 4 IU/ml
anti-c - >/= 7.5 IU/ml
anti-E - potentiates effect of anti-c - so refer even at low levels if detected in presence of another antibody, particularly anti-c.
anti-K (kell) antibodies - once detected. As any level can be associated with severe haemolytic disease of the fetus/newborn.
All lower risk anti-bodies >/= 32 IU/ml.
Once detected how often should antibody levels be monitored during pregnancy?
For high risk antibodies (anti-c, anti-D, anti-K, anti-E) - measure every 4 weeks up to 28 weeks, then every 2 weeks until delivery.
For all other lower risk antibodies just recheck titres at 28 weeks.
How should pregnancies at risk of fetal anaemia be monitored?
The cause of the alloimmunisation, relevant past history and pregnancy outcomes should be
ascertained in order to generate an assessment of risk of HDFN.
Anti- D,c,K should be measured 4 weekly till 28 weeks, then 2 weekly till delivery.
All other lower risk Abs can be retested at 28 weeks.
All women at high risk of HDFN should be referred to MFM.
Criteria:
- anti-D >/= 4 iu/ml
- anti-c >/= 7.5 iu/ml
- anti-E - especially if also anti-c
- anti-K - any titre
- any other Abs with titre >/= 32 iu/ml
- US suggestive of fetal anaemia (raised MCA PSV, hydrops)
- Previous severe HDFN and/or previous fetal intrauterine infusion
If the antibody levels/titres rise to a level that increases risk of anaemia (as above) then weekly MCA-PSV needed
If MCA PSV >1.5MoM (multiples of the median) threshold or if there are other signs of fetal anaemia, consider invasive management (i.e. cord blood sampling and intrauterine transfusion).
(RCOG 2014)
What are the implications for the mother from red cell antibodies?
Delayed blood transfusion if needed
What cord blood investigations should be performed after delivery?
Cord samples should be taken for a direct antiglobulin test (DAT), haemoglobin and bilirubin levels.
How should the neonate be managed?
If High risk for fetal anaemia:
- Observe for development of jaundice/anaemia with bili and Hb levels
- assess neurobehavioural state
- Encourage regular feeding as dehydration can worsen jaundice
- Phototherapy or exchange transfusion may be required
Incidence of red cell antibodies
Antibodies in 1.2% pregnancies
Clinically significant- 0.4%
Why are red cell antibodies present?
The mother has mounted an immune response to previous exposure to red cell antigens that are not in her blood group, due to: previous pregnancy, transfusion or transplantation. As part of the adaptive immune response she will have long-term anti-bodies to this antigen, which will rise in response to future exposures/events whereby her blood comes into contact with the antigen again.
