What is the function of Rho(D) immune globulin (RhIG)?

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From the Guidelines

Rho D immune globulin prevents Rh sensitization in Rh-negative individuals exposed to Rh-positive blood by binding to any Rh-positive red blood cells that enter an Rh-negative person's circulation, preventing the immune system from recognizing these cells and developing antibodies against them. This is crucial in preventing hemolytic disease of the newborn in future pregnancies, as sensitization can lead to severe complications such as anemia and jaundice 1. The administration of Rho D immune globulin is particularly important in Rh-negative pregnant women who are carrying or have delivered an Rh-positive baby, as well as after miscarriages, abortions, ectopic pregnancies, or other events that might cause fetal-maternal bleeding.

Key Points

  • Rho D immune globulin is given to Rh-negative pregnant women at 28 weeks of pregnancy and again within 72 hours after delivery
  • It is also administered after miscarriages, abortions, ectopic pregnancies, or other events that might cause fetal-maternal bleeding
  • The standard dose is 300 mcg intramuscularly, though smaller doses may be used for early pregnancy losses
  • A study published in the American Journal of Obstetrics and Gynecology in 2024 found that data on the risks of alloimmunization after early pregnancy loss or induced abortion do not convincingly demonstrate the safety of forgoing RhIg 1

Administration Considerations

  • The only randomized controlled trial of antepartum RhIg for spontaneous abortion at 8 to 24 weeks of gestation demonstrated no sensitization events in 29 participants 1
  • Another observational study of 32 RhD-negative patients with an RhD-positive live birth following a spontaneous abortion demonstrated 1 sensitization event in a patient with spontaneous abortion and subsequent curettage at 16 weeks of gestation 1
  • These studies highlight the importance of administering Rho D immune globulin to prevent Rh sensitization, even in cases where the risk of alloimmunization may seem low.

From the FDA Drug Label

HyperRHO S/D Full Dose is used to prevent isoimmunization in the Rho(D) negative individual exposed to Rho(D) positive blood as a result of a fetomaternal hemorrhage occurring during a delivery of an Rho(D) positive infant, abortion (either spontaneous or induced), or following amniocentesis or abdominal trauma HyperRHO S/D Full Dose acts by suppressing the immune response of Rho(D) negative individuals to Rho(D) positive red blood cells.

Rho D immune globulin prevents isoimmunization in Rho(D) negative individuals exposed to Rho(D) positive blood. It suppresses the immune response to Rho(D) positive red blood cells, thereby reducing the risk of Rh hemolytic disease of the newborn. The administration of Rho(D) Immune Globulin (Human) within 72 hours of a full-term delivery of an Rho(D) positive infant by an Rho(D) negative mother reduces the incidence of Rh isoimmunization from 12%–13% to 1%–2% 2.

  • Key benefits:
    • Prevents isoimmunization in Rho(D) negative individuals
    • Suppresses immune response to Rho(D) positive red blood cells
    • Reduces risk of Rh hemolytic disease of the newborn
  • Administration: Within 72 hours of a full-term delivery of an Rho(D) positive infant by an Rho(D) negative mother 2.

From the Research

Rho D Immune Globulin Function

Rho D immune globulin, also known as RhIg or anti-D immunoglobulin, is used to prevent Rh immunization in RhD negative pregnant women carrying an RhD positive fetus. The main function of Rho D immune globulin is to:

  • Prevent anti-D alloimmunization in RhD negative women, which can lead to hemolytic disease of the fetus and newborn (HDFN) 3, 4
  • Rapidly remove the antigen by antibody overflow, and induce antibody-mediated immune suppression (AMIS) 4

Mechanism of Action

The exact immunological principle of Rho D immune globulin is not fully known, but it is assumed to work by:

  • Preventing the development of irregular antibodies against the RhD antigen 4
  • Removing the antigen from the maternal circulation, thereby preventing an immune response 4

Administration and Targeted Prophylaxis

Rho D immune globulin is administered to RhD negative pregnant women at risk of Rh immunization, including:

  • Antenatal prophylaxis, which can be targeted using noninvasive antenatal screening for fetal RHD status 5
  • Postnatal prophylaxis, which is typically administered to women who deliver an RhD positive newborn 3, 6

Special Considerations

In women with a serologic weak D phenotype, RhD genotyping is recommended to determine the molecular basis of the weak D phenotype and guide the need for Rh immunoprophylaxis 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

RhIg for the prevention Rh immunization and IVIg for the treatment of affected neonates.

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis, 2020

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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