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

unsensitized RhD-negative mother

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Rho(D) immune globulin

Routine prenatal administration: Rho(D) immune globulin administered whether fetal blood type is unknown, or known to be RhD-positive. Single dose at 28 weeks’ gestation (either intravenously or intramuscularly).[21]​ Some guidelines recommend a single dose at around 28 weeks, or two doses at around 28 and 34 weeks of gestation.​[27][34][44]

Routine postpartum administration: Rho(D) immune globulin administered (either intravenously or intramuscularly) in women who have given birth to Rh-positive infants within 72 hours of delivery.[21]​​​​[27][44] The size of fetomaternal hemorrhage should be assessed, and further doses of Rho(D) immune globulin administered if required.[21][34]​​

The dose can vary depending on local guidelines, and factors such as brand of Rho(D) immune globulin.

Primary options

Rho(D) immune globulin: consult specialist for guidance on dose

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additional Rho(D) immune globulin

Treatment recommended for ALL patients in selected patient group

Additional Rho(D) immune globulin administration should not be given routinely following spontaneous miscarriage or abortion in the first trimester.[21]​ However, it may be considered on an individual basis, according to patient preferences.[21][25]​​

Rho(D) immune globulin administration is recommended following pregnancy termination (either medical or surgical); or fetal death in the second or third trimester.[21][25]

Dose should be given within 72 hours of occurrence.[27][34] The dose can vary depending on local guidelines, and factors such as brand of Rho(D) immune globulin.

For sensitizing events occurring after 20 weeks of pregnancy, size of fetomaternal hemorrhage should be assessed, and further doses of Rho(D) immune globulin administered if required.[34][49]​​ 

Guidelines for Rho(D) immune globulin administration vary; follow local protocols.

Primary options

Rho(D) immune globulin: consult specialist for guidance on dose

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additional Rho(D) immune globulin

Treatment recommended for ALL patients in selected patient group

Rho(D) immune globulin administration is recommended following all cases of ectopic pregnancy.[21] 

Dose should be given within 72 hours of identification.[21][27][34] The dose can vary depending on local guidelines, and factors such as brand of Rho(D) immune globulin.

Guidelines for Rho(D) immune globulin administration vary; follow local protocols.

Primary options

Rho(D) immune globulin: consult specialist for guidance on dose

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additional Rho(D) immune globulin

Treatment recommended for ALL patients in selected patient group

Additional Rho(D) immune globulin is advised to be administered in all molar pregnancies (due to the difficulty in differentiating between complete and partial forms).[21][44] 

Dose should be given within 72 hours of identification.[27][34] The dose can vary depending on local guidelines, and factors such as brand of Rho(D) immune globulin.

Primary options

Rho(D) immune globulin: consult specialist for guidance on dose

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additional Rho(D) immune globulin

Treatment recommended for ALL patients in selected patient group

Additional Rho(D) immune globulin administration is recommended following invasive diagnostic procedures such as chorionic villus sampling or amniocentesis.[21]

Dose should be given within 72 hours of occurrence.[27][34] The dose can vary depending on local guidelines, and factors such as brand of Rho(D) immune globulin.

If carried out after 20 weeks of pregnancy, size of fetomaternal hemorrhage should be assessed, and further doses of Rho(D) immune globulin administered if required.[34][49] 

Primary options

Rho(D) immune globulin: consult specialist for guidance on dose

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additional Rho(D) immune globulin

Treatment recommended for ALL patients in selected patient group

Additional Rho(D) immune globulin is recommended for prenatal hemorrhage after 20 weeks of gestation, and abdominal trauma.[21]

Dose should be given within 72 hours of occurrence.[27][34] The dose can vary depending on local guidelines, and factors such as brand of Rho(D) immune globulin.

Consider quantitative testing for fetomaternal hemorrhage 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 previa with bleeding).[27]​ Administer further doses of Rho(D) immune globulin if required.[34]

Primary options

Rho(D) immune globulin: consult specialist for guidance on dose

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additional Rho(D) immune globulin

Treatment recommended for ALL patients in selected patient group

Additional Rho(D) immune globulin administration is recommended following external cephalic version.[21]​ Quantitative testing for fetomaternal hemorrhage may also be considered.[27]

Dose should be given within 72 hours of occurrence.[27][34] The dose can vary depending on local guidelines, and factors such as brand of Rho(D) immune globulin.

Primary options

Rho(D) immune globulin: consult specialist for guidance on dose

sensitized RhD-negative mother

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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 sensitized, and specialist obstetric advice should be sought.[49] Rh immunoprophylaxis is no longer given.[32]

The initial management of an RhD-sensitized 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.[32] 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).[32][33]​ In the case of an RhD-positive fetus, management involves fetal and maternal surveillance for signs of fetal anemia and hydrops. 

Quantitation of maternal antibody titer 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 titer (titer associated with a significant risk for severe hemolytic disease of the fetus and newborn, and hydrops) is considered to be between 1:8 and 1:32 in most centers.[32] If the initial antibody titer is 1:8 or less, the patient may be monitored with titer assessment every 4 weeks.[32] However, serial titers are not adequate for monitoring fetal status when the mother has had a previously affected fetus or neonate.[32] 

In a center 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 noninvasive means to monitor pregnancies complicated by RhD sensitization.[32] Fetal ultrasound assessment is also employed.

The goal of fetal therapy is to correct severe anemia, 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 anemia, 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

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pediatric evaluation

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

Primary options

immune globulin (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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