Anti-D – Rh(D) Negative Women
https://ranzcog.edu.au/wp-content/uploads/Anti-D-Guidelines.pdf
🔴 Background & Rationale
- ~1 in 7 women are Rh(D) negative.
- Risk of sensitisation if fetal blood (Rh[D] positive) enters maternal circulation.
- Sensitisation can lead to haemolytic disease of the fetus/newborn in current or future pregnancies.
- Anti-D prevents maternal immune response by neutralising fetal D+ red cells.
📌 When to Offer Anti-D (Key Indications)
First Trimester (250 IU)
- Indicated for:
- Abortion (≥10 weeks; medical/surgical)
- Miscarriage
- Ectopic pregnancy
- Molar pregnancy
- Chorionic villus sampling (CVS)
- Threatened miscarriage:
- Routine use not supported <12 weeks.
- May be considered if heavy/repeated bleeding, abdominal pain, pelvic trauma.
Second & Third Trimester (625 IU)
- Sensitising events requiring Anti-D:
- Obstetric haemorrhage
- Amniocentesis or invasive fetal procedures
- External cephalic version (successful or not)
- Abdominal trauma / suspected feto-maternal bleeding
- Abortion
Routine Antenatal Prophylaxis (625 IU)
- All Rh(D)-negative women (without preformed antibodies):
- 28 weeks
- 34 weeks
- Exception: Not required if fetal RHD genotyping confirms Rh(D)-negative fetus.
Postpartum
- If infant is Rh(D) positive:
- Quantify feto-maternal haemorrhage
- Administer appropriate Anti-D dose within 72 hours.
- Follow Kleihauer test result to determine dose.
Testing Before Anti-D Administration
- Before any Anti-D: Check maternal Rh antibody titre to detect existing sensitisation.
- At 34 weeks: Can omit titre if Anti-D was given at 28 weeks.
When NOT to Give Anti-D
- If woman has preformed Anti-D antibodies, except if due to previous Anti-D administration (passive immunity).
If Rh(D) Antibody Status Unclear
- Check patient record or consult treating clinician.
- If doubt persists → Administer Anti-D as precaution.
Administration Details
- IM injection recommended.
- In high BMI → deltoid may be preferred over gluteal site.
- If >4 doses required → consider IV Anti-D (e.g., Rhophylac®).
Cell-Free DNA Testing
- Non-invasive prenatal testing (NIPT) for fetal Rh(D) genotype is feasible from 11+0 weeks.
- Women carrying Rh(D)-negative fetuses do not require Anti-D.
Available Anti-D Products in Australia
| Product | Dose | Manufacturer | Route |
|---|---|---|---|
| CSL 250 IU | 50 mcg | CSL Behring | IM |
| CSL 625 IU | 125 mcg | CSL Behring | IM |
| Rhophylac® 1500 IU | 300 mcg | CSL Behring | IM or IV (not available in NZ) |
🔍 Evidence Summary
- Cochrane Review (Level I): Antenatal Anti-D reduces alloimmunisation by ~78%.
- NICE Review (Level II/III): Reduction by ~70%.
- Anti-D at 28 & 34 weeks reduces sensitisation from 1% → 0.35%.
Rh isoimmunisation
is an immune response that occurs when an Rh(D)-negative individual (usually the mother) is exposed to Rh(D)-positive red blood cells (usually from the fetus), leading to the production of anti-D antibodies.
🧪 Mechanism of Isoimmunisation
- Fetal-maternal haemorrhage (FMH) occurs → fetal Rh(D)+ red blood cells enter maternal circulation.
- The Rh(D)-negative mother’s immune system recognises Rh(D) as foreign.
- Mother produces IgG anti-D antibodies.
- In future pregnancies, if the fetus is Rh(D)+ again, these maternal antibodies cross the placenta, leading to:
- Haemolysis of fetal red cells
- Anaemia, jaundice, hydrops fetalis, or stillbirth
📉 Clinical Consequences
- First exposure: usually sensitises mother, fetus often unaffected.
- Subsequent pregnancies: high risk of haemolytic disease of the fetus and newborn (HDFN).
🚨 Haemolytic Disease of the Fetus/Newborn (HDFN)
- Ranges from mild jaundice → severe anaemia → hydrops fetalis → intrauterine death.
- Caused by maternal anti-D IgG antibodies destroying fetal Rh(D)+ RBCs.
📌 Risk Factors for Isoimmunisation
- Delivery of Rh(D)+ infant
- Miscarriage, abortion, ectopic pregnancy
- Invasive procedures (e.g. amniocentesis, CVS)
- Trauma, placental abruption
- External cephalic version
- Unrecognised fetomaternal bleeding