Rhogam Redux

Before diving into this podcast, please check out our previous post for the basics on preventing Rh-D alloimmunization in the Emergency Department! 

Quick Review

Figure 1 - Description of Rhogam

Figure 1 - Description of Rhogam

Hemolytic Disease of the Fetus and Newborn (HDFN) is an alloimmune disease which develops in a fetus when a women’s immune system is sensitized, developing antibodies which cross the placenta and attack fetal RBCs. 

While there is a spectrum of the disease, in severe cases the fetus can ultimately develop hydrops fetalis which is often fatal.

As Emergency Physician’s we are classically taught that we can help to prevent HDFN by recognizing sensitizing events in Rh-negative women and subsequently providing RhoGAM. But which patients really need RhoGAM? The evidence seems to be lacking and recommendations are often inconsistent.

When discussing maternal sensitization what are we often referring to?

Figure 2 - Maternal sensitizing events

Figure 2 - Maternal sensitizing events

HDFN is most commonly triggered by the D antigen, expressed as part of the fetal red blood cell (RBC) membrane at 38 days. Mothers are exposed to the fetal Rh D antigen when barriers between fetal and maternal circulation (the syncytiotrophoblast and the cytotrophoblast) cease to function and fetal RBCs are lost into maternal circulation, this is called fetal-maternal hemorrhage (FMH). This antenatal mixing of fetal and maternal blood occurs frequently, even in asymptomatic women, and can lead to sensitization. While FMH is most common during labor, this can occur earlier in the pregnancy.

Recommendations regarding RhoGAM administration in early pregnancy have been inconsistent likely secondary to insufficient evidence. Threatened abortion is something not infrequently seen in the Emergency Department, yet a clear example of inconsistent national guidelines. Some national guidelines recommend against giving anti-D immune globulin to women with threatened pregnancy loss while others recommend RhoGAM should be given to a threatened miscarriage when vaginal bleeding is heavy, repeated, or associated with abdominal pain. So when should we be giving RhoGAM: threatened miscarriage, documented first-trimester loss, ectopic pregnancy or abdominal trauma in pregnancy? Dr. Taleghani, a NICU pharmacist at The University of Cincinnati Medical Center discusses this further with Adam Gottula, an Emergency Medicine intern, in our podcast!

Below are the recommendations discussed in the podcast:

ACEP Recommendations (originally published in 2003 with updated literature review in 2012): 

  • Recommendation was to administer 50 μg of anti-D immunoglobulin to Rh-negative women in all cases of documented first-trimester loss of established pregnancy to prevent Rh-D alloimmunization. 
  • There was also a level C recommendation to consider anti-D immunoglobulin use in cases of minor abdominal trauma. 
  • There was insufficient evidence to recommend for or against its use in treating threatened abortion or ectopic pregnancy. (1) 

ACOG recommendations:

  • Because of the higher risk of alloimmunzation, Rh D-negative women who have instrumentation for their miscarriage should receive Rh D immune globulin prophylaxis (RhoGAM)
  • Administration of Rh D immune globulin (RhoGAM) for all cases of ectopic pregnancy is recommended
  • Anti-D immune globulin is recommended for Rh d-negative women who experience antenatal hemorrhage after 20 weeks gestation
  • Anti-D immune globulin should be administered to Rh-D negative women who have experienced abdominal trauma
  • Anti-D immune globulin should be administered to Rh D-negative women who experience fetal death in the second or third trimester
  • Although the risk of alloimmunization is low, the consequence can be significant and administration of Rh D immune globulin should be considered in cases of spontaneous first-trimester miscarriage, especially those that are later in the first trimester. (2)

Cochrane review

“There are insufficient data available to evaluate the practice of anti-D administration in an unsensitised Rh-negative mother after spontaneous miscarriage. Thus, until high-quality evidence becomes available, the practice of anti-D Immunoglobulin prophylaxis after spontaneous miscarriage for preventing Rh alloimmunisation cannot be generalised and should be based on the standard practice guidelines of each country.” (3)

The NICE guidelines

Offer anti-D rhesus prophylaxis at a dose of 250 IU (50 micrograms) to all rhesus negative women who have a surgical procedure to manage an ectopic pregnancy or a miscarriage.

Do not offer anti-D rhesus prophylaxis to women who:

  • Receive solely medical management for an ectopic pregnancy or miscarriage or
  • Have a threatened miscarriage or
  • Have a complete miscarriage or
  • Have a pregnancy of unknown location.

Do not use a Kleihauer test for quantifying feto–maternal haemorrhage. (4)

Taming The SRU Approach to the undifferentiated female patient to limit risk of alloimmunization by fetal-maternal hemorrhage and appropriate RhoGAM use: 

Rhogam administration algorithm


  1. Hahn SA, Lavonas EJ, Mace SE, et al. Clinical policy: Critical issues in the initial evaluation and management of patients presenting to the emergency department in early pregnancy. Ann Emerg Med 2012; 60:381-390.
  2. “Practice Bulletin No. 181: Rh D Alloimmunization Prevention.” Obstetrics & Gynecology, vol. 130, no. 2, 2017, doi:10.1097/aog.0000000000002232.
  3. “Cochrane.” Anti-D Administration after Spontaneous Miscarriage for Preventing Rhesus Alloimmunisation | Cochrane, www.cochrane.org/CD009617/PREG_anti-d-administration-after-spontaneous-miscarriage-for-preventing-rhesus-alloimmunisation.
  4. “Ectopic Pregnancy and Miscarriage: Diagnosis and Initial Management.” Guidance and Guidelines | NICE, www.nice.org.uk/guidance/cg154/chapter/1-recommendations.

Post written by and Audio by Adam Gottula, MD

Editing, Peer Review, and Posting by Jeffery Hill, MD MEd