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RhIG crossing the placenta


QCDan

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Interesting case and was wondering if anyone else has seen this with Rhophylac.

mom is rh neg, RhIG is given, mom now has passive-D

baby has positive DAT on cordblood workup and an anti-D is eluted in the workup most likely from the RhIG that mom received.

in both cases the babies bilirubin was elevated slightly and the titer slowly decreased over time and eventually went to 0.

Just wanted to throw it out there since we have had 2 cases this year with this problem.

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We have had Routine Antenatal Anti-D Prophylaxis (RADDP) in the UK since August 2008 (National Institute for Health and Care Excellence (NICE).  Routine antenatal anti-D prophylaxis for women who are rhesus D negative.  Technology appraisal guidance (TA156).  Published date: 27 August 2008) - please excuse the word "rhesus"; they were told about this before publication, but they ignored all advice.

The following quote is from Qureshi H, Massey E, Kirwan D, Davies T, Robson S, White J, Jones J, Allard S.  BCSH guideline for the use of anti-D immunoglobulin for the prevention of haemolytic disease of the fetus and newborn.  Transfusion Medicine 2014; 24: 8-20 (doi: 10.1111/tme.12091),  "A direct antiglobulin test (DAT) on the cord blood sample is not routinely performed since it may be positive in a proportion of cases because of antenatal prophylaxis with anti-D Ig. However, a DAT should be performed if haemolytic disease of the newborn is suspected or anticipated because of a low cord blood haemoglobin concentration &/or the presence of maternal immune red cell antibodies."

From this, it can be seen that the phenomenon you describe is far from unusual, and extensive trials went on as far back as the early 1960's (Finn R, Clarke CA, Donohoe WTA, McConnell RB, Sheppard PM, Lehane D, Kulke W.  Experimental studies on the prevention of Rh haemolytic disease.  British Medical Journal 1961; 1: 1486-1490.  doihttp://dx.doi.org/10.1136/bmj.1.5238.1486, and no evidence was found that the fetus or newborn would be affected by this passive anti-D, even with a slightly raised bilirubin, which, is normal anyway, as HbF production is "switched off" and replaced by HbA production.

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We see a positive DAT from time to time that we attribute to RhoGAM, but no indication that any of these babies had elevated bilirubin levels from the anti-D immunoglobulin. There are a number of physiologic reasons for elevated bilirubin in neonates. If mom is a smoker, they have a lot of red cells on board that they don't need after birth. As Malcolm says, they are switching to HbA production. If the baby is not hydrated well the bili can become elevated, Etc... If anti-D has been identified in mother's sample and can be reasonably attributed to antenatal RhIG, we don't perform a titer on Rh positive baby cord blood samples unless there is some indication that something else is happening (strongly positive DAT or unexpectedly high bilirubin).

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  • 2 weeks later...

Good afternoon, has anyone else seen positive DATs on cords when baby is Rh positive and mother has received RHIG antenatally, but on admission for delivery has negative antibody screen?  

We have seen this on numerous occasions, but it is currently being called into question.

Is it safe to presume the DAT is positive due to RHIG or should we repeat the DAT on cord and screen on mom when this happens?

Is there a reason why the cord DAT would be more sensitive than the antibody screen?  We do all tube testing and use LISS as our enhancement.

Thank you!

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Hi tsanders0703, yes, this phenomenon is actually not that unusual.

The anti-D immunoglobulin in the maternal circulation will have a lower concentration than that in the foetal circulation because the IgG immunoglobulins are actively transported across the placenta.  However, because the maternal red cells do not express the D antigen, it will appear that the concentration of the anti-D immunoglobulin in the maternal circulation is higher than that in the foetal circulation, as that transported to the foetal circulation will be adsorbed onto the D antigen expressed on the foetal red cells; hence, there is detectable anti-D in the maternal plasma, but not necessarily in the foetal plasma, but the foetal red cells are DAT Positive.

As long as the mother has been shown not to have any atypical alloantibodies in her plasma during the pregnancy, then there really is no need to perform a DAT on the cord sample.  In the UK, this is actively discouraged by our Guidelines, if the mother is definitely known to have been given prophylactic anti-D immunoglobulin during her pregnancy.

Although the baby's red cells may well be DAT Positive, there really is no need to perform an elution, as the amount of anti-D adsorbed onto their red cells will be insufficient (by a considerable amount) to cause any clinically significant haemolysis (and, remember, there is always quite a drop in haemoglobin concentration anyway soon after birth).  If, however, the baby shows any CLINICAL SYMPTOMS of HDFN, then all tests should be performed, as the mother may have made an antibody against a low prevalence antigen that is expressed on both the paternal and baby's red cells that is not necessarily expressed on any of your screening or panel cells.

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Thank you Malcolm Needs!  Do you know of any reference books that can attest to this that I can show my higher ups?  

About a year ago we started reporting positive DAT “possibly due to RHIG” if baby is Rh Pos and mom received RHIG in the last 3 months, even if her screen is neg.  

My Medical Director and QA are now telling me that this isn’t possible and that we need to be repeating screen on mom if baby has positive DAT, but mom has neg screen (received RHIG in last 3 months and is ABO compatible).  I want my SOPs to be accurate, but I also don’t want to overdo it.

On the subject of not doing the DATs, I would be happy to get rid of the DATs on babies, but we are about to implement the Ortho Vision, and I’m not sure how to do a cord without the DAT.  The cord is run on the ABD Forward and Rev card and the only way that I can figure out to program this card without the reverse type is to do it with the DAT.  If you or anyone else knows how to program this and is willing to share, it would be greatly appreciated!

On the topic of getting rid of the DATs, if the baby is weak D positive, are you then doing the DAT to confirm the validity of the weak D result?  

Thank you for all of your expertise!

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I think you would probably find this in our UK Guidelines, if you put "BCSH Guidelines" or "BSH Guidelines" (they have recently changed their name) into your search engine, you should find Guidelines about anti-D immunoglobulin, and you should find it in there.  If not, get back to me and I will have a look in my text books.

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