Hemolytic Transfusion reaction, but why?

[ElinF]

So we had an oncology patient come in through our ER from out of town. He had MDS and had had several transfusions before. The tech typed him as O Pos. Unfortunately the tech who did this had trouble with the back type. (Front typing as an O, back typing as an A) So she cooled the back type and retested. She did not do an auto control and the patient happened to have a strong cold, making her back type look like an O. She was happy, had matching front and back types, and went on her way. Patient subsequently received O Postive Red cells and O positive platelets. After receiving the platelets, temp spiked and the patient was indeed hemolysing. Bilirubin only got up to 2.5 or something, but he did not have that prior. Still not good.

So I get back from maternity leave and here about this case and start looking into it. Of course it has been a while so we have no specimen left... I am looking at all the retesting done on the patient from the transfusion reaction and i keep seeing this pre-incubated results for his type. He ends up being a weak sub group of A. Meanwhile, we received records from another facility that tells us all this, and indeed he is a weak sub group of A.

So my question is what caused the HTR? O pos blood would have been fine and if he got O platelets, the little bit of anti-A in those would have been most likely A1 anyways, so i can't figure this out. Plus usually you can give any type of platelets. He did not have any antibodies, at least none that we could detect (ab screen was done 2 times, once prior to the trxn and once again afterwards as a check). It was also weird on the TRXN work up the tech that worked it up did a DAT and it was negative (pre and post). Is that possible? So, I am just not sure what went on here. He is from out of town, so we might never see him again, but I guess I want to be prepared if we ever do. Could a cold ab cause this?

Do immunosuppressed patients tend to react more?

Any thoughts?

[Rh-fan]

My first gues is that there were other antibodies present in the plasma of the platelets unit, but than the DAT would have positive.

[Malcolm Needs ☆]

I don't suppose, by any chance, that the platelet pack had a low grade bacterial contamination? I say low grade, because if it were a massive bacterial contamination, the patient could well have collapsed altogether, but, if there was a low grade contamination, it could have caused haemolysis and a spike in temperature. Platelet packs, because of their storage temperature, are implicated in more such reactions than any other blood component.

Was the pack sent to microbiology?

[ElinF]

It was not sent to Micro. I don't think that was even considered at the time (of course this happened in the middle of the night) It was a pheresis unit and our distributor does all the testing for that, so I am assuming the bacterial tests were fine, however, that could be. I was not involved, however we have another blood bank tech who is very seasoned and I think she was originally thinking that (however i don't know where she got this) but that the patient had had a bone marrow transplant. She was thinking that he was A before and now was O? And that maybe the anti-A in the platelets were what was causing it. It was kind of left at that until I was looking at the records faxed to us and the trxn results that we was indeed a weak sub group of A, so that theory went out the door. The pathologist said it was due to the cold in his report, but I don't know if I buy that.

[ColleenA]

I just wondered if you did nay typing on the patient with anti-A,B? Does your blood center perform titers of anti-A,B on their PLT donors? Could there have been a high titer anti-A,B in the PLT donor that recognized the A antigen on the patients weakly positive cells? It seems I only have questions and no answers.

[ElinF]

I just wondered if you did nay typing on the patient with anti-A,B? Does your blood center perform titers of anti-A,B on their PLT donors? Could there have been a high titer anti-A,B in the PLT donor that recognized the A antigen on the patients weakly positive cells? It seems I only have questions and no answers.

I am not sure if they type for anti-A,B on platelet donors. My thinking was though if he was a weak sub group of A he wouldn't react with that anyways, unless by some freak coincidence the donor was had anti-whatever sub group of A the patient had... ??

[Malcolm Needs ☆]

Is the patient really a weak group A, or was he a "full" A prior to his BMT, and also a Secretor.

I don't suppose you know his Lewis type, and I know he has gone back to his "home" hospital now.

If he is a secretor, Type 1 chains will still be produced that are the basis of A substance, and this will adsorb onto the red cells, making them react like a weak A. In addition, this would explain why he lacks conventional anti-A, as the transplanted BM will be, probably, immune tolerant to the A antigen for a long time (sometimes always). There is another theory that the anti-A is inhibited by the A substance, but I don't really subscribe to this one, as the A substance would also be inhibited by the anti-A, and so no A substance would adsorb on to the red cell surface.

Even so, and even if the anti-A,B in the platelets was very high, unless your patient is small in stature, I doubt whether it would have caused this reaction.

However, I also do not "buy" the cold antibody theory either. This would only happen if the unit were ut straight up from the fridge, so that the red cells went in very cold, and the reaction would be immediate and acute. From what you say, the reaction only happened when the platelets were being transfused.

Edited September 23, 2011 by Malcolm Needs
Fingers like thumbs - bad typing.

[ElinF]

The whole time I was looking at this I was assuming he had a transplant as well, but in looking at the records that were faxed to us there was no mention of a bone marrow transplant. I think that was just a wrong assumption on our end, since the back type wasn't matching and we knew he had MDS.

Historical records just stated weak sub-group of A (which were ultimately scanned into our system 1 month after he was here- thank you ER for passing that info along...). I haven't even changed his type from o pos in our system because I couldn't confirm this myself. I did comment though that his type would have to be changed if he came back in the future. And no I do not know his Lewis type...only that he did not have anti-Lea or Leb..

Thanks for your comments!

[Kip Kuttner]

Here is how I look at HTRs.

My first thought would be a high titer anti-A in one (or both) of the platelet products, true there should have been a positive DAT. Could there have been an antibody to a minor blood group antigen in the platelet? True, there should have been a positive DAT.

I doubt the cold would be responsible especially if it did not react at 30 degrees. Cold agglutinin syndrome can occur with cold reacting antibodies because the blood in the capillaries of the skin and extremities is at a lower temperature so the thermal amplitude of the antibody would be good to know. In addition, Garratty's book on immune hemolytic anemias says that fever, chills and acute renal insufficiency do NOT occur with cold agglutinin syndrome. Also, Cold agglutinin syndrome is a chronic condition rather than being acute, so I would think the donor should have a history. The patient history does not fit that of Paroxysmal Cold Hemoglobinuria.

Bacterial contamination can be missed even with the QC culturing we do and it would have been helpful if the patient and unit had been cultured. Additional possibilities include improper handling of the RBC units prior to transfusion (ie storage temp) administration with incompatible IV solutions, administration under pressure or through an IV needle with too small a bore, malfunctioning blood warmer, and the incorrect unit going to the patient, to name a few. Sometimes these reactions are difficult to sort out.

My .02

[JOANBALONE]

I think it is the platelet. Ask the blood supplier to titer the isoagglutinins.

[galvania]

I would be wary of calling a patient with MDS a 'weak subtype of A'. MDS patients can 'lose' their blood group antigens; they often give mixed field results when this happens, but unless you're using gel, it's easy to mistake the mixed field for a weak reaction

[BrianD]

with the DAT never showing a positive reaction and the pre- and post- ab screens being negative (especially the post) i'd lean more towards a nonimmunologic cause.......such as a mechanical problem. some bloodwarmers can produce quite a tremendous forward shear if the delivery line is using a needle with bore less than 19 guage. bacterial contamination could cause a problem like this but the patient would likely show signs of shock very quickly (low bp, high heart rate).

[Mabel Adams]

I have seen small bili spikes like this in patients that got older stored blood. They have to process the dead RBCs in the unit. There are many reasons why a patient would spike a temp only some of them related to the transfusion. What other signs of hemolysis did you find besides the bili? Specimen visually hemolysed? Decreased haptoglobin? Increased LDH?

[Auntie-D]

I'd go with the old blood side - the bili rise wasn't huge so could be due to lysed donor units. What was the patient's pre and post potassium?

Another thing - was the patient given irradiated blood? There is an outside chance of GVHD...

[Malcolm Needs ☆]

TA-GvHD is associated with T cells, rather than B cells, and so I cannot see that it would cause haemolysis - but it would cause death!!!!!!!!!!!!

[Auntie-D]

True, true

Edited September 29, 2011 by Auntie-D

[sshel55]

Elin,

I would report this to your blood supplier and ask them to see if this particular donor had ever been implicated in a hemolytic reaction previously and to perform an isotiter at both room temperature and AHG phases. High titer isoagglutinins can indeed cause brisk hemolysis and if the titers are high enough (some are well over 1000), they would react with A subgroups. There are numerous case reports and articles that demonstrate hemolysis caused by ABO incompatible platelet transfusions. Given the fact that the patient experienced fever and hemolysis during the platelet infusion, it is prudent to look at the platelet. If the high titer isoagglutinin was in fact primarily IgM, it could cause intravascular hemolysis and might not be detected by the DAT.

[Dr. Pepper]

A few thoughts:

You seem to include an autologous negative control (which your tech didn't do) for your cold backtype - you might consider an antibody screen instead so that alloantibodies can be detected as well as autoantibodies. It could have been anti-P1, etc. causing the spurious rxn with the A1 cells as easily as an autoantibody. You also might consider including in your workup protocol to always do a culture on any component if the rxn symptoms include any associated with bacterial contamination: fever, chills shock,hemoglobinuria, DIC, renal failure, abdominal cramps, diarrhea, vomiting, muscle pain.

If using tubes, was the DAT done with polyspecific AHG and read microscopically? I like the idea above that the culprit was IgM in the platelets, hence the negative DAT, but I would also think that there'd be some complement still bound and detectable as well as IgG since most group Os have some, assuming there were affected cells still surviving.

Looking at the red cells transfused, there have been cases reported of "undetectable" antibodies causing hemolysis, which in the end turn out to be detectable by other methods such as Polybrene. Was a full crossmatch performed to rule out abs to low incidence ags? One can also use serum rather than plasma so that complement binding abs can be detected. Rarely, some abs like Kidds may be more detectable by the complement they bind than by IgG.