Does an Rh negative mother require RhoGAM (Rho(D) immune globulin) with each episode of bleeding or is one dose per pregnancy sufficient?

From the Guidelines

Rh negative mothers require RhoGAM (Rho(D) immune globulin) after each episode of bleeding during pregnancy, as well as at 28 weeks gestation and within 72 hours after delivery if the baby is Rh positive, to prevent the formation of antibodies against Rh positive blood. The standard protocol for RhoGAM administration includes a preventive dose at 28 weeks gestation and another dose within 72 hours after delivery if the baby is Rh positive 1. Additionally, RhoGAM should be administered after any bleeding episode during pregnancy, including miscarriage, ectopic pregnancy, abortion, amniocentesis, chorionic villus sampling, or any trauma that could cause fetomaternal hemorrhage 1. This repeated administration is necessary because each bleeding event potentially exposes the mother to the baby's Rh positive blood cells, which could trigger antibody production. Without adequate RhoGAM after each exposure, the mother may develop antibodies against Rh positive blood, which could cause hemolytic disease in future Rh positive pregnancies. The dosage typically depends on the gestational age and type of bleeding, with a mini-dose (50 μg) often used for early pregnancy events and a full dose (300 μg) for later pregnancy events or delivery 1. It is essential to prioritize the administration of RhoGAM after each bleeding episode to minimize the risk of alloimmunization and ensure the best possible outcomes for the mother and future pregnancies 1. Key considerations in the administration of RhoGAM include:

• Gestational age at the time of bleeding
• Type and severity of bleeding
• Availability of RhoGAM and potential need for substitution with an equivalent product
• Patient-specific factors, such as history of previous RhoGAM administration and presence of anti-Rh antibodies. In cases where RhoGAM is not available, it is crucial to prioritize its administration to postpartum patients and antenatal patients at later gestational ages 1. By following the standard protocol for RhoGAM administration and prioritizing its use after each bleeding episode, healthcare providers can minimize the risk of alloimmunization and ensure the best possible outcomes for Rh negative mothers and their babies.

From the FDA Drug Label

If HyperRHO S/D Full Dose is administered antepartum, it is essential that the mother receive another dose of HyperRHO S/D Full Dose after delivery of an Rho(D) positive infant. HyperRHO S/D Full Dose should be administered within 72 hours to all nonimmunized Rho(D) negative women who have undergone spontaneous or induced abortion, following ruptured tubal pregnancy, amniocentesis or abdominal trauma unless the blood group of the fetus or the father is known to be Rho(D) negative.

An Rh negative mother requires more than one dose of RhoGAM (Rho(D) immune globulin) per pregnancy.

• A dose is needed after delivery of an Rho(D) positive infant if a dose was given antepartum.
• A dose is also needed within 72 hours after any episode of bleeding, such as spontaneous or induced abortion, ruptured tubal pregnancy, amniocentesis, or abdominal trauma, unless the blood group of the fetus or the father is known to be Rho(D) negative 2.

From the Research

RhoGAM Administration in Rh-Negative Mothers

• The administration of RhoGAM (Rho(D) immune globulin) to Rh-negative mothers is crucial to prevent Rh alloimmunization, which can lead to hemolytic disease of the fetus and newborn in subsequent pregnancies 3, 4.
• According to guidelines, RhoGAM should be administered to Rh-negative mothers at 28 weeks of gestation and shortly after delivery, with additional doses given in cases of fetomaternal hemorrhage (FMH) greater than 15 mL of fetal red blood cells 3.
• In cases of massive FMH, high-dose RhoGAM may be required, with dosing calculated based on the amount of fetal blood in the maternal circulation 5, 6.
• The use of RhoGAM in early pregnancy, such as after spontaneous or induced abortion, is also recommended, although the risk of Rh sensitization is considered low if the gestation is less than 12 weeks 7.

Dosing Recommendations

• The standard dose of RhoGAM is 300 micrograms, which is sufficient to cover FMH of up to 15 mL of fetal red blood cells 3.
• In cases of larger FMH, additional doses of RhoGAM may be required, with 10 micrograms of RhoGAM given for every additional 0.5 mL of fetal red blood cells 3.
• High-dose RhoGAM, up to 4800 micrograms, may be required in cases of massive FMH, such as in the case of a 15-year-old girl who presented with intrauterine fetal demise and was found to have nearly 460 mL of fetal blood in the maternal circulation 6.

Special Considerations

• Women with molecularly defined weak D types or Asian-type DEL (c.1227G>A) may not require RhoGAM, as they are unlikely to produce alloanti-D when exposed to fetuses with D-positive red cells 4.
• RhoGAM administration should be individualized based on the specific clinical scenario, taking into account the risk of FMH and the amount of fetal blood in the maternal circulation 3, 5, 6.