I'm a little newer to the blood bank, so often need help understanding / reconciling our current policies - appreciate any help or insights (or references!)

Situation:

Mother has known alloantibody (a potentially clinically significant one). Baby is born and our testing shows negative antibody screen. Our current policy requires antigen-negative units for transfusion (with resultant AHG crossmatch) if maternal alloantibodies are present, but it doesn't say HOW LONG we need to give those antigen negative units.

Questions:

1. Is the use of the antigen negative units in this neonate with no detectable antibodies (negative screen) because of the possibility of "missing" low titers of maternal antibodies in baby? [I'm having trouble finding the REASON for this practice]

2. Am I correct in thinking that we could antigen type the neonate, and if we prove they lack the antigen in question then we could drop the requirement. [the baby in the actual case that brought this up had been transfused at the birth hospital, so we didn't attempt this]

3. How long does this antigen-negative requirement stand? Right now, our policy is being interpreted as lasting until the baby is 4 months old, but I really am not sure where that came from.

This is an "older" policy as I am no longer with this organization, but we have a large delivery unit and a 50+ bed level I NICU.

Here was our crossmatch policy for babies.

Couple of questions for clarification. What is the specificity of the known Alloantibody? "Baby is born and our testing shows negative antibody screen." Was this AB screen done on mom or baby? If on the baby, was a current ab screen performed on mom and if so what was the results? Was a DAT performed on the baby? If so, what was the result? If not, why not? Thanks

1 hour ago, John C. Staley said:

Couple of questions for clarification. What is the specificity of the known Alloantibody? "Baby is born and our testing shows negative antibody screen." Was this AB screen done on mom or baby? If on the baby, was a current ab screen performed on mom and if so what was the results? Was a DAT performed on the baby? If so, what was the result? If not, why not? Thanks

All great questions, but I would also ask, what is the baby's Hb/Hct requiring a transfusion, and why not test the baby's DNA for the gene encoding the antigen cognate to the maternal antibody?

15 minutes ago, Malcolm Needs said:

and why not test the baby's DNA for the gene encoding the antigen cognate to the maternal antibody?

Could I ask why?

The ab would be passive, if the screen is neg, and this test would take days to come back, what is the value?

Not saying you're wrong, just trying to learn.

In this case, it’s an anti-N, but I would have the same question (and potentially more important to answer) if this was an Rh, K, or other “more often significant” antibody.

For clarity:

mom: positive screen at referring hospital (we don’t have L&D) - anti N identified

baby: got some blood at birth NICU, transferred to us. We get the record of anti-N from outside. Our tests show: baby negative ab screen, baby negative DAT

We didn’t have anti-N reagent to antigen type baby (plus they had been transfused).

I don’t remember precisely the hemoglobin, but it was in a range appropriate for transfusion - baby had undergone a few procedures with blood loss. There was very low suspicion for ongoing hemolysis and prenatal course had been okay - mom had been monitored by high risk MFM OB due to the antibody, but no intrauterine transfusions had been needed.

20 hours ago, Cliff said:

Could I ask why?

The ab would be passive, if the screen is neg, and this test would take days to come back, what is the value?

Not saying you're wrong, just trying to learn.

The reason I said this (and I admit that I am being more than a little "Reference Laboratory Pedantic here) is because a very good friend of mine (Edmond Lee, who used to work at the NHSBT-North London Centre at Colindale, with such luminaries as Prof Dame Marcela Contreras, Dr Mahes de Silva and Martin Redman, amongst others, who described a case where the bay of a woman with an extremely strong anti-K,, where the baby's foetal K antigens were blocked by the maternal anti-K, and so tested as negative (Lee E, Redman M, Owen I. Blocking of fetal K antigens on RBC by maternal anti-K. Transfus Med 2009; 19(3):139-40. doi: 10.1111/j.1365-3148.2009.00917.x. Later, he reported the same sort of thing with a maternal anti-Fy(a) (Lee E, Cantwell C, Muyibi KO, Modasia R, Rowley M, New H. Blocking phenomenon occurs with murine monoclonal antibodies (anti-Fya) in a neonate with a positive direct antiglobulin test due to maternal anti-Fy(a). Blood Transfus 2015; 13: 672-674. doi: 10.2450/2015.0232-14.

Obviously, in both these cases, the maternal antibody was easily detectable, so not the same as the case being described by BullDawgPath, and, in both cases, the baby's DAT was positive, BUT, in both cases, antigen negative blood was required by the baby.

20 hours ago, BulldawgPath said:

In this case, it’s an anti-N, but I would have the same question (and potentially more important to answer) if this was an Rh, K, or other “more often significant” antibody.

For clarity:

mom: positive screen at referring hospital (we don’t have L&D) - anti N identified

baby: got some blood at birth NICU, transferred to us. We get the record of anti-N from outside. Our tests show: baby negative ab screen, baby negative DAT

We didn’t have anti-N reagent to antigen type baby (plus they had been transfused).

I don’t remember precisely the hemoglobin, but it was in a range appropriate for transfusion - baby had undergone a few procedures with blood loss. There was very low suspicion for ongoing hemolysis and prenatal course had been okay - mom had been monitored by high risk MFM OB due to the antibody, but no intrauterine transfusions had been needed.

It is incredibly rare for anti-N to be an alloantibody, unless the individual is M+N-, and also S-s-U-. This is because the amino acids that characterise the N antigen on the Glycophorin A molecule (leucine, serine, threonine, threonine, glutamic acid) are identical to the amino acids that characterise the 'N' antigen on the Glycophorin B molecule.

Is the lady of Black ethnicity by any chance? If not, to be N Negative AND 'N' Negative would be almost unique.

This suggests to me that the anti-N reported to be in the maternal circulation by the other hospital may well have been an auto-antibody, and would almost certainly be sub-clinical in its significance. In such a case, I would not bother with performing genotyping of the baby's N type. However, as far as Rh, K, etc, I would certainly suggest that antigen negative blood is given to the baby, and I certainly WOULD perform foetal genotyping (see my answer to Cliff above).

Yes - she is African-American - the anti-N is pretty well established in her case to be an alloantibody - she's had it for awhile.

I recognize in this case, that an anti-N is more than likely non-significant, so I was less worried about any issues here.

I guess my REAL question is how long do you keep providing antigen negative units, particularly when the baby's antibody screen is negative? The way our policy reads right now is vague - but has been interpreted as basically until 4 months of age, which seems long to me!

39 minutes ago, BulldawgPath said:

I guess my REAL question is how long do you keep providing antigen negative units, particularly when the baby's antibody screen is negative? The way our policy reads right now is vague - but has been interpreted as basically until 4 months of age, which seems long to me!

In that case, I would consider a genotype, as getting hold of M+ N-, S-s-U- fresh units is not going to be easy. That having been said, as you say yourself, anti-N is rarely clinically significant and, if it is not detectable in either the maternal circulation, or in the baby's circulation, I wouldn't worry too much about giving M+, N-, S-s-U- blood. BEAR IN MIND THOUGH, THIS WILL BE A CLINICAL DECISION, AND I AM NOT, AND NEVER HAVE BEEN, MEDICALLY QUALIFIED.

For acquired maternal IgG antibodies (which may also be transferred postnatally through breast milk), assessing the antibody specificity (AbS) in the newborn, as previously mentioned, appears to be a reasonable approach. In addition, the Direct Antiglobulin Test (DAT) remains key, and performing an elution is important (even if the DAT result is negative). In your case, the negative DAT suggests that either the anti-N antibody did not cross the placenta, possibly due to being a naturally occurring IgM, and/or the baby is N-negative.

Edited July 4Jul 4 by Arno

We might be the "Odd-Man-Out" - but, if the mom has an antibody and the DAT is negative on the cord sample, we don't test the plasma. If they order a neonate type and screen and the screen is negative, we don't give antigen negative units.............🙀................unless there is clinical evidence of hemolysis our Med Dir says it's warranted.

Anti-N does not cause hemolytic Transfusion reactions nor hemolytic disease of the newborn and fetus. So I would not give N negative blood in general, nor if the cross match is negative.

40 minutes ago, Neil Blumberg said:

Anti-N does not cause hemolytic Transfusion reactions nor hemolytic disease of the newborn and fetus. So I would not give N negative blood in general, nor if the cross match is negative.

I'm sorry Neil, but Geoff Daniels quotes some HTR's caused by anti-N reacting at 37oC, and one case of mild HDFN in a M+ N+ baby, where the mother was M+ N-, S-, s- Uvar, in the third edition of his book, Human Blood Groups.

"I'm sorry Neil, but Geoff Daniels quotes some HTR's caused by anti-N reacting at 37oC,"

These are, if I remember correctly, fairly ancient reports and I have never seen nor heard of a case of hemolytic transfusion reaction or HDFN due to anti-N despite having had hundreds of patients with anti-N in our service over the last half century. I've never heard of anyone else seeing one. So this is very possibly a case of old reports of hemolysis due to other causes (undetected antibodies for example). Methodology for antibody detection in the 1940s and 1950s, and even 1960s, was significantly less sensitive and accurate than currently. There are reports mentioned in Mollison and other comprehensive texts such as Daniels of hemolytic reactions due to antibodies (e.g., anti-P1, anti-Leb, etc.) that have never been reported in modern literature (the last 30-40 years). This makes me suspicious that these old reports are mistaken as to the cause of hemolysis.

If the mother has an anti-N and the infant is not hemolyzing, and the antibody is undetectable I would not transfuse N negative blood. If the infant is hemolyzing, that is another story, obviously. A positive DAT, hemolysis and anti-N in the mother would dictate prudence and transfusing N negative blood. But I will stand by my original comment, which is that anti-N almost never causes clinically significant hemolysis in transfusion recipients nor in affected fetuses. Absent clinical and laboratory evidence for anti-N causing the infant's anemia, there is no reason to transfuse N negative blood when the antibody is not detectable in the fetus/infant.

Edited July 8Jul 8 by Neil Blumberg

Arndt PA, Garratty G, Marfoe RA, Zeger GD.  An acute haemolytic transfusion reaction caused by an anti-P1 that reacted at 37 degrees C.  Transfusion 1998; 38(4): 373-377.  DOI: 10.1046/j.1537-2995.1998.38498257376.x.

Smith D, Aye T, Er LS, Nester T, Delaney M.  Acute hemolytic transfusion reaction due to anti-P1: a case report and review of institutional experience.  Transfus Med Hemother 2019; 46: 381-384.  Published online as DOI: 10.1159/000490897.

Irani MS, Figueroa D, Savage G.  Acute hemolytic transfusion reaction due to anti-Le^b.  Transfusion 2015; 55: 2486-2488.  DOI: 10.1111/trf.13178.

Delk AA, Gammon RR, Alvarez H, Benitez N, Bright F,  A hemolytic transfusion reaction caused by an unexpected Le^b antibody.  Laboratory Medicine 2021; 52: 303-306.  DOI:  10.1093/labmed/lmaa070.

Thanks Malcolm. Never say never :).

15 minutes ago, Neil Blumberg said:

Thanks Malcolm. Never say never :).

Love that!