Non ABO, Non Antibody Mediated Hemolytic Transfusion Reaction

[LAURIE]

Elderly female, Group O Positive with a negative antibody screen received three single unit (OPOS) leuko-reduced red cell transfusions two weeks apart with no untoward effects.  One week after last single unit transfusion, received two units (OPOS)on an outpatient basis and was discharged.  One week later, received two units (OPOS) and experienced a febrile reaction with hemoglobinuria; she was admitted for a transfusion reaction workup.  Post reaction sample was hemolyzed with a negative antibody screen and negative DAT.  Full crossmatches performed with pre and post samples were compatible.  Eluate was negative.  Sample drawn immediately after(#1) reaction and one 24 hours post(#2) was referred to reference laboratory.  Sample #1 acid eluate demonstrated Anti-D in saline; microscopic to weak positive with all cells in PEG, showing no specificity, unable to determine if anti-D is allo-or autoantibody.  Serum hemolysis resolved in 24 hours.  One week later admitted and transfused with two units ONEG leukoreduced red cells and again experienced a febrile hemolytic episode; DAT pre and post negative-hemolysis resolves in 24 hours.  Two days later receives one unit (ONEG) washed red cells; no reaction or hemolysis. Next day, receives one unit (ONEG) washed red cells and experiences hemoglobinuria and post sample hemolyzed; again DAT negative.  Finally, one week later, receives one unit (ONEG) washed red cells thru the blood warmer with no post hemoglobinuria or serum hemolysis.HELP!

[galvania]

My first reaction is that this lady is not a true D+, and that she has an anti-D.  DAT and eluate negative because all the cells were haemolysed.  Having said that it is very very odd to have a haemolysis like that with an anti-D.  The haemolysis might be unrelated to the transfusion.  What are the clinical details of this patient?

[LAURIE]

Anemia!  Thats all we get

[Malcolm Needs ☆]

I just wonder if the lady has a low titre auto-anti-I, but of wide thermal amplitude.

 

It would be interesting to know several things.

 

Firstly, is she of small stature?

 

Secondly, what was the rational for giving washed cells - did they think that she had anti-IgA?

 

Thirdly, in view of the fact that a transfusion through a blood warmer seemed to be efficacious, were all of the units allowed to come to ambient temperature prior to transfusion, or were all of them (apart from the first unit of washed cells) given straight from a cold environment?

 

Lastly, are all of your samples anti-coagulated in EDTA?  If so, it may just be worthwhile trying a screen with a fresh clotted sample, to see if there is any haemolysis in vitro in the screen and/or the cross-match.

[kirkaw]

Am I correct in following that this lady got 7 units of blood in a 6-week period before the 1st febrile reaction?

Could this hemolysis be drug induced?

[LAURIE]

I just wonder if the lady has a low titre auto-anti-I, but of wide thermal amplitude.

 

It would be interesting to know several things.

 

Firstly, is she of small stature?

 

Secondly, what was the rational for giving washed cells - did they think that she had anti-IgA?

 

Thirdly, in view of the fact that a transfusion through a blood warmer seemed to be efficacious, were all of the units allowed to come to ambient temperature prior to transfusion, or were all of them (apart from the first unit of washed cells) given straight from a cold environment?

 

Lastly, are all of your samples anti-coagulated in EDTA?  If so, it may just be worthwhile trying a screen with a fresh clotted sample, to see if there is any haemolysis in vitro in the screen and/or the cross-match.

*She is not a small stature women: 179 lbs 5"2"

* No particular rationale for giving washed cells

* I would say all units given from a cold environment except when blood warmer used; reference lab ruled out over thermal range of 4-37C

* All samples are EDTA...next visit I shall request both EDTA and clotted sample for evaluation

She seems to tolerate single unit transfusions best, but why? nothing particularly significant with medication history...just want a reason!!

[LAURIE]

Am I correct in following that this lady got 7 units of blood in a 6-week period before the 1st febrile reaction?

Could this hemolysis be drug induced?

  well, we found out after the first hemolytic reaction ( that is after seven units in seven weeks), she had experienced hemoglobinuria at home after she received two units same day (#4 and #5) week 6...so much for outpatient instructions post transfusion.  medication list seems innocuous...something for pain, vertigo, anxiety and nausea

[Malcolm Needs ☆]

????????????????????Hmmmmmmmmmmmmmmmmmmm??????????????????????????  Thinking cap being applied!!!!!!!!!!!!!

[Sko681]

Could it be some sort of bizzar reaction to the anticoagulant in the RBC's?  I know that's unlikely but... Is that even possible???  We had a similar incident with a cancer patient before.  We could find no reason for her transfusion reaction.   I like the idea of using a clotted sample.

[Mabel Adams]

Mechanical damage ruled out?  Transfusion process not suspect in any way?  Infusing with saline only?  Not likely thermal damage to units since it happens repeatedly. IgA, IgE or some other class of antibody? Do any others fix complement so as to cause intravascular destruction? I remember someone telling me once of an anti-E that killed a patient that they couldn't get to come up in any testing except, I think, enzyme. (Now that I think of it I wonder if what they found was an innocuous enzyme-only anti-E that was a red herring.)   What about one of those complement-dependent Kidd antibodies we always worry about but which are pretty rare?  The serum specimen should help but use poly AHG (or anti-complement anyway).  If the blood warmer keeps working, keep using it.  

[Malcolm Needs ☆]

I agree with an awful lot of what you have written Mabel (as ever), however, I can confirm that there are extremely rare cases where "enzyme-only" antibodies have caused severe haemolytic transfusion reactions, at least two of which were proved by the International Blood Group Reference Laboratory.  In addition, there have been cases (I remember hearing Malcolm Beck, and also Bill Chaffe, describing a couple several years ago) where no antibody could be demonstrated by any technique, and yet when Rh matched blood was given, no reaction occured, so there was an Rh "antibody" present, but this could not be proved in vitro, but certainly was in vivo!

 

I thoroughly agree that either polyspecific AHG or monospecific anti-C3d should be used when testing the serum sample, as using monospecific anti-IgG would defeat the object!  I know of at least one case of anti-Vel (fatal) that could only be detected in serum.  Sadly, for the patient and his family, this was only demonstrated post mortem.  It could very well be an antibody that can only be detected in serum.

 

The other thing that crossed my mind is an antibody within the Dombrock Blood Group System - although these often, but not always, appear in a mixture of antibodies - our anti-DOLG was a single specificity, for example.  These are notoriously difficult to work with, even for Reference Laboratories, "disappear" very easily, but their ability to cause reactions, despite their low "strength" is frightening.

[LAURIE]

Mechanical damage ruled out?  Transfusion process not suspect in any way?  Infusing with saline only?  Not likely thermal damage to units since it happens repeatedly. IgA, IgE or some other class of antibody? Do any others fix complement so as to cause intravascular destruction? I remember someone telling me once of an anti-E that killed a patient that they couldn't get to come up in any testing except, I think, enzyme. (Now that I think of it I wonder if what they found was an innocuous enzyme-only anti-E that was a red herring.)   What about one of those complement-dependent Kidd antibodies we always worry about but which are pretty rare?  The serum specimen should help but use poly AHG (or anti-complement anyway).  If the blood warmer keeps working, keep using it.  

Mechanical damage has been ruled out. After the first reaction discussed with transfusionist; only saline.

will try serum with AHG...thanks

[Sandy L]

I agree with an awful lot of what you have written Mabel (as ever), however, I can confirm that there are extremely rare cases where "enzyme-only" antibodies have caused severe haemolytic transfusion reactions, at least two of which were proved by the International Blood Group Reference Laboratory.  In addition, there have been cases (I remember hearing Malcolm Beck, and also Bill Chaffe, describing a couple several years ago) where no antibody could be demonstrated by any technique, and yet when Rh matched blood was given, no reaction occured, so there was an Rh "antibody" present, but this could not be proved in vitro, but certainly was in vivo!

 

I have also heard this described, either by John Judd or George Garratty, pehaps both. They were aware of multiple cases where the patient apparently had an antibody in the Rh system (e.g. anti-c, anti-C, etc) and the patient was negative for the corresponding antigen. The patient experienced repeated hemolytic transfusion reactions until it was determined that Rh phenotypically matched RBC's survived just fine.  The antibodies could not be demostrated by any standard technique, but I believe they were able to detect the antibody by special techniques (MMA, antiglobulin consumption assay? ... not sure what?).  You might want to contact George Garratty.

[Malcolm Needs ☆]

Sorry Sandy L, are you suggesting LAURIE contacts george, or that I contact George?

[LAURIE]

Thanks everyone for their input...gave us some things to try....let us know if anything else comes to mind and I will let you know how we make out...

[Sandy L]

Sorry Sandy L, are you suggesting LAURIE contacts george, or that I contact George?

Oh sorry, I was suggesting Laurie contact him.

[Yanxia]

If it is because some antibody can't detected by normal tech(such as enzyme only antibodies or some other), the DAT will be pos or neg?

And if it is because HbS, when transfused too much cells or transfused HbS pos cells ,the hemolysis will become stronger?

Just my guess.

[Malcolm Needs ☆]

Even under such circumstances, the DAT could be negative Yanxia.  I once saw a fatal ABO transfusion reaction where the DAT was completely negative, because all the transfused blood had been haemolysed.  Although the reaction was fatal, only a small amount had been transfused.

[bmarotto]

We had a patient many years ago who had repeated intravascular hemolysis during or after most transfusions.  No antibody was detected by us or our Red Cross reference lab.  I phenotyped the patient and each transfused unit and suspected anti-C.  Samples were sent to George Garratty's lab and they detected anti-C reactive using manual polybrene testing.  

[galvania]

Did you ever manage to find out anything about her 'anaemia'? she seems to be receiving a lot of blood. Why do I get the impression that there's a big piece of the jigsaw puzzle that's missing because they are not telling you something?

[EDibble]

Did you ever manage to find out anything about her 'anaemia'? she seems to be receiving a lot of blood. Why do I get the impression that there's a big piece of the jigsaw puzzle that's missing because they are not telling you something?

This is often a frustration we have here Anna. It would seem like a good idea to get a handle on just what is causeing her "anaemia", and not just throw a bandage (transfuse units) on the problem. ESPECIALLY when she is reacting so often to transfusion.    

[vk008]

You said the DAT was negative, what reagents and methods did you use? Have you done the DAT with Anti-IgM cold?

And what drugs is she on?

[Yanxia]

I remember at library of this set, there is an article mention the SCD patients sometimes has  Hyperhaemolysis syndrome,when transfusion , the hemolysis occur , can destroy the transfused cells and the autologous cells with antibodies or without antibodies.

The mechanism is unknown.

[Yanxia]

The article is presemt by Malcolm, thanks.

It is Blood Transfusion Therapy for Haemoglobinopathies.

I think the case looks like hyperhaemolysis.

[RR1]

On a similar theme, is it possible that hyperhaemolysis could be slightly different in a patient with sickle cell disease to one without this? ie, the Hb does not fall lower than the pre-tx Hb?

 

Also, could hyperhaemolysis be a result of the actual haemoglobinopathy- and the fact that many of these patients are on hydroxyurea?

 

I know of a patient that has haemolysed units transfused- but the Hb remains at the same pre-tx level. Investigations by the NHSBT reveal -no atypical antibodies by IAT, but there is said to have an auto-S (like) antibody by Enzyme. Even U- units have been transfused- but Hb is still not being maintained.

 

I think the next step is to transfuse using non-selected units and cover with IVIg. Lets hope this helps.

 

many thanks