Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

unsensitised RhD-negative mother

1st line – anti-D immunoglobulin

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INITIAL
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unsensitised RhD-negative mother
1st line – 

anti-D immunoglobulin

Routine antenatal administration: anti-D immunoglobulin (also known as Rho(D) immune globulin in some countries) administered whether fetal blood type is unknown, or known to be RhD-positive. Single dose at 28 weeks’ gestation (either intravenously or intramuscularly).[23] Some guidelines recommend a single dose at around 28 weeks, or two doses at around 28 and 34 weeks of gestation.​[29][36][46]

Routine postnatal administration: anti-D immunoglobulin administered (either intravenously or intramuscularly) in women who have given birth to Rh-positive infants within 72 hours of delivery.[23]​​[29][46]​​​ The size of fetomaternal haemorrhage should be assessed, and further doses of anti-D immunoglobulin administered if required.[23][36]​​

The dose can vary depending on local guidelines, and factors such as brand of anti-D immunoglobulin.

Primary options

anti-D immunoglobulin: consult specialist for guidance on dose

Plus – additional anti-D immunoglobulin

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INITIAL
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unsensitised RhD-negative mother
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sensitising event: miscarriage/abortion and intrauterine fetal death
Plus – 

additional anti-D immunoglobulin

Treatment recommended for ALL patients in selected patient group

Additional anti-D immunoglobulin administration should not be given routinely following spontaneous miscarriage or abortion in the first trimester.[23]​ However, it may be considered on an individual basis, according to patient preferences.[23][27]​​

Anti-D immunoglobulin administration is recommended following pregnancy termination (either medical or surgical); or fetal death in the second or third trimester.[23][27]

Dose should be given within 72 hours of occurrence.[29][36] The dose can vary depending on local guidelines, and factors such as brand of anti-D immunoglobulin.

For sensitising events occurring after 20 weeks of pregnancy, size of fetomaternal haemorrhage should be assessed, and further doses of anti-D immunoglobulin administered if required.[36][50]​ 

Guidelines for anti-D immunoglobulin administration vary; follow local protocols.

Primary options

anti-D immunoglobulin: consult specialist for guidance on dose

Plus – additional anti-D immunoglobulin

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INITIAL
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unsensitised RhD-negative mother
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sensitising event: ectopic pregnancy
Plus – 

additional anti-D immunoglobulin

Treatment recommended for ALL patients in selected patient group

Additional anti-D immunoglobulin administration is recommended following all cases of ectopic pregnancy.[23]​ UK guidelines recommend that anti-D immunoglobulin should only be administered to Rh-negative women who have surgical management of an ectopic pregnancy (and not those who have solely medical management).[53]

Dose should be given within 72 hours of identification.[23][29][36] The dose can vary depending on local guidelines, and factors such as brand of anti-D immunoglobulin.

Guidelines for anti-D immunoglobulin administration vary; follow local protocols.

Primary options

anti-D immunoglobulin: consult specialist for guidance on dose

Plus – additional anti-D immunoglobulin

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INITIAL
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unsensitised RhD-negative mother
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sensitising event: molar pregnancy
Plus – 

additional anti-D immunoglobulin

Treatment recommended for ALL patients in selected patient group

Additional anti-D immunoglobulin is advised to be administered in all molar pregnancies (due to the difficulty in differentiating between complete and partial forms).[23][46] 

Dose should be given within 72 hours of identification.[29][36] The dose can vary depending on local guidelines, and factors such as brand of anti-D immunoglobulin.

Primary options

anti-D immunoglobulin: consult specialist for guidance on dose

Plus – additional anti-D immunoglobulin

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INITIAL
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unsensitised RhD-negative mother
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sensitising event: invasive procedures (e.g., chorionic villus sampling, amniocentesis)
Plus – 

additional anti-D immunoglobulin

Treatment recommended for ALL patients in selected patient group

Additional anti-D immunoglobulin administration is recommended following invasive diagnostic procedures such as chorionic villus sampling or amniocentesis.[23]

Dose should be given within 72 hours of occurrence.[29][36] The dose can vary depending on local guidelines, and factors such as brand of anti-D immunoglobulin.

If carried out after 20 weeks of pregnancy, size of fetomaternal haemorrhage should be assessed, and further doses of anti-D immunoglobulin administered if required.[36][50]​​

Primary options

anti-D immunoglobulin: consult specialist for guidance on dose

Plus – additional anti-D immunoglobulin

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INITIAL
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unsensitised RhD-negative mother
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sensitising event: bleeding/abdominal trauma in pregnancy
Plus – 

additional anti-D immunoglobulin

Treatment recommended for ALL patients in selected patient group

Additional anti-D immunoglobulin is recommended for antenatal haemorrhage after 20 weeks of gestation, and abdominal trauma.[23]​

Dose should be given within 72 hours of occurrence.[29][36] The dose can vary depending on local guidelines, and factors such as brand of anti-D immunoglobulin.

Consider quantitative testing for fetomaternal haemorrhage following events occurring after 20 weeks, or those potentially associated with placental trauma and disruption of the fetomaternal interface (e.g., placental abruption, blunt trauma to the abdomen, cordocentesis, placenta praevia with bleeding).[29]​ Administer further doses of anti-D immunoglobulin if required.[36]

Primary options

anti-D immunoglobulin: consult specialist for guidance on dose

Plus – additional anti-D immunoglobulin

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INITIAL
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unsensitised RhD-negative mother
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sensitising event: external cephalic version in breech presentation
Plus – 

additional anti-D immunoglobulin

Treatment recommended for ALL patients in selected patient group

Additional anti-D immunoglobulin administration is recommended following external cephalic version.[23]​ Quantitative testing for fetomaternal haemorrhage may also be considered.[29]​

Dose should be given within 72 hours of occurrence.[29][36] The dose can vary depending on local guidelines, and factors such as brand of anti-D immunoglobulin.

Primary options

anti-D immunoglobulin: consult specialist for guidance on dose

sensitised RhD-negative mother

1st line – seek specialist obstetric advice

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INITIAL
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sensitised RhD-negative mother
1st line – 

seek specialist obstetric advice

If antibody screening identifies anti-D antibodies in an RhD-negative pregnant woman, and assessments conclude that their presence is active, not passive, the patient should be considered sensitised, and specialist obstetric advice should be sought.[50]​ Rh immunoprophylaxis is no longer given.[34]

The initial management of an RhD-sensitised pregnancy involves the determination of the paternal rhesus status. If paternity is certain, and the father is RhD-negative, no further assessment/intervention is necessary. All children from a homozygous RhD-positive father will be RhD-positive, and there is a 50% risk of children from a heterozygous RhD-positive father being RhD-positive.[34] In the case of a heterozygous RhD-positive, or unknown, paternal genotype, the fetal antigen type should be assessed (by genetic testing of amniotic fluid cells or using cell-free fetal DNA in the maternal circulation).[34][35]​ In the case of an RhD-positive fetus, management involves fetal and maternal surveillance for signs of fetal anaemia and hydrops.

Quantitation of maternal antibody titre is performed serially to document worsening disease and identify the need for additional fetal testing and/or treatment. The American College of Obstetricians and Gynecologists states that a critical titre (titre associated with a significant risk for severe haemolytic disease of the fetus and newborn, and hydrops) is considered to be between 1:8 and 1:32 in most centres.[34] If the initial antibody titre is 1:8 or less, the patient may be monitored with titre assessment every 4 weeks.[34] However, serial titres are not adequate for monitoring fetal status when the mother has had a previously affected fetus or neonate.[34] In the UK, the Royal College of Obstetricians and Gynaecologists recommends anti-D antibodies should be measured every 4 weeks up to 28 weeks of gestation and then every 2 weeks until delivery, and referral to a fetal medicine specialist should occur if there are rising antibody levels, if the level reaches the specific threshold of >4 IU/mL, or if ultrasound features are suggestive of fetal anaemia.[52]​

In a centre with trained personnel and when the fetus is at an appropriate gestational age, Doppler measurement of peak systolic velocity in the fetal middle cerebral artery is an appropriate non-invasive means to monitor pregnancies complicated by RhD sensitisation.[34] Fetal ultrasound assessment is also employed.

The goal of fetal therapy is to correct severe anaemia, ameliorate tissue hypoxia, prevent (or reverse) fetal hydrops, and avoid fetal death.

If fetal middle cerebral artery flow or amniotic bilirubin levels are elevated, suggesting fetal anaemia, the fetus can be given intravascular intrauterine blood transfusions by a specialist at an institution equipped to care for high-risk pregnancies.

ACUTE

neonate with erythroblastosis

1st line – paediatric evaluation

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ACUTE
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neonate with erythroblastosis
1st line – 

paediatric evaluation

Neonates with erythroblastosis are immediately evaluated by a paediatrician to determine the need for exchange transfusion, phototherapy, or intravenous immunoglobulin.

Primary options

normal immunoglobulin human: consult specialist for guidance on dose

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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