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2 Mysteries


Brenda K Hutson

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So we have had 2 patient mysteries in the past week.  One of them probably has a simple solution....but is just not something I have ever seen in over 30 years.  The other one is more of a mystery.

1st case:  We received a Cord Specimen on the baby from an A NEG mom to evaluate for Rhogam.  The baby typed 4+ with Anti-A, but 1+ with Anti-B.  We did wash the cells many times.  We also obtained a heelstick but obtained the same results.  I am used to seeing weak A typing on newborns; but not used to seeing it with Anti-B (but then statistically, I have seen many more A's over the years than B's); especially when it was so strong with the Anti-A.  Have any of you seen that weak of typing with Anti-B on newborns, or are there any other thoughts on what is occurring here?

 

2nd case:  62 year old male with diagnosis of COPD, Dyspnea, GI Bleed, Chemo (as recently as yesterday).  So ongoing problems.  He has had MANY transfusions of RBCs and Platelets over the past year; including past 3 months.  The patient is A POS.  Yesterday, he was transfused with an O POS Platelet (we only keep 2-3 in-house at any given time so just have to give what we have, and do so by outdate).  Anyway, after receiving only 151 cc's of Platelets, he had Chest Pain, Respiratory Distress and Vomiting.  He was transferred by ambulance the 1 block to the Hospital ER.  All of our clerical check was fine.  Our Policy for giving Platelets is that we just have to have a historical type on the patient; it does not have to be a current type.  However, the Cancer Center had drawn a HOLD specimen that morning so as it turned out, we did have a pre-transfusion specimen (just had not been tested yet).  Upon testing both the pre- and post- specimens, the only issue we came across was that the pre-transfusion IgG DAT was Negative, but the post-transfusion IgG DAT was 3+.  When we spoke to the Medical Director of our Donor Facility, he said to report it as a hemolytic transfusion reaction.  Problems with that are:  After whatever treatment they gave patient in ER, he was sitting up and feeling just fine.  Also, no indications of it being TRALI.  So we became concerned that perhaps we had a platelet with a high-titer Anti-A,B.  We performed an Eluate on the post specimen and tested it against screening cells plus A1 and B cells.  All testing was NEG.  Now we were really stumped.  We had the patient re-drawn and now, several hours later, the IgG DAT had dropped to 1+.  Not a dramatic drop in Hgb.....from 7.4 before transfusion, to 7.1 after transfusion, to 6.9 this morning.  So my last "guess" was that perhaps he was just really unlucky and the donor of the platelets had an Antibody to a Low Incidence Antigen, and the patient just happened to be Positive for that Low Antigen??  So we are testing just the Lows that are on our panels (Cw, Kpa, Jsa and Lua).  Of course there are a lot more Low Incidence Antigens that it "could" be if that is what caused this.  But that decrease in strength of the DAT, in light of not really seeing evidence of hemolysis, is very confusing.  And if it is an Antibody to a Low Incidence, due to his many transfusions of RBCs, is the Antibody attaching to his own cells, or to donor cells he previously received which may have been Positive for a Low Incidence Antigen?  Any thoughts/ suggestions.

Also, as I am completing this, my Tech. just brought me a gel card with the results from 2 of the Low Incidence Antigens.  It looks like the card spun at an angle so I want it repeated, but it appears that the eluate is reacting with the Lua+ panel cell.  But I wouldn't expect an Anti-Lua to cause a severe reaction in a patient like that.

Anyway, will keep you posted on our serological results.....but if you have any other ideas/ thoughts, would love to hear them.

Thanks in advance for your input,

Brenda Hutson, MT(ASCP)SBB

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Ok, so this is even more confusing.  The repeat of the Lua+ cell was definitely Positive (tested with eluate), however, we then decided to test the plasma from the platelets against the same cell, and it was non-reactive.  If there was truly an Anti-Lua in that Platelet, I would have expected it to also react against that cell.  Yet there must be some significance in eluting an Anti-Lua; and in a Negative Direct Coombs before transfusion and 3+ Positive after transfusion??  I feel like we are missing something but I don't know what it is.  It is possible that the patient's reaction had to do with chemo drugs he had been given....maybe even possible that the positive DAT was due to some drug interaction.  But how to explain the eluted Anti-Lua??

Thanks again,

Brenda

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it is a long post to me :P

the first one, i often see B antigens are  weaker than A antigens on our newborns, but ont as weak as 1+, i think it maybe an ABsubgroup.

the second one,"Lutheran antibodies have not been implicated in immediate haemolytic transfusion reactions, although they may have been responsible for mild delayed reactions and post-transfusion jaundice."I think the symptom after transfusion fit it.

Geoff  Daniel, Human bloog groups,second edition, 279,230

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I would totally agree with Yanxia about Case 1 probably being an ABsubgroup as being the most likely answer to your first case, but it would be wonderful if you were able to follow up the case at six months, just in case it is a genuine case where the B transferase is so "weak", that it is almost "overwhelmed" by the A transferase.

Another possible explanation, one which is unusual, but not unknown with monoclonal ABO antibodies (and will not be popular with the manufacturer of your ABO reagents!), is that your anti-B is actually an anti-B(A), whereby the anti-B is capable of reacting weakly with group A red cells (the opposite can also happen with anti-A(B) whereby an apparent anti-A can react weakly with group B red cells).

Case two is very intriguing.  I would echo that anti-Lua is not what would generally be considered to be clinically significant.  There certainly appears to be an anti-Lua there, which is sensitising his red cells in vivo, which may well have been introduced by transfusion of another component (given his pathology, I am assuming that he has received more than just this unit of platelets within fairly recent times).  However, it could well be that the plasma from this particular unit of platelets could have contained an antibody directed against a completely different low-prevalence antigen, such as an antigen within the 700 series.  If this is the case, even a relatively large Reference Laboratory may well have grave difficulty in identifying the specificity, as they may not have access to red cells expressing the cognate antigen.  In addition, such antibodies often cross-react with multiple low prevalence antigens, and, on top of that, individuals who make such antibodies often produce multiple antibodies directed against actual low-prevalence antigens (by that, I mean that this is not cross-reactivity).  This would explain the positive DAT.  Some of these antibodies do cause red cell destruction, which would explain the later negative DAT, but not to such an extent that you would see symptoms such as dark urine.

Obviously, I have no idea of the drugs he is taking, but this doesn't sound like a drug-induced reaction to me, as I would certainly expect to see dark urine, and other evidence of haemolysis.

 

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I have also seen neonates with strong reactions to anti-A and weak reactions to anti-B.  I did additional testing to confirm that it was a true anti-B reaction and not something non-specific but never was able to obtain a later sample to see if the strength of the reaction was any different.  

Case 2:  unless I missed something, there is no evidence of hemolysis, correct?  I would hesitate to call a hemolytic reaction without evidence of actual hemolysis.  Was the pre-transfusion sample drawn prior to the chemotherapy?  We have had two cases where the patient was sent over for type and cross after chemo for RC transfusions and pre-transfusion testing showed pan-reactivity.  When we brought the patient back in the next day to draw additional sample for our reference lab the reactivity was gone.  We never performed an eluate since the second sample was negative so I don't know what to thing about the anti-Lua reactivity, other than what Malcolm said about it possibly being from a different product.

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12 minutes ago, BankerGirl said:

 

Case 2:   Was the pre-transfusion sample drawn prior to the chemotherapy?  We have had two cases where the patient was sent over for type and cross after chemo for RC transfusions and pre-transfusion testing showed pan-reactivity.  When we brought the patient back in the next day to draw additional sample for our reference lab the reactivity was gone.  We never performed an eluate since the second sample was negative.

BankerGirl, was your patient on something like ALG or ATG?

Edited by Malcolm Needs
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Just a thought,

Has the donor center been contacted to review the Donor's history?  Meds,(prescrip or herbal), donor not feeling well in the past, or afterwards of the donation?  Could they test the donor's plasma/serum against other antigens of low frequency?  They should have extra or could call the donor in.

Patient may be reacting to something specific with the donor's donation.   Patient has allergies to something the donor is taking (meds or etc).  Could be a cytotoxin from some bacterial exposure the donor has had.   Once we had a case with a snake handler, donor had or has had Salmonella  but felt fine at the time of donation, and the toxins were present in the platelets' plasma..... similar reaction.  (no positive DAT though).

I agree with previous response from Mr. Needs,  that DAT and eluate specificity could be co-incidental, especially since he has been multi-transfused and may not be related to the immediate "transfusion reaction".

Interesting case!  Thanks for sharing....

 

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Thank you all for your input.  With regard to the comment that the post was long....I tend to like to explain things thoroughly so readers have all of the information I have, and know what my thoughts are up to that point.  Sorry, just my style. :P

  • ABsub did also occur to me, but in all honesty, I have only rarely seen this in my 30+ years (just lots of AsubB).  Also not sure if it was just weak due to age so would not want to "label" them as ABsub if 6 months from now, they typed 4+ with Anti-B.   So was a little nervous about coming to that "official" conclusion.  So we did make the recommendation that if they really wanted to know, they could try submitting a new specimen in about 6 months.
  • I agree that there could be a different Low Incidence Antibody that caused the transfusion reaction (we only tested what we could get from our panels).  We are sending pre and post specimen plus leftover platelets to the Red Cross to see what they come up with.  They may or may not elect to run a panel of some Low Incidence Antigens from their frozen inventory; but of course they can't test every Low Incidence Antigen so it would just be a "hit or miss."  But I guess what is still just odd to me is that the DAT was negative before the transfusion (just that morning; was just sent because the patient was being seen by their Oncologist and has been using blood products steadily, so they wanted us to have a specimen available should they need to transfuse more RBCs in next few days); then clearly positive right after the transfusion; and there was definitely an Anti-Lua coating the cells (but also a mystery as to why the strength of the DAT would so obviously weaken in just a few hours, if no evidence of hemolysis).   Also, with regard to the comment from BankerGirl about why we were calling it a hemolytic transfusion reaction.  We had called the Red Cross Medical Director right after we discovered the Positive DAT and he instructed us to do that; however, our Medical Director did not state that on the Transfusion Reaction Report; but in fact, stated that the reaction may not have even been related to the transfusion; could have been coincidental timing (but that still doesn't explain a Negative DAT becoming Positive from Pre to Post).   So is the suggestion then that while we eluted the Lua.....that had we performed an eluate on the negative DAT cells from the morning, we may also have eluted it then but it is just that it is not present on enough cells to have resulted in the Positive DAT (i.e. as an explanation as to why the DAT changed but no Anti-Lua was identified in the platelet plasma)?  I am still trying to make sense of that part; that if it was not the cause of the reaction and was not in the platelets, the assumption would have to be that it was already present and coating the cells prior to the transfusion; just not enough to cause a positive DAT; but enough to come off in a concentrated eluate?   The patient had received numerous red cell transfusions over a long period of time; so there certainly could have been a small population of transfused cells that were Lua POS to which the patient's Anti-Lua attached?  Also, Antibody Screen Negative, so no "free" Anti-Lua (unless low titer).
  • If Red Cross comes up with anything more concrete, I will pass that along; but I really appreciate your input on this mystery!

Brenda Hutson

 

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3 hours ago, Brenda Hutson said:

Thank you all for your input.  With regard to the comment that the post was long....I tend to like to explain things thoroughly so readers have all of the information I have, and know what my thoughts are up to that point.  Sorry, just my style. :P

  • ABsub did also occur to me, but in all honesty, I have only rarely seen this in my 30+ years (just lots of AsubB).  Also not sure if it was just weak due to age so would not want to "label" them as ABsub if 6 months from now, they typed 4+ with Anti-B.   So was a little nervous about coming to that "official" conclusion.  So we did make the recommendation that if they really wanted to know, they could try submitting a new specimen in about 6 months.
  • I agree that there could be a different Low Incidence Antibody that caused the transfusion reaction (we only tested what we could get from our panels).  We are sending pre and post specimen plus leftover platelets to the Red Cross to see what they come up with.  They may or may not elect to run a panel of some Low Incidence Antigens from their frozen inventory; but of course they can't test every Low Incidence Antigen so it would just be a "hit or miss."  But I guess what is still just odd to me is that the DAT was negative before the transfusion (just that morning; was just sent because the patient was being seen by their Oncologist and has been using blood products steadily, so they wanted us to have a specimen available should they need to transfuse more RBCs in next few days); then clearly positive right after the transfusion; and there was definitely an Anti-Lua coating the cells (but also a mystery as to why the strength of the DAT would so obviously weaken in just a few hours, if no evidence of hemolysis).   Also, with regard to the comment from BankerGirl about why we were calling it a hemolytic transfusion reaction.  We had called the Red Cross Medical Director right after we discovered the Positive DAT and he instructed us to do that; however, our Medical Director did not state that on the Transfusion Reaction Report; but in fact, stated that the reaction may not have even been related to the transfusion; could have been coincidental timing (but that still doesn't explain a Negative DAT becoming Positive from Pre to Post).   So is the suggestion then that while we eluted the Lua.....that had we performed an eluate on the negative DAT cells from the morning, we may also have eluted it then but it is just that it is not present on enough cells to have resulted in the Positive DAT (i.e. as an explanation as to why the DAT changed but no Anti-Lua was identified in the platelet plasma)?  I am still trying to make sense of that part; that if it was not the cause of the reaction and was not in the platelets, the assumption would have to be that it was already present and coating the cells prior to the transfusion; just not enough to cause a positive DAT; but enough to come off in a concentrated eluate?   The patient had received numerous red cell transfusions over a long period of time; so there certainly could have been a small population of transfused cells that were Lua POS to which the patient's Anti-Lua attached?  Also, Antibody Screen Negative, so no "free" Anti-Lua (unless low titer).
  • If Red Cross comes up with anything more concrete, I will pass that along; but I really appreciate your input on this mystery!

Brenda Hutson

 

I, for one, appreciate your further thoughts.  I am still thinking myself (but, really, I am as baffled as you about Case 2 (unless the patient was given something like ALG or ATG as part of his therapy).

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I have to admit that I am not familiar with the abbreviations of ALG or ATG (unless that is referring to a type of antihuman globulin)?  We did not ask for the patient's medication list but a comment I just noticed that our Medical Director wrote on paperwork we are sending to Red Cross (we decided to send all of this to them in case they could find something we could not), was that other possible explanations were Dyspnea secondary to COPD or Drug Reaction.  But there is still just that darned confusing DAT (I suppose could have been non-specific drug binding with the "coincidental" Anti-Lua eluted).

Anyway, will definitely update you all if I hear anything different from ARC.

Thanks again for your input; always invaluable. :)

Brenda Hutson

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ALG is anti-lymphocte globulin and ALT anti-thymocyte globulin.  These are heterophile antibodies that are given to patients as treatment (or, rather, part of treatment) and, when first given, often cause a positive DAT, which disappears relatively quickly in vivo, so that blood taken immediately after dosing has a positive DAT, but blood taken a little later has a negative DAT.  There may well now be other such drugs, as I came across this effect a few years ago now.

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On ‎8‎/‎18‎/‎2017 at 1:59 PM, Malcolm Needs said:

ALG is anti-lymphocte globulin and ALT anti-thymocyte globulin.  These are heterophile antibodies that are given to patients as treatment (or, rather, part of treatment) and, when first given, often cause a positive DAT, which disappears relatively quickly in vivo, so that blood taken immediately after dosing has a positive DAT, but blood taken a little later has a negative DAT.  There may well now be other such drugs, as I came across this effect a few years ago now.

Our Medical Director checked his files and he was not on either of those drugs.  The only drug of interest she saw was Promacta, but not sure if that is a drug that acts in this same manner?

Thanks,

Brenda

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58 minutes ago, Brenda Hutson said:

Our Medical Director checked his files and he was not on either of those drugs.  The only drug of interest she saw was Promacta, but not sure if that is a drug that acts in this same manner?

Thanks,

Brenda

Sorry Brenda, but I don't know that either, however, I found the following on a website showing various side-effects of Promacta, and it does list hemolytic anemia as being a common side effect (1 to 10%).  If this is what is happening to your patient, I would suspect that any positive DAT could be dose dependent - BUT i AM ONLY "THINKING OUT LOUD"!

Hematologic

Very common (10% or more): Anemia
Common (1% to 10%): Decreased hemoglobin, decreased neutrophil count, decreased white blood cell count, hemolytic anemia, increased INR, lymphopenia, prolonged activated partial thromboplastin time
Uncommon (0.1% to 1%): Anisocytosis, eosinophilia, increased hemoglobin, increased band neutrophil count, increased platelet cell counts, leukocytosis, myelocytosis, presence of myelocytes, thrombocytopenia[Ref]

Edited by Malcolm Needs
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I guess there is no possibility that there were free red cells in the platelets?

Also, was the patient given anything else at the same time as the platelets?  It may be that there was a transient reaction between two different things both being administered roughly at the same time, and that the complex 'stuck' on to the red cells for a while???

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The patient had just finished chemotherapy.  But if for example, he had also just received that drug, it could just be coincidental timing that the drug reacted with his red cells while he was being transfused platelets?  Still just guessing.  Keep those thoughts and ideas coming and if I hear anything from Red Cross, I will let you all know!  I am learning from this one. :)

Thanks,

Brenda

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On ‎8‎/‎29‎/‎2017 at 2:34 PM, StevenB said:

Just curious...what type of eluate did you perform and if Acid, did you use cold saline and wash solution when prepping the patient's cells?

We use Room Temperature Saline and Cold Wash Solution.

Brenda

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  • 3 weeks later...

Well, not quite sure how it ended up this way in that we spoke to the Medical Director at the ARC twice (he had said to report it as a hemolytic transfusion reaction); I sent them copies of ALL of the work we had performed, as well as a copy of the Transfusion Reaction Form showing the symptoms and work-up; and I attached a letter, summarizing everything that had transpired, and what our additional thoughts were (i.e. Antibody to a different Low Incidence Antibody being just one other thought).

I received an e-mail back from the Medical Director a couple of weeks later, and here is what was written:

I received this report of a potential TRALI reaction from your hospital, and after investigating the sex of the donor involved in this case--a man--I have decided not to investigate the case. The reason for not investigating the case is that the donor in TRALI cases are previously pregnant women with HLA antibodies, and male donors do not have HLA antibodies. You also had a concern for TACO, but TACO is not associated with any donor or blood component characteristics.  I am going to send you  formal follow up letter with this decision.

So I e-mailed him back, reminding him of our conversations (we never mentioned TRALI or TACO as a possibility for many reasons), and mentioned that I had also attached a letter (which may never have reached him; I can't say.....so I attached it again to my Reply e-mail).  I have never heard back from him.....so I guess it is a closed case.

We went as far as we could with a work-up.....so if ARC is dropping it at this point, I guess we are also.  The patient has subsequently been multiply transfused w/o incident, but we may never know what actually caused this 1 reaction for the patient.

Brenda Hutson, MT(ASCP)SBB :unsure:

 

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