L.C.H.

I would be interested in knowing how many antenatal RHIG doses the mother received. While it is possible for RHIG to cross the placenta and cause HDFN, seems to be extremely rare. The probability increases with each antenatal dose. That said, I agree with you that the baby's own cells should have sequestered any residual RHIG in circulation though I probably would not change my policy. I would just document the deviations when necessary.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877609/

Just curious but does the baby have a positive DAT due to the RhIG?  Is the anti:D demonstrable in the baby?  

Yes John,  With higher dose anti-D immunoglobulin, the DAT of a D Positive baby is quite often positive.  In the UK it is now quite common to give a dose of 1, 500 IU of anti-D immunoglobulin at 28 weeks of gestation and, as a result, many babies have a positive DAT, but I have never heard of clinically significant HDFN as a result,  Physiological jaundice is also quite common in newborns, whether the mother was given anti-D immunoglobulin or not, and whether the baby is D Positive or D Negative.

OK, follow-up as promised with results of the D chip - and I have some reading up to do on these.
Overall predicted RhD phenotype: D+ (weak partial)
Alleles:
- RHD*weak partial 4.0  encodes p.201Arg and p.223Val
- Hybrid RHD*D111a-CE(4-7)-D does not encode D but encodes partial C as part of r'S haplotype
 
The report includes a reference: "Experience with RHD*weak D type 4.0 in the USA," Blood Transfusion 2018:6: 1-3. 

OK, follow-up as promised with results of the D chip - and I have some reading up to do on these.
Overall predicted RhD phenotype: D+ (weak partial)
Alleles:
- RHD*weak partial 4.0  encodes p.201Arg and p.223Val
- Hybrid RHD*D111a-CE(4-7)-D does not encode D but encodes partial C as part of r'S haplotype
 
The report includes a reference: "Experience with RHD*weak D type 4.0 in the USA," Blood Transfusion 2018:6: 1-3. 

OK, follow-up as promised with results of the D chip - and I have some reading up to do on these.
Overall predicted RhD phenotype: D+ (weak partial)
Alleles:
- RHD*weak partial 4.0  encodes p.201Arg and p.223Val
- Hybrid RHD*D111a-CE(4-7)-D does not encode D but encodes partial C as part of r'S haplotype
 
The report includes a reference: "Experience with RHD*weak D type 4.0 in the USA," Blood Transfusion 2018:6: 1-3. 

I also should get up earlier to contribute! thank you all for the suggestions!
In response to some of the ideas -  her pregnancy loss end of last year and surrounding OB care was entirely through my institution, and I know we didnt give her any RhIg of any sort. Could find no evidence of ITP (handful of CBCs over months have been dead normal), no evidence of any underlying autoimmune disorder. No evidence of getting IVIG or any other antibody-based treatment. The only possible autoimmune trigger I recognized was the strep throat, but that's a long shot and anyhow she was promptly treated.  And we don't use gel.
Overnight we came up with some of the same ideas as y'all - warm auto with anti-D specificity, an anti-LW, or a D antigen variant. 
Just hearing from the manager we ran her against some O negative cord cells this morning; does not look like an anti-LW. We are opting to use what is left of the sample to send to reference for the D chip. I'll definitely update once we have more info!

I also should get up earlier to contribute! thank you all for the suggestions!
In response to some of the ideas -  her pregnancy loss end of last year and surrounding OB care was entirely through my institution, and I know we didnt give her any RhIg of any sort. Could find no evidence of ITP (handful of CBCs over months have been dead normal), no evidence of any underlying autoimmune disorder. No evidence of getting IVIG or any other antibody-based treatment. The only possible autoimmune trigger I recognized was the strep throat, but that's a long shot and anyhow she was promptly treated.  And we don't use gel.
Overnight we came up with some of the same ideas as y'all - warm auto with anti-D specificity, an anti-LW, or a D antigen variant. 
Just hearing from the manager we ran her against some O negative cord cells this morning; does not look like an anti-LW. We are opting to use what is left of the sample to send to reference for the D chip. I'll definitely update once we have more info!

I also should get up earlier to contribute! thank you all for the suggestions!
In response to some of the ideas -  her pregnancy loss end of last year and surrounding OB care was entirely through my institution, and I know we didnt give her any RhIg of any sort. Could find no evidence of ITP (handful of CBCs over months have been dead normal), no evidence of any underlying autoimmune disorder. No evidence of getting IVIG or any other antibody-based treatment. The only possible autoimmune trigger I recognized was the strep throat, but that's a long shot and anyhow she was promptly treated.  And we don't use gel.
Overnight we came up with some of the same ideas as y'all - warm auto with anti-D specificity, an anti-LW, or a D antigen variant. 
Just hearing from the manager we ran her against some O negative cord cells this morning; does not look like an anti-LW. We are opting to use what is left of the sample to send to reference for the D chip. I'll definitely update once we have more info!

I also should get up earlier to contribute! thank you all for the suggestions!
In response to some of the ideas -  her pregnancy loss end of last year and surrounding OB care was entirely through my institution, and I know we didnt give her any RhIg of any sort. Could find no evidence of ITP (handful of CBCs over months have been dead normal), no evidence of any underlying autoimmune disorder. No evidence of getting IVIG or any other antibody-based treatment. The only possible autoimmune trigger I recognized was the strep throat, but that's a long shot and anyhow she was promptly treated.  And we don't use gel.
Overnight we came up with some of the same ideas as y'all - warm auto with anti-D specificity, an anti-LW, or a D antigen variant. 
Just hearing from the manager we ran her against some O negative cord cells this morning; does not look like an anti-LW. We are opting to use what is left of the sample to send to reference for the D chip. I'll definitely update once we have more info!

I also should get up earlier to contribute! thank you all for the suggestions!
In response to some of the ideas -  her pregnancy loss end of last year and surrounding OB care was entirely through my institution, and I know we didnt give her any RhIg of any sort. Could find no evidence of ITP (handful of CBCs over months have been dead normal), no evidence of any underlying autoimmune disorder. No evidence of getting IVIG or any other antibody-based treatment. The only possible autoimmune trigger I recognized was the strep throat, but that's a long shot and anyhow she was promptly treated.  And we don't use gel.
Overnight we came up with some of the same ideas as y'all - warm auto with anti-D specificity, an anti-LW, or a D antigen variant. 
Just hearing from the manager we ran her against some O negative cord cells this morning; does not look like an anti-LW. We are opting to use what is left of the sample to send to reference for the D chip. I'll definitely update once we have more info!

I also should get up earlier to contribute! thank you all for the suggestions!
In response to some of the ideas -  her pregnancy loss end of last year and surrounding OB care was entirely through my institution, and I know we didnt give her any RhIg of any sort. Could find no evidence of ITP (handful of CBCs over months have been dead normal), no evidence of any underlying autoimmune disorder. No evidence of getting IVIG or any other antibody-based treatment. The only possible autoimmune trigger I recognized was the strep throat, but that's a long shot and anyhow she was promptly treated.  And we don't use gel.
Overnight we came up with some of the same ideas as y'all - warm auto with anti-D specificity, an anti-LW, or a D antigen variant. 
Just hearing from the manager we ran her against some O negative cord cells this morning; does not look like an anti-LW. We are opting to use what is left of the sample to send to reference for the D chip. I'll definitely update once we have more info!

All of the above are excellent suggestions. I will have to get up earlier to contribute.

Auto-anti-D is more common that a lot of people think, but I am NOT saying that is what this is - just that it may be.
It could also be that the D antigen of the individual is a Partial D Type, such as Partial D Type III, that would react like a "normal D" (in fact, it would have slightly elevated expression of the D antigen), but who could easily produce an allo-anti-D (and there could also be an auto-antibody present, accounting for the positive DAT).
In addition, particularly as the DAT is positive, the actual specificity of the antibody in the individual's plasma/serum could be an auto-anti-LW, that would mimic an anti-D.  This could be resolved by testing the antibody against a few group O, D Negative cord red cells, which would give fairly strong reactivity.

In any case, I would send a sample to a Reference Laboratory to ascertain the true specificity of the antibody, but also, as Ensis01 says, for molecular characterisation of the RHD gene (and do not forget to tell them the ethnic background of the individual, as this will make their lives so much easier).
Finally (for now, unless anything else springs to mind), please would you keep us informed of the outcome and results?  THANK YOU; an interesting case.

I would send out for molecular characterization of the D, and give O neg

Does the patient have ITP? Is it possible that she is receiving WinRHO (same as RHIG) for ITP? Does she have a low platelet count. I haven't seen this situation in several years but there was a time when patients with ITP who were rh pos would be treated with WinRHO (as long as they had their spleen). It would present as this very scenario you are describing.
Another possibility is anti-Lw?

Here are some thoughts 
1. Prophylatic anti-D given after pregnacy loss despite her D pos type and not communicated further (but sounds like the event is too old to support this option right?)
2. Can be an anti-LW instead which looks like auto anti-D (reacting stronger with D pos cells)
3. Other blood derived product given (e.g. IVIG) containing anti-D but the reaction strentgh does not support this hypothesis
4. D variants alloimmunized during first pregnancy with D pos fetus
 

I don't know if this will help or not.  I talk a bit about anti-D prophylaxis towards the end, and why it sometimes fails.  If it doesn't help, just ignore it!!!!!!!
In Depth Lecture on Alloimmune Haemolytic Disease of the Foetus and Newborn HDFN.pptx

OK i dont really understand this, but i asked for more specifics - and our backup computers are evidently attached to the network but in a weird limited fashion where they get a solitary incoming dump every four hours, of BB data, but otherwise do not receive network activity, and have no "outgoing" channel. when we were hacked, one was due for a dump and got hacked, the other was instantly quarantined off-line and so had almost all (except the last few hours worth) of BB data.
also was just told it is also now stashed in some quarantined part of the cloud?  this is waaaay over my head in terms of IT though. sorry i cant explain it any better :-(

OK i dont really understand this, but i asked for more specifics - and our backup computers are evidently attached to the network but in a weird limited fashion where they get a solitary incoming dump every four hours, of BB data, but otherwise do not receive network activity, and have no "outgoing" channel. when we were hacked, one was due for a dump and got hacked, the other was instantly quarantined off-line and so had almost all (except the last few hours worth) of BB data.
also was just told it is also now stashed in some quarantined part of the cloud?  this is waaaay over my head in terms of IT though. sorry i cant explain it any better :-(

An excellent discussion point. I think many others have similar questions and concerns. The have been several other threads on this forum with similar subject matter.
As an Old Fart, I feel obliged to spout some (un-referenced) history. Most of the original work on clinical significance of antibodies in pregnancies was done in the absence of potentiators and definitely before the use of (semi)automated test systems. I think it was a "saline-IAT" using 22% albumin (BSA) as a diluent. Most of those antibodies were anti-D, for obvious reasons. There's not much out there in the literature in terms of controlled or organized studies regarding other specificities. There are a fair number of one-of-a-kind case studies, but most of the stuff is retrospective analysis of data. Basically, other than anti-D, nobody really knows what an antibody titer means, but as Ensis01 suggests, detecting a change in titer (increase) may be more important.
In an era when basic tube shaking is going away, it only makes sense (we have no other option) to convert to the new techniques and equipment, but I suspect that it has the potential to further confuse an issue which already has enough confusion to (dis)satisfy everyone. I don't envy anyone handling this hairball.
As a last thought...the high-powered potentiators (and techniques) used today don't reflect what's going on in vivo. Arguably, if one ignored the 22% BSA diluent, the saline-IAT is a better mimic of the in vivo scenario.

We tell our clinicians to do exactly that, yes. Likely it won't turn into an anaphylactic event, but it could, so STOP and initiate a transfusion workup. Give benadryl and watch the patient.
For future transfusions, pre-treat with benadryl - even though it's likely a response to that one specific donor's plasma proteins, and a bag from a different donor may not provoke a reaction.

Cannot post the entire article due to copyright restrictions, but most institutions have access to NEJM through their library. If not, shoot me an email at neil_blumberg@urmc.rochester.edu and I'll send along the .pdf.
If you are transfusing 40-60 platelets a day, giving ABO identical to group O and A individuals should be relatively easy.  When patients are changing  ABO blood group it becomes more difficult. We avoid transfusion ABO antigen and/or antibody that is incompatible with either original recipient type or donor type.  Usually means washed group O red cells and platelets.  That's the bad news. It does require time and effort, and as you say, med techs are in short supply.  Here's the good news. If you transfuse ABO identical or washed compatible platelets you will use between 30-50% fewer platelets per patient, increasing your supply and decreasing your cost/problems. You will also use next to no HLA matched platelets (we used 3 out of 6,000 one recent year), you will have fewer febrile and allergic transfusion reactions, you will have fewer red cell as well as HLA antibodies made in recipients, and you may reduce TRALI and TACO.  Obviously you have to have universal leukoreduction to start with.  Selective leukoreduction misses about 50% of the  patients who will become refractory, probably due to missed or delayed diagnosis of hematologic malignancy, aplastic anemia, etc.  But the big attraction is you will have less bleeding, although that mainly affects the patients and the docs and nurses at the bedside.  

When you transfuse ABO major incompatible, which seems to be the default due to fear of hemolysis from minor incompatible, you don't get any increments, you use lots of platelets and the patients bleed more. (see references below)  Bleeding causes lots of harm, but also impacts the blood transfusion service for obvious reasons.  So figure out a way to start giving patients with aplastic anemia and acute myeloid leukemia who are newly diagnosed only ABO identical platelets and that will be a great start for the patients and the transfusion service.  Those patients will bleed less, need fewer platelet transfusions, have fewer transfusion reactions, will not have positive DATs, and will likely survive their hospitalization and disease at higher rates if our experience is typical.
And if you cannot give ABO identical or washed platelets free of incompatible cellular and soluble antigen and free of incompatible ABO antibody, start out with minor incompatible platelets (e.g., O to A) rather than ABO major incompatible (e.g., A to 0).  The risks of hemolysis are not negligible (about 1 in 800) but are less serious and severe than having life threatening bleeding or refractoriness which occur more rapidly with ABO major incompatible in all likelihood.  There's a ton of antibody that is incompatible with antigen transfused when we give A platelets to O recipients which means each antigen winds up with a ton of antibody making huge immune complexes.  When we  transfuse antibody incompatible we are transfusing a small amount of antibody into a recipient with huge amounts of antigen, so the size and number of immune complexes is probably smaller. These are my best guesses that we've been making exactly the wrong decision when we give ABO mismatched platelets. Best to avoid any, but major mismatched provides no hemostasis, minimal to no increment and is associated with increased bleeding mortality in the study from Columbia (David Roh and colleagues https://pubmed.ncbi.nlm.nih.gov/33649761/).  But ABO identical is not that hard for larger centers for the 85% of patients who are group O or A.  You just have to start small, get the hang of it, and then extend to other blood groups and other diseases than leukemia, MDS and aplastic anemia (including transplants, particularly allo--transplants). All those tables of how to select ABO mismatched platelets for transplant recipients are well intentioned but scientifically without evidence.  Avoid infusing incompatible antigen and antibody as much as possible, and delay transfusion when ABO identical will be available within hours.  Give priority to patient well being over inventory management. Give reduced doses, which work just as well.  Get a Terumo or Haemonetics washing device and wash with PAS. It's a big set of changes, but neither terribly expensive nor rocket science. The dogmas and expert opinion about universal leukoreduction and ABO matching of transfusions are now proven to be tragically mistaken.
 
https://www.ashclinicalnews.org/news/from-the-blood-journals/written-in-blood/outcomes-abo-incompatible-platelet-transfusions-patients-intracerebral-hemorrhage/
https://pubmed.ncbi.nlm.nih.gov/11399821/
https://pubmed.ncbi.nlm.nih.gov/21414009/

Research letter in NEJM describes our findings.  https://www.nejm.org/doi/full/10.1056/NEJMc2034764?fbclid=IwAR1BQRvpaHBAMDaHxCPY07xBjPQHlIHoJCOmpjoT_pBNvQsV7pzzDVdLYaY
Table 1. HLA-Matched Platelets as a Percentage of All Platelet Transfusions, According to the Initiation of Other Protocols.*
Protocol and Timing of Initiation No. of Years HLA-Matched Platelets Difference from Previous Period (95% CI)     median % (IQR) percentage points No leukoreduction and no ABO matching (1985–1990) 6 12.5 (4.2–13.7) NA Leukoreduction and ABO matching for patients with leukemia and MDS (1991–1999)† 5 2.9 (2.0–3.6) 9.6 (9.4–9.8) Universal leukoreduction (2001–2004) 4 1.4 (1.1–2.0) 1.5 (1.4–1.6) Universal ABO matching (2005–2015) 11 0.4 (0.2–0.8) 1.0 (1.0–1.1) Pathogen reduction of platelets (2016–2019)‡ 4 1.7 (0.8–1.8) ND  
The practical fact is that this can only be implemented by medical technologists, not physicians, and this is a daunting prospect.  But the reality is that ABO mismatched platelet transfusions probably exacerbate rather than prevent bleeding, so waiting for ABO identical is likely better than just transfusing whatever is available.  This is going to require a major change of approach because the (incorrect) dogma, based upon no data, is that ABO doesn't matter for platelets.
I understand why many people's instant reaction is this is not feasible. But it is once technical experts in your transfusion service figure out how to implement it gradually. In our randomized trial back in 1993 (see ref below), the ABO identical group only required <50% the number of platelet transfusions (every other day instead of every day on average) compared with the usual first in, first out regardless of ABO type group. ABO mismatched transfusions create a hostile environment with gigantic immune complexes that compromise subsequent transfusion that may be ABO identical. Avoiding this is key.
Our suggestion is to start gradually. Pick new previously untransfused patients with aplastic anemia and good prognosis AML (young, favorable or normal cytogenetics), groups O or A, and start with them. Eminently doable since your platelet supply is 45% O and 40% A, just like your patients, on average. Get the hang of doing this and prioritizing ABO for at least some patients. Once you get this in place, extending it to other patients and eventually all patients can happen. We use washed O or A platelets and red cells for group B and AB recipients when we don't have group B or AB platelets. No increase in bleeding and fewer transfusion reactions, lung injury and congestive heart failure (what we call TRALI and TACO).
In the end, you have more surviving patients and fewer headaches and transfuse many fewer platelets per patient and essentially no HLA if you can get your referring hospitals to stop our current standard harmful practices. Godspeed. Heal JM, Rowe JM, McMican A, Masel D, Finke C, Blumberg N. The role of ABO matching in platelet transfusion. Eur J Haematol. 1993 Feb;50(2):110-7. doi: 10.1111/j.1600-0609.1993.tb00150.x. PMID: 8440356.
 
Happy to have discussions or visitors so our technical experts can show you how it is feasible.

We stop the transfusion and initiate the transfusion reaction procedure. And until the workup is complete (minus any micro), the patient is unable to receive any other products. Normally it is just something with the donor plasma and Benadryl should cover and propholactically thereafter prior to transfusion. Normally the physicians order Tylenol before the transfusions, so adding Benadryl is not an issue.