Just looking for opinions: I have an oncology pt who has been receiving A= red cells (2-4u/week) for the past 7 months, with an occasional platelet thrown in. Diagnosis is MDS. the plts recently have been group O and few O= rbcs also, due to rapid unavailability of A=, cmv= irradiated products. I did a DAT on this guy - 2+ in gel eluting anti-A. My Medical Director and I felt this was secondary to the group O products. This was at the beginning of November. 2 days ago he displays an anti-A1, reactive at 37C, so we are going to give him group O cells from now on. My thought now is that his DAT is his anti-A1 reacting with transfused A1 cells. My question is - could his disease have modulated his A antigen to such an extent that he developed the antibody? I had not typed his A ag and it seems odd that he would suddenly develop this after months of transfusions. Any and all opinions will be gratefully accepted.

Is the eluate only reactive with A1 cells or also A2 cells?

I would also like to know the answer posed by Anna, but, yes, myeloid-type problems have frequently been associated with weakening of ABH antigens, and so it is quite possible for your patient's condition to be associated with an anti-A1 that has become clinically significant.

Scratching a very, very old head, I recall that, when I was working at the now defunct Westminster Hospital, we had a group A haemophilia patient who also suddenly developed a clinically significant anti-A1 (although, in his case, there was no apparent reason for this), so, if it can happen, at some point, it is going to happen, and, in this case David, you appear to have drawn the short straw!

I did not check the eluate vs A2 cells, though I may try again as I have a current specimen still with an IgG+DAT. At the time (November) it was only serendipitous (actually an after thought when the elution wss non-reactive) that I ran it vs A cells at all. Only 2 days ago did ab show up in the reverse grouping. I'll update when I run that.

The patient may also be either a low responder or somewhat immune compromised due to his disease/treatment. This might explain the time lag in developing the antibody.

Also, I don't see any mention of having tested the patient cells with A1 lectin any time in the past. It would be difficult to test them now with the transfusion history. Malcolm, any suggestions how to do this?

I think at this point I would probably assume the patient is an A2 and it just took him awhile to respond to the A1 cells and the DAT is showing against all the A1 donor cells you've given him.

No real thoughts John, apart from very, very expensive molecular work - not worthwile I would suggest, as it is easy to give group O red cells.

John I did not type is A ag at the onset of transfusions . . . I did perform it last week where he was negative with A1 lectin.

David, I would have been very surprised if you had A1 typed him prior to the first transfusions. I know I never would have without a good reason. Looks like he is, as expected, an A2, just slow on the antibody production. Even with the D antigen some people make the antibody with a dose as little as 100 microliters while others can be transfused all day with D+ rbcs and never make the anitbody. That's what makes the world so interesting and frustrating.

OK - so I ran the eluate vs A1 and A2 cells: A1: 4+; A2: 2+. Screening cells are negative. Last wash was negative. Anti-A? Seems like that to me . . . Could this guy have an auto-anti-A? or is the sensitivity in gel such that the A2 cells are reacting with an anti-A1 (I don't think so)? If I ran it in tubes, the A2 cells might be negative . . . Opinions . . .

Thanks

Wow, this just gets stranger and stranger. You've past my expertise. Malcolm, you're up!

Did you run the eluate with MTS? MTS is changing a lot of the 'old rules' we grew up with and I do remember something about 'A1 not being a pure antigen' ... hmmm, ok here it is in Peter Issitt's book: " ... the difference between A1 and A2 is primarily quantitative, meaning that A1 and A2 cells carry different amounts of the same antigen." So, yes, you can 'type' A2 cells as A1 positive if you use a very sensitive method, e.g. MTS.

I agree with the others:

You have a patient who is now making Anti-A1 and it has attached to the donor cells.

Ah, life was so much simpler when we had very simple tools to play with!

My thoughts: Given that all this discussion is 'merely academic' (Hey, this IS how we have fun, right?) ...

a) report the antibody as Anti-A1 (if it reacts at 37C, it is 'clinically signficant') for now

give him O cells for the next few months to eliminate the confusion

c) if this patient continues to have a positive IgG-DAT due to Anti-A1 after all those A1 cells are out of his system, then I'd change it to an auto-antibody and transfuse accordingly.

Keep us posted about how this goes in the future, ok?

Auto-anti-A is disappearingly rare, but that does not mean that you have not "got one on your hands". We had one last year, and I just didn't believe it until I had it checked by the IBGRL.

It could also be that you are getting some reactions with your A2 cells, as well as your A1 cells because, although your A2 cells are "marked" as A2 cells, it does not mean that they are "actually" A2 cells. The difference between A1,Aint, A2, ABantu, A3, Ax, Am, etc red cells, in terms of antigenicity is, to a certain extent, a grey area, and it may well be that it is a continum in terms of the number of antigen sites per red cell (the lower range of the number of A antigen sites for an A1 per red cell overlaps with the higher range of the number of A antigen sites for an A2 per red cell).

If you like, it is the antigen equivalent of the sort of reactions you get when an individual eventually makes an anti-HrB. They start off looking like they've made an anti-e, then look like they've made an anti-e+C or anti-e+Ce, then have "definately" made an anti-hrB and eventually wind up making an anti-HrB (putting you right in the muck).

"Strange" antigenicity is a feature of a lot of "carbohydraty" type antigens (of which ABO is an example). Just think of the different strengths of the P1 antigen that you get or, come to that, the Lewis antigen. Female baby starts off as Le(a-b-), then becomes Le(a=b-), then, briefly, becomes Le(a+b+), and eventually becomes Le(a-b+). Then, in later life, she becomes pregnant, and goes from being Le(a-b+) to, briefly, Le(a+b+), then Le(a+b-) and then, in some cases, Le(a-b-) again, and may even start to produce Lewis antibodies! I know that this is to do with the soluble Lewis antigens being mopped up by the "over-production" of certain plasma lipids during pregnancy, rather than Lewis antigens not being produced during pregnancy, but I think you can see what I mean.

Anyway, it all boils down to the fact that you have to treat the apparent anti-A1, certainly in this case, as a true clinically significant anti-A1.

I wonder whether the MDS has not so significantly altered this guy's A antigen that his own anti-A is not recognising it as something foreign, so a sort of anti-Altered-A. In which case, this should be transient and disappear as his MDS improves with treatment

Excellent point, well made Anna.

I wonder whether the MDS has not so significantly altered this guy's A antigen that his own anti-A is not recognising it as something foreign, so a sort of anti-Altered-A. In which case, this should be transient and disappear as his MDS improves with treatment

That is my original line of thought . . . altered A ag due to his disease. Actually, he is scheduled for BMT in January. Do you think that the transplant people should be aware of his current serology?

Also - I did run the eluate in tubes: A1: 2+, A2: w+

Yes, let them know. If they end up changing his blood type with the transplant, things can get a little confusing anyway, and it would be helpful to them to know of any past issues.

It could also become an issue if they end up giving him an A BMT. I would think??

It could be a case of minor incompatibility caused by the O platelets transfused with a powerful anti A

Just a follow up: my pt is on his way for BMT. His serum anti-A1 only was apparent in one specimen . . . never recurred on subsequent T&Ss. His DAT is now negative (must have finally gotten rid of all the A1 cells). His ABO typing is mixed field, as would be expected. The Transplant folks are aware of his serologies.

Thanks to everyone for thier input.

Just a follow up: my pt is on his way for BMT. His serum anti-A1 only was apparent in one specimen . . . never recurred on subsequent T&Ss. His DAT is now negative (must have finally gotten rid of all the A1 cells). His ABO typing is mixed field, as would be expected. The Transplant folks are aware of his serologies.

Thanks to everyone for thier input.

Minor Incompatibility

Thanks for the update..Its nice to see how things turn out :cool:

I had a patient with a similar thing going on. Diagnosis was aplastic anemia. And the 1st specimen showed warm auto. After a while the warm auto and screen became neg. The way I caught the anti-A is when I did crossmatches at IgG in gel not at IS. IS was neg. Then I proceeded to think we just missed anti-A1 in back type when we typed 1st specimen and that maybe chemo decreased the IgM anti-A1 reactivity at IS in the current specimen. So I crossmatched 4 different A1 neg units in IgG gel all neg. And I crossmatched 4 different A1pos units all positive 2+. All 8 crossmatches were performed in same run. Never could antigen type patient for A1 because if transfusion history. I assumed she was Asub with an anti-A1, but I guess it could have been an auto anti-A1. And maybe the cause of patient's disease. We gave O pos units and ended up changing type completely to O. Patient went to a different hospital for a stem cell transplant. Not sure how it turned out.

I had a patient with a similar thing going on. Diagnosis was aplastic anemia. And the 1st specimen showed warm auto. After a while the warm auto and screen became neg. The way I caught the anti-A is when I did crossmatches at IgG in gel not at IS. IS was neg. Then I proceeded to think we just missed anti-A1 in back type when we typed 1st specimen and that maybe chemo decreased the IgM anti-A1 reactivity at IS in the current specimen. So I crossmatched 4 different A1 neg units in IgG gel all neg. And I crossmatched 4 different A1pos units all positive 2+. All 8 crossmatches were performed in same run. Never could antigen type patient for A1 because if transfusion history. I assumed she was Asub with an anti-A1, but I guess it could have been an auto anti-A1. And maybe the cause of patient's disease. We gave O pos units and ended up changing type completely to O. Patient went to a different hospital for a stem cell transplant. Not sure how it turned out.

What was the original diagnosis Jyoung, wich required a transplant?

I don't know. I'm sorry. The patient was referred from another hospital. This patient came with a Warm Auto.

I don't know. I'm sorry. The patient was referred from another hospital. This patient came with a Warm Auto.

Thanks for that Jyoung. I'm sorry, I missed the bit about the diagnosis of aplastic anaemia, but what was passing through my mind was the possibility that the transplant may have been required for some sort of "myeloidy" type thing, like AML, and the aplastic anaemia would not rule this out, and this could well explain the weakened ABO antigens on your patient's red cells, much more so than the chemotherapy.