Malcolm Needs

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-Leb.  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 Leb antibody.  Laboratory Medicine 2021; 52: 303-306.  DOI:  10.1093/labmed/lmaa070.

Love that!

Thanks Malcolm. Never say never :).

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-Leb.  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 Leb antibody.  Laboratory Medicine 2021; 52: 303-306.  DOI:  10.1093/labmed/lmaa070.

"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.

That's OK. Pass (yay!) or fail, either way, it's always a learning opportunity.

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.

Good morning, Malcom. Thanks for your reply- she is 61 yrs old and KNeg. I agree also with your approach, but we also have lots of patients with chronic anemias on transfusion support for whom we aren't giving K Neg. Maybe the dr. is just being more proactive in this case.

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.

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.

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.

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).

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).

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?

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.

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?

What? All this time I have been using the wrong stuff! Ha! SPELL CHECK IS NOT YOUR FRIEND! 🤣🤣🤣🤣

Um, sorry Jason, but I think you mean Dithiothreitol (DTT), rather than Dichlorodiphenyltrichloroethane (DDT)!!!!!!!

Um, sorry Jason, but I think you mean Dithiothreitol (DTT), rather than Dichlorodiphenyltrichloroethane (DDT)!!!!!!!

Um, sorry Jason, but I think you mean Dithiothreitol (DTT), rather than Dichlorodiphenyltrichloroethane (DDT)!!!!!!!

Thanks to the recent publications sent by @Malcolm Needs I knew this one! 😊

AGREED - and killing the patient in some circumstances!!!!!!!!!!!!!!!!!!

AGREED - and killing the patient in some circumstances!!!!!!!!!!!!!!!!!!

I just answered this question.

My Score PASS  

I agree Darin, it is almost certainly a dilutional effect, BUT, it could also be the effect of a soluble antigen (obviously not within the Duffy Blood Group System). If the antibody had a specificity within, for example, the Lewis Blood Group System, or the Chido/Rodgers Blood Group System, the antigen in the plasma could well adsorb out the circulating antibody. That having been said, this explanation is FAR less likely than your suggestion of the dilutional effect.