Mabel Adams

Not yet available. Being developed by Grifols.  Probably months to a year away from FDA approval.  You can contact them about becoming a testing site for licensure I'd guess.  Until it's licensed you won't be able to use it in patient care, just research/validation.

Some of the worst hemolysis I have seen was in clostridium septicemia.  Both cases were fatal.
 

If you issue blood via a pneumatic tube system, this introduces some additional processes.

The FDA Guidance on Computer Crossmatching calls out that patients with an ABO typing discrepancy should not be allowed to qualify for computer crossmatches. 
" If ABO typing discrepancies exist, you should not rely on a computer crossmatch. This is particularly important if there is mixed field red cell reactivity, missing serum reactivity, or apparent change in blood type following hematopoietic stem cell transplantation. Under those circumstances, your procedures should provide for compatibility testing using serologic crossmatch techniques." 
I wrote our policy to include any non-straightforward ABO types for any reason will be required to get an IS or IAT crossmatch. 

We sometimes find them negative in PEG.  If that or a DTT treated screen is negative, we give units as electronic crossmatched (K matched if DTT used).  Anti-CD38 is not a clinically significant antibody, and we have a negative DTT screen we can turn out which makes the computer happy. 

This may be a little outdated, it's from a prior facility.  We did a tremendous amount of transplant infusion, and this evolved over the decades I was there.
Management of Hematopoietic Progenitor Cell Transplant Recipients.docx

In the UK, the Guidelines would (quite correctly in my own opinion) NOT allow us to perform electronic issue on any sample, whatever the pathology, on a patient where the forward ABO type does not match the reverse ABO type (apart from Newborn babies).

Off the top of my head, as it were, the nearest source I can site is Hult AK, Dykes JH, Storry JR, Olsson ML.  A and B antigen levels acquired by group O donor-derived erythrocytes following ABO-non-identical transfusion or minor ABO-incompatible haematopoietic stem cell transplantation.  Transfusion Medicine 2017; 27: 181-191.  DOI: 10.1111/tme.12411.

We have educated our multiple myeloma specialists to send a type and screen before administering the first dose of a daratumumab (Darzalex).  Our standard operating procedure is to have a panel of three cord blood cells (we have a large OB service) that is a laboratory developed test of sorts.  Cord cells do not express CD38 at interfering levels.
As it turns out we have made more of an issue of this than it warrants.  Patients who have negative antibody screens essentially never develop new antibodies to red cells after being started on daratumumab probably because it potential inhibits B cells function.  Minimal B cell function apparently yields little ability to make antibodies to red cell antigens, which are relatively weak alloantigens, especially when there is no adjuvant or inflammation in the recipient.  That said, a manufacturer is making a soluble CD38  analog that will inhibit the anti-CD38 activity and make testing easier from what I've read.  DTT treatment is also reasonable.  But the good news is that patients on this drug do not make new antibodies. There are literature references to this, and we have probably tested about 500 patients with no new alloantibodies. Mostly non-transfused patients, obviously.

when we see up the side reactions in gel (we call them train tracks) it usually ends up being a cold auto sort of antibody.
we would run a DAT - Poly, IgG and Complement.......
run a cold screen (IS, RT, 4C)
most times the explanation is there in this kind of testing...........
other reason could be rouleaux - 
either way we would switch to PEG here..........and notate in the patient's record to perform future testing in PEG.

reactivity "all over the place" describes my experience of anti-P1.  I have seen negative reactions from cells labelled as strong and cells labelled as weak have been positive. P1 substance (if you have it) to neutralize the anti-P1 provides an elegant resolution.   

I expected to see a stronger reaction with the P1 cells labeled as "strong", but it does react with only the P1+ cells.   Maybe P1 persists better on donor cells than reagent cells.

This is from Human Blood Groups, Deoff Daniels, the second edition.

Mabel, maybe there was an anti-P1 which was initially a  cold reactive one that warmed off by 30 min prewarm technique. But I can't explain why it didn't react with reagent cells after transfudion except there were antigen loss.

The H explanation seems plausible although we didn't see much difference between A and O donors in terms of reaction strengths.  I attached the original panel using Ortho 0.8% pre-diluted cells.  Maybe these keep their H antigen better than the 3% cells we converted to 0.8%.  The panel shown was only a few days from expiring.  The 3% cells expire May 9th. This seems backwards from what we would expect if the antigens were weakening in storage.  However, they are from different manufacturers and in different diluents.  The 3% cells were from Immucor.
 

Thanks Mabel for your explanation. I think we can exclude the protein factor.
1.In my work, I have noticed that the reagent cells express less H antigen than the donor cells do. Our screen and panel cells have 3-month shelf life, but our donor cells only have about 35 days. Even though we do our best to preserve the antigens on panel cells, there are still some losses. Of course, there are other antigen loss other than H.
2.I have read lewis antibodies may react with A type, sorry I can't recall it exactly, I will check it out after this work shift when I get home. If there is an anti-A Lewis antobody, it will react stronger with donor cells. As to the incompatible O donors, my bold guess is they express more Lewis antigen than reagent cells.
Sorry again for my imagination.

That's a good question.  The new sample was tested against Ortho 0.8% screen cells which were both positive due to her anti-D/C/G. Four C & D neg 3% panel cells were converted to 0.8% and run in gel with a 30-minute incubation. They were all negative.  Then the new specimen was also used to crossmatch about 10 units, and we found 3 were compatible.  I checked to see if she was getting TPN but don't see any.  Sometimes that fats and proteins in the nutrition IV cause strange reactions.  Usually, I have seen a positive DAT with it.   If you can further describe the sort of protein you are thinking of, I would appreciate it. 

We have a 42 y.o. Caucasian female with chronic anemia and cellulitis/sepsis needing debridement who has anti-D (2+) & anti-C (3+) by Ortho MTS gel.  She was transfused elsewhere in 2021 and here in 2022, all Rh neg units. Two units each time. Screens were negative then. She has a history that suggests she may have shared IV drug needles at some point. I don't think there is a pregnancy history but not ruled out. She is A neg. Her initial testing in Ortho gel was clearly anti-D with C (could include G) but she had some 1+ reactivity with 4 of 5 D and C negative panel cells. The cell that didn't react was E+, D-, C-. Fya+, Fyb-, heterozygous for Kidd and MNS, but Lea- & Leb-.  Auto control is negative. Three percent panel cells were then selected, diluted with Ortho diluent 2 to a 0.8% suspension and run in gel with a 30-minute incubation. By this method, we detected the anti-D and C antibodies in 2 cells that were D+, C- and 2 that were D-, C+ respectively. We were able to rule out all other typical specificities on 7 non-reactive cells and did not detect the weak reactivity previously found, suggesting that it was antibody to the pre-diluted 0.8% cells' diluent. One A neg, C neg unit was crossmatch compatible by gel that day and was transfused.  Only that unit was crossmatched that day. Two days later (today), they requested more blood. All antiglobulin crossmatches in gel were incompatible--some units were A neg, some O neg.  The reactions in gel were all 2+ or weaker with an atypical appearance of having one to two "stripes" from bottom to top, something we usually associate with cold reactive antibodies. Their strength appeared variable from weakly positive to 2+.  We tried washing the donor cells, prewarming cells/plasma before combining them, 30 min. incubation in gel, and performing PEG XM's in tube which did not help.  PEG was a bit weaker on the 2 units tested by that method (one the strongest reaction in gel and one the weakest), but still positive.  We redrew the patient and got the same results with the new specimen. We did not test reagent cells by PEG. We ended up crossmatching about 20 A neg and O neg RBC units by gel and there were 3 that were truly compatible (not including the one from the first day). She got her second unit of this visit in the past few hours with no problems.  What might cause reactions with AS-1 donor units but not with reagent red cells?  Both are made up in the same diluent and tested by the same process. Some of the donor units were O cells like the reagent cells. Is there anything we should be considering?  I expect she will be back for more blood in coming days to years (with our luck, probably with new alloantibodies since she is a responder who was transfused again).  Thanks for your wisdom.

Same! We were AABB accredited long ago, so still follow the standards, just not quite to such a rigorous degree. We are now TJC and FDA inspected. To my knowledge, FDA doesn't require an associated procedure the way AABB does. As long as there is document control for everything, I think you're covered. I've been in my job 10 years with this inspection setup and not had any issues with my procedures or policies with FDA.  

I was thinking of antigens such as M, N, S, s, Fya, Fyb, Jka and Jkb.  However, they would only tell you if the patient is likely to be a chimera.

As far as what to give the patient, you are right in saying that these results would not help too much, if at all.

From what you have described, group A, D Positive cross-match compatible units should be fine.

Confirmed no BM transplant, no history of leukemia, no recent transfusions, and not born a twin. She is Native American.  We are calling her A pos and assuming she is a weak subgroup or chimera.

Our repeat testing was on the CBC tube.  I once had a phlebotomist reuse a tube that had a flash of someone else's blood in it so wanted to make sure more than one tube on the patient reacted the same.

A3 cells are characterized by mixed field reactions with anti-A and anti-A,B. I don't know what they do with anti-A1 lectin and it may vary depending upon which manufacturer's product you use. As Yanxia pointed out....crude Dolichos extract is NOT specific. Manufacturers formulate (dilute) it to differentiate between A1 and A2 expressions of antigen.

Dolichos biflorus (Horse gram) is amongst the best known lectin in the serologist’s tool kit, but beware!.

The lectin also agglutinates A, B, AB and O red cells that are Cad+ or Tn+.
In addition, as Yanxia so correctly says, it will react with some red cells that are A2 (or, indeed, other subgroups of A) unless the reagent is suitably diluted.

By he description of the agglutinates, I would also favour a possible chimera, as my own experience of A3 is that the agglutinates are usually quite small.  However, as you yourself say, it could be the result of a stem cell transplant of some kind.  I did my project for Fellowship of the Institute of Biomedical Science on blood groups of bone marrow transplant recipients when I was at Westminster Hospital (way back in the last century - well in the 1970's anyway) and found that group A recipients of group O bone marrow transplants, if they were Secretors, sometimes retained a sort of chimera that reacted with both anti-A and anti-A,B as a result of adsorbing soluble A substance onto the group O red cells (with no other apparent mixed-field reactions with other specificities), but did not appear to produce an anti-A post-transplant, or, if they did, it seemed to be adsorbed onto the (apparent) group O red cells coated in soluble group A substance, and had a weakly positive DAT.  Having said all that though, the female patients were usually sterile, and required either donated ova, or had their own eggs frozen prior to the transplant treatment.