Is RhIG mandatory in first trimester vaginal bleeding? That’s a negative.

The ED is packed, as usual, and the waiting room is filling up. One of your patients, a 28-year old woman with first trimester vaginal spotting, approaches you again. “Doc, what are we waiting for, again? When can I leave?”

“So far, all your results are reassuring. I’m sorry, we’re still waiting for one more blood test. We just want to make sure that, in case fetal blood has mixed with your own, your future pregnancies will be safe.”

You get a puzzled look, but have to move on. The next time you sit down to review her labs, you see the blood bank has determined she’s Rh(+). At last, your patient can be safely discharged. This straightforward case of threatened AB took far too long to dispo, but finally you can call for someone new to come in from the waiting room.

Unfortunately, this scenario plays out too often, in emergency departments across the country. Patients and providers are faced with prolonged length-of-stays and frustration because of extended lab turnaround times, all to determine rhesus status, to see if the patient should receive RhIG (commonly branded as RhoGAM).

At SAEM’s Annual Meeting this past June, we presented six months of retrospective data on just how much longer we’re waiting for blood types at our institution. It turns out, for our busy urban academic ED, we showed first-trimester patients with vaginal bleeding endured a length of stay 82 minutes longer than a cohort of women with similar age and acuity.

And, compared to first trimester patients with vaginal bleeding who had no blood type ordered (presumably, these patients had their type on file already), patients with a type order had a length of stay over two hours longer. Generalizing this data to our annual volume, we calculated that subtracting the blood type turnaround time would free up over 1100 extra bed-hours per year.

But of course, we have to wait for the blood type: we must determine if an injection of RhIG is necessary… right?

As we searched the literature on this topic, it became clear that our current practice has very little evidence to support it. Screening women in the ED with spontaneous first trimester bleeding for Rh status, and subsequent RhIG administration, is based on expert opinion, theoretical risks and extrapolations, as opposed to any proven risk.

The controversy comes from 50-year old data suggesting the minimum volume of blood needed to sensitize Rh(-) male volunteers is 0.1 mL, but the estimated quantity of feto-maternal transfusion in spontaneous abortion at 8 weeks is 0.33mL.

Trials and case reports of Rh sensitization were carried out in the era before routine ultrasound in pregnancy, so gestational ages are less certain (and the trials were poorly controlled, with more loss to followup). The only randomized trial was underpowered to detect benefit of RhIG, none of the 57 Rh(-) women with first trimester abortion in the trial went on to demonstrate immune sensitization.

ACOG guidelines make no specific recommendation for screening, or administration of RhIG, stating only “anti(D) immune globulin should be considered in threatened abortion.” (ACOG 1999)

Guidelines from professional societies in the UK and Australia have allowed for differing doses and indications for administration in times of RhIG shortage. Still, no reports of Rh sensitization in cases of spontaneous first trimester vaginal bleeding have emerged.

With all the confusion and different standards surrounding RhIG administration, it’s only prudent that we look at ways to deliver quality care in an efficient manner.

Fortunately, this is exactly what NQF has recently done. The National Quality Forum proposed (and ACEP endorsed) a quality measure by which US emergency departments would be measured.: that pregnant Rh negative patients who qualify should receive an injection of RhIG. Similarly to us, NQF reviewed the literature surrounding RhIG and determined that there was insufficient data to support the current standard of care. The quality measure excludes patients with spontaneous, non-ectopic vaginal bleeding or uncomplicated miscarriage with gestational age under 12 weeks.

Although the NQF has proposed a rational, evidence-based measure regarding the use of RhIG, the measure has not been without controversy. A recent article in Annals of Emergency Medicine by Griffey et. al detected a substantial performance gap in Rh testing and immunoglobulin administration in patients with a sensitizing event, in a single academic emergency department. Although the authors acknowledge the data and appropriateness of the NQF measure, they go on to suggest that if the performance gap cannot be closed, NQF should broaden the measure to screen all pregnant women that present to the ED and administer RhIG to all who are Rh negative:

“In general, although we should strive for evidence-based care, success in achieving standard practice is more likely when there are fewer exceptions to consider. In part for these reasons, because the direct evidence informing practice is not definitive and because it is our historical practice and teaching to do so, we chose to include first-trimester patients in our performance evaluation.”

It’s unusual that a scientific journal should publish a discussion advocating the science be disregarded, for the sake of expediency. This seems like an extreme solution to a problem that could be easily overcome through other means.

Shah et. al were able to show that over 97% of pregnant women presenting to an urban ED who claimed to “definitely” know their blood type and Rh status were correct, and not one woman in their cohort identified herself as Rh positive when she was actually Rh negative (all Rh negative women who were confident of their type correctly reported their Rh status).

And, as electronic charting becomes more common in EDs, a simple chart review may reveal a patient’s blood type, reducing redundant blood tests and expediting throughput. For patients new to your ED or institution, one can hope for robust integration with hospital records, or a regional health information organization.

Another option would be to simply talk to the patients about the potential risks of skipping the RhIG shot, the benefits of waiting for RH typing, and their availability for followup. We call patients back for culture results, so why not this? Especially since Rh positivity is relatively uncommon in most populations.
Considering the state of ED crowding, it doesn’t make sense to continue our current inefficient practice of Rh typing for first trimester bleeding, for the purpose of an intervention (RhIG) for which only a small fraction of patients qualify, and for which no benefit has ever been satisfactorily demonstrated.

Some believe that a common approach to all pregnant ED patients will prevent Rh sensitization in some, regardless of the vanishingly small or theoretical risks to other subgrounds. We would argue that perpetuating inefficient practice that disregards evidence is always undesirable. We should abide by the ACEP-endorsed NQF quality measure on RhIG administration, which in this case rewards efficient, evidence-based care.


RhIG & Men
It comes from men, and now at some trauma centers, it goes back into them

It should come as no surprise that there aren’t a lot of women with monoclonal Rh immunoglobulin around – in this case, medicine is a victim of its own success in preventing immunosensitization.  

So where does RhIG come from? It turns out, the usual means of producing monoclonal antibodies have proven either too expensive or not effective enough. So, Rh negative male volunteers are still recruited. These men receive transfusions of otherwise-matched Rh+ blood, and generate the antibodies. Their blood, containing the Rh immunoglobulins, is then collected, screened for viruses, concentrated, and purified, and finds its way to EDs and healthcare facilities everywhere.

Giving Rh+ blood to males is also practiced in trauma centers, as type O negative blood is rare and O+ blood will do for men, who don’t need to worry about attacking a future fetus growing inside them.

But men who receive type O+ blood do need to worry about “trauma recidivism” which is to say, needing another type O+ transfusion down the line – that second transfusion could cause a hemolytic reaction. Thus, centers that transfuse O+ blood have adopted the practice of giving RhIG alongside it. It’s breathtaking, in a way – a landmark achievement in preventative medicine is being deployed in an almost cynical fashion to protect repeat offenders in trauma.

Raviraj Patel is a PGY-3 EM Resident and Nicholas Genes is Assistant Professor in the Department of Emergency Medicine at Mount Sinai School of Medicine


  • Miraflor E, et al. Emergency uncrossmatched transfusion effect on blood type alloantibodies JTrauma 2012;72:48-53.
  • The Trauma Professional’s Blog accessed July 9, 2012.
  • National Quality Forum #0652: “Rh immunoglobulin (Rhogam) for Rh negative pregnant women at risk of fetal blood exposure.” Most Recent Update: September 22, 2011. Date of Access: June 1, 2012.
  • Hannafin B, Lovecchio F, et al. Do Rh-negative women with first trimester spontaneous abortions need Rh immune globulin? Am J Emerg Med. 2006; 487-489.
  • Griffey RT, Chen BC, Krehbiel NW. Performance in appropriate Rh testing and treatment with Rh immunoglobulin in the emergency department. Ann Emerg Med. 2012: 285-93
  • Wittels KA, Pelletier AJ, et al. US emergency department visits for vaginal bleeding during early pregnancy, 1993-2003. Am. J. Obstet. Gynecol. 2008;198:523
  • Reid ME, Lomas-Francis C. The Blood Group Antigen Facts Book. New York, NY: Academic Press, 1997
  • Royal College of Obstetricians and Gynaecologists. Clinical green top guidelines: use of anti-D immunoglobulin for Rh prophylaxis (Revised May, 2002).
  • Parker J, Wray J, Gooch A, et al, for the British Committee for Standards in Haematology. Guidelines for the use of prophylactic anti-D immunoglobulin. June 2008.
  • Jabara S, Barnhart KT. Is Rh immune globulin needed in early first-trimester abortion? A review. Am J Obstet Gynecol. 2003 Mar;188:623-7.
  • Australian Government National Health and Medical Research Council. Guidelines on the prophylactic use of Rh D immunoglobulin (anti-D) in obstetrics: Revised, 2003. 


# MS-IVLauren Westafer 2012-10-26 13:40
Great article with well stated solutions! I've been excited about more literature and enthusiasm on this topic since I heard a SMARTEM podcast on this very issue. One point of clarification - Rh positivity is very common in our population in the US juxtaposed with a relatively uncommon Rh negativity in our population (perhaps it's a typo or I'm misinterpreting the sentence).

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