Rh isoimmunisation and Anti-D

see also gynaecology

• Aust. Red Cross website with info. on blood products including Anti-D
• RANZCOG guidelines for use of Anti-D (pdf)
• Aust. Red Cross guidelines on use of Rh Anti-D (2024) (pdf)
• Western Health guideline (docx) - intranet only

• women who are Rh -ve and are pregnant are at risk of developing Rh iso-immunisation which is the development of permanent maternal antibodies against fetal Rh +ve red blood cell markers. Once this occurs and this fetus is Rh +ve, fetal haemolytic anaemia will result (hemolytic disease of the newborn or HDN) causing erythroblastosis fetalis which tends to be worse in magnitude with successive pregnancies and may cause fetal demise.
• although the rate of iso-immunisation developing in an otherwise uneventful pregnancy is approximately 1-2%, mismanagement of patients who present with increased risk may result in significant medicolegal issues.
• the minimum volume of RhD positive red cells that will immunise an RhD negative woman to make anti-D antibodies is of the order of 0.10-0.25 mL
  • iso-immunisation in the 1st trimester is very unlikely but Anti-D may still be advised in certain circumstances just to be sure

• risk factors for iso-immunisation sensitization and the potential indications for Anti-D are any circumstance that may allow fetal red blood cells into maternal circulation such as:
  • confirmed miscarriage
  • ectopic pregnancy
  • molar pregnancy
  • medical procedures such as amniocentesis, chorionic villous sampling, termination of pregnancy, fetal rotation
  • uterine bleeding in pregnancy after 12 weeks gestation - revealed or concealed
  • abruption
  • placenta praevia
  • stillbirth / FDIU
  • trauma to pregnant abdomen
  • Caesarian section or vaginal delivery (send cord blood as well)

• 17% of Caucasians (~15% of Australians) are Rh neg and 60% will carry a Rh positive baby
  • 5 in 6 Rh negative Caucasian women will have a Rh positive partner, 45% of which will be homozygous and 55% will be heterozygous
  • if the partner is homozygous for Rh +ve, the fetus will be Rh pos, if heterozygous, there is a 50% chance the fetus will be Rh pos.
• prior to Anti-D availability, an Rh neg women would have a 16% chance of becoming alloimmunized for Rh D antigen after the birth of 2 Rh pos infants (the use of routine post-partum Anti-D dropped this to 2% and the use of routine Anti-D in the 3rd TM further dropped this to 0.2%)
• prior to Anti-D availability, couples often had Rh testing before they were married to ensure compatibility
• the use of Anti-D has dropped HDN mortality due to Rh incompatibility from 46/100,000 births to 1.6/100,000 births
• Anti-D was then indicated for any potentially sensitizing event including any PV bleeding in pregnancy - the indications have recently been relaxed now to generally exclude threatened miscarriages in 1st TM and the dose has been reduced for the 1st TM events.

• routine 625IU Anti-D administration at:
  • 28wks
  • 34wks
  • post-partum
• sensitizing event administration of an appropriate dose of Anti-D within 72hrs of the risk event commencing (can be given up to 10 days but less effective)
• if intramuscular injection (IM) is contraindicated (severe thrombocytopenia, therapeutic anticoagulation, hereditary bleeding disorder), Rhophlyac 1500 IU should be administered intravenously.
• NB. mini-dose Anti-D of 250IU commenced in Australia in May 2001 due to shortages of Anti-D, this is sufficient to prevent immunisation by a fetomaternal haemorrhage of 2.5ml of RBC's (ie. 5ml of whole blood) and will cover any event in 1st trimester.

• in any Rh -ve patient who has the above risk factors, and are not known to be already iso-immunised (ie. do not already have Rh antibodies), she should be managed as follows:

• if no Rh Anti-D has been given within 1-2 weeks (the usual duration of action):
  • check Rh antibody levels:
    • if no antibodies give mini-dose Anti-D 250IU (625IU if multiple pregnancy)
    • if antibodies present:
      • confirm with laboratory that they were from recent Anti-D dose and whether sufficient amount:
        • if insufficient levels from recent Anti-D, consider repeat mini-dose AntiD
      • if maternal antibodies then refer to O&G for follow up and advice

• ideally, at 12-24wks gestation, all women who are Rh negative should have maternal blood test for fetal Rh group - Rhesus D non-invasive prenatal test (RHD NIPT)
  • this test has a sens 95% and spec 96% with PPV 97.6% and NPV 92.8% thus the risk of a false negative result is around 0.1-0.2% which would increase rates iso-immunization marginally but significantly reduce the need for Anti-D injections and avoids the requirement for an invasive amniocentesis to ascertain the fetal Rh status ¹⁾
  • the test may only be available at certain hospitals and can be done by Australian Red Cross LifeBlood but as of 2023, unfortunately, this test is only publicly funded for some women such as those already iso-immunized or those who cannot have Anti-D (including religious or cultural beliefs)
  • do not confuse this RHD NIPT with chromosome / genomic NIPT tests which look for chromosomal abnormalities in the fetus
• if fetus is Rh neg on NIPT no further Mx during pregnancy is required apart from confirmation testing on cord blood)
• if fetus is Rh +ve or no NIPT done:
  • check Rh antibody levels and if > 20wks gestation, request Kleihauer test (FBE tube, measures fetal RBC and assists with Anti-D dosing):
  • if no antibodies:
    • give Anti-D 625IU or more if indicated by Kleihauer test (this test is only needed if 20wks gestation or more)²⁾
      • a negative Kleihauer test does not remove the need for Anti-D
    • NB. patients with BMI > 30 and a feto-maternal haemorrhage > 6mL may require additional iv dose to increase bioavailability and facilitate more rapid clearance of fetal cells
    • Women with continued PV bleeding between 12 and 20 weeks gestation, should be offered Rh-D Ig at a minimum of 6-weekly intervals
  • if antibodies present:
    • confirm with laboratory that they were from recent Anti-D dose and whether sufficient amount:
      • if insufficient levels from recent Anti-D, consider repeat Anti-D 625IU
      • if maternal antibodies then refer to O&G and haematologist ASAP for follow up and advice