Amemia secondary to MDS

[WCHBB]

I need help. I have a lady that comes in usually ever month to get 4 units of paced cells, amemia secondary to MDS. Monday she came in and as usual she typed A postive antibody screen gel negative, units gel negative. She came back yesterday and received 2 units no problem but while receiving the 3ed unit she went to the bathroom and called the transfusion nurse because she had blood in her urine. The unit was stoped vitals taken and she had a 2 degree increase in her temp. She had no complaints,felt fine. In 2006 she said she had an anphylactic transfusion reaction (she lived in Clevland, Ohio then and nothing was found wrong to cause this reaction) and this was nothng like this. Her physician was notified and later she was released (I was off yesterday). I repeated everthing that was done yesterday pre and post samples, DAT etc. all are negative BUT the post sample is hemolyzed (drawn x2 to verify).This am I have spoken with the nurse and ever time she comes in she will give off an acid smell (not fruity) after getting her second unit. ?? I have never had anyone tell me this before. Her units are giving through her port. The transfusion nurse has called her this am and her urine has just a ting of blood in it but she had fever, chills and nausa last night.

What do you think has cause this and what do I need to do? I want to know what her BUN and cret are along with her H&H I also feel she needs to be worked up by our ARC referance lab. Is this what you would do? Thanks for any help you can give me. Cyndie

[vdvictory]

Did you do a gram stain and culture of the blood bag?

[tricore]

Draw a new specimen and send it and the pretransfusion specimen to the reference lab. Sounds like a patient I had years ago. He had an anti-K1 that was detected a few days after the reaction and was never demonstarted after that. Could not pick it up in the pretransfusion specimen despite using several different techniques.

[Lcsmrz]

Not all hemolytic episodes are immune mediated, but that sure is suspicious.

Any chance that the unit was hemolyzed due to mishandling, port problems, concurrent IV solution incompatiblity, etc? Also, were there intact RBCs in the urine, as in bleeding instead of hemoglobin clearance?

You may find an antibody finally showing itself with the next crossamtch event.

[WCHBB]

There where no red cells in the urine. She came back yesterday and her plasma is now back to normal her DAT is still negative. I just checked and the culture on the unit is negative. I guess we may never know what caused this. Thanks to everyone for your help. Cyndie

[Penny Thiel]

Don't break your head over it, Cyndie. There will always be things that you're just gonna have to let go of. We had a lady a few years ago who came in for some sort of anemia, be transfused her and wow and wow, she had this massive reaction. I'm tellin ya, in her spun blood bank tube you could literally not tell the difference between her cells and plasma. All of it was RED!

A huge who-ha followed and we turned her every way but loose! EVERYTHING was negative including testing for PNH. The whole hospital was stymied! Her hemoglobin was holding around 5 and you know what? She left AMA and we never heard from her again. This is a small town and something like that is most bizarre.

So, be blessed that you and your crew did nothing incorrectly, put the experience in your "Little Known, Well Known Facts" file, smile and go about your day.

With a smile,

Penny

[WCHBB]

Thanks I'm feeling better today about this but you made me laugh. Cyndie

[bmarotto]

We had a patient years ago that started having hemolytic reactions similar to what you describe. Testing using multiple methods was always negative. I did a red cell phenotype using patient reticulocytes and also phenotyped several units that he had a reaction to and one he did not. I found the patient and the unit that he did not react to were big C negative. The other units were big C Positive. We sent his blood out for polybrene antibody testing and they confirmed the presence of anti-C. If your patient continues to have reactions you may want to try phenotyping if her screen continues to be negative. Otherwise, it could be due to an antibody to a low frequency antigen. As others have said, you may never know the answer.

[tricore]

Cyndie,

Are you sending it to the reference lab? Please let us know what you find on this patient.

[David Saikin]

As bizarre as this sounds . . . we had a patient who had hemolytic reactions if she was transfused under fluorescent lights. Transfuse her in the dark, no problem . . . with the lights on - hemolysis!

[clmergen]

I knew fluorescent lights were evil, but not that bad. And I do believe it.

[WCHBB]

No we did not send it out the reference lab said that if her DAT was negative I did not need to send it. She is doing great now BUT she still needs to come back and get more units. She said(the patient) when it happend before in Ohio that the big teaching hospital could not figure it out so I guess we may never know. The culture on the unit never grew out and her plasma/serum is now clear. Thanks to everyone for your help. Cyndie

[tricore]

My patient also had a negative DAT. He had hemolyzed all of the donor cells. He was an outpatient transfusion who went home and had chills, fever, and red urine that night.

[AMcCord]

These kind of patients always make you pray that they'll move far far away so you don't have to deal with the problems, don't they!?

I think I'd consider trying phenotypically similar red cells for her next transfusion, running that first 25-50 mls sloooowly to see if anything is going to happen, then continue infusing the rest of the unit slooowly, if all seems OK. Let one unit sit and circulate for awhile, check DAT, check for hemolysis, rise in Hgb, etc. If she is doing well, try another unit, slow, slow, slow. If she had an undetectable antibody (in spite of everyone's best efforts) like the anti-C or anti-K1 previously mentioned, a phenotype matched unit MIGHT work if her antibody is directed at one of the antigens we can routinely screen for. The literature discusses in vivo red cell survival studies with 51Cr tags for cases of mystery hemolysis, but that sure isn't practical for those of us in smaller facilities. Is she is hemolyzing ALL the transfused red cells rapidly?? then her DAT is going to be negative, because she's destroyed anything coated with antibody. That would sound like an antibody to a high incidence antigen - scary to think a patient could have that and not be able to detect the antibody. Does she have siblings? A sibling can sometimes be compatible in difficult cases.

Have you asked the large hospital's blood bank what they transfused and if anything they tried worked better than anything else? Have you consulted with the medical director of your blood supplier or reference lab to see if they can recommend anything? Just throwing out ideas here............I wish you and your patient luck!

[Malcolm Needs ☆]

There is a possibility that this could be a case of hyperhaemolysis? This is most often associated with sickle cell patients, but we are aware of at least one (unfortunately) fatal case of hyperhaemolysis in MDS.

Normally, in such cases, you will find that the Hb is lower after transfusion than before, but with low reticulocytes, and with hyperactive macrophages.

In such cases it's best not to transfuse, but if there is no alternative, it is best to transfuse under IVIG and methylprednisolone.

It's only a thought. I may well be barking up completely the wrong tree, but it is worthwhile ruling this out.

[David Saikin]

Could this be due to an IgA mediated antibody?

[Cathy]

We have seen a similiar case, sent it to the Reference Lab and they had no answers either. Please keep us posted.

[Malcolm Needs ☆]

Could this be due to an IgA mediated antibody?

Hi David,

Whilst I would agree that IgA mediated antibody reactions can be both dramatic and life-threatening, would you;

a) expect to see haemoglobinurea?

and

expect such an antibody to have been demonstrated much earlier in the patient's life-history?

I am genuinely asking questions here, rather than questioning your answer (if you see what I mean)!

[heathervaught]

This would be an interesting case to send through Bio Array testing, given the recent transfusion history (much easier than typing retics!!!)

I was also curious -- if a patient usually hemolyzes the 2nd unit (or whatever), then is there a possibility that the RBCs being hemolyzed are the patient's, in response to the acid levels present in the anticoagulant/additive? Perhaps an osmotic fragility study on the pre-transfusion sample would provide insight?

[Malcolm Needs ☆]

I would agree with heathervaught that genotyping the patient would be far easier than trying to type the reticulocytes. For one thing, the patient's reticulocytes would not necessarily exhibit the same antigens (or, at least, antigen strengths) as the patient's red cells, as some antigens need time to mature as they go through the bone marrow (usually those antigens with a dominent sugar residue, as the rpotein antigens will be there anyway).

I would disagree, however, that it could be the acidic nature of the anticoagulant. Whilst this could possibly so in cases of massive transfusion (according to the literature), it is highly unlikely that the natural buffering within the patient's plasma would be affected by just two units of blood (with the caveat that the patient may, of course, be of extremely small stature, making this slightly more possible, but still unlikely).

[bbbirder]

Someone else asked this, suggesting that this is non-immune hemolysis... could the unit have been mishandled (stored in an unmonitored refrigerator)? was the patient getting other infusions at the time? etc.

Linda Frederick

[David Saikin]

I would expect hemoglobinuria if there was complement activation, but the sources I have checked say that IgA does not activate the classic pathway. Should it have been detected earlier? . . . I don't know how, unless you use an antiglobulin with IgA specificity (they do exist).

[Malcolm Needs ☆]

Thanks David,

That's rather what I thought re IgA not causing haemolysis.

You are, of course, absolutely correct about most AHG not containing anti-IgA. The DAT cards supplied by DaiMed contain one column containing a monospecific anti-IgA, but their routine DAT cards used by most hospitals only contain either anti-IgG+anti-C3d or only anti-IgG, and so it is unlikely (almost impossible) that such an antibody would be detected by routine antibody screening or routine antibody identification. One would only get a clue by performing a DAT with the rather specialised DAT cards used (almost exclusively) by a Reference Laboratory.

Then, of course, one would have to identify the specificity using a decent monospecific anti-IgA by IAT. A knotty little problem........................!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

Edited April 27, 2009 by Malcolm Needs
Missed out a vital word! Fingers well faster than brain!!!!!!!!!!!!!!!

[RR1]

There is a possibility that this could be a case of hyperhaemolysis? This is most often associated with sickle cell patients, but we are aware of at least one (unfortunately) fatal case of hyperhaemolysis in MDS.

Normally, in such cases, you will find that the Hb is lower after transfusion than before, but with low reticulocytes, and with hyperactive macrophages.

In such cases it's best not to transfuse, but if there is no alternative, it is best to transfuse under IVIG and methylprednisolone.

It's only a thought. I may well be barking up completely the wrong tree, but it is worthwhile ruling this out.

Hi Malcolm,

Of the three post -tx hyperhaemolysis patients (all SCD) I had at my previous lab each had additional red cell antibodies as well- is this generally the case ?

Also could hyperhaemolysis be a feature of any drug regime they were put on for their condition ?

p.s I think the Diamed gels are called Provue in the U.S...but I may be wrong!

Edited April 27, 2009 by RR1
forgot

[Malcolm Needs ☆]

In my own (limited) experience of cases of hyperhaemolysis, it is not unusual for atypical alloantibodies to be present in the patient's plasma, but it is by no means a sine qua non. Certainly the MDS case I quoted had no alloantibodies detected.

Perhaps I should stress a little more than I did that the most common cases of this extremely rare condition are seen in multiply transfused cases if sickle cell disease; but then it is also not unusual for individuals who have sickle cell disease to be multiply transfused, and therefore make alloantibodies. It could well be that these antibodies are red herrings, particularly as you would give antigen negative blood.

I know of no drugs that are associated with this condition, which is a problem, as such cases cannot be predicted and come as a nasty shock.