The patient is a previously healthy 6 year old male who now is suffering from meningitis.  He was admitted to our facility about a week ago.

Today I received a sample and orders for a type and screen and DAT.  Anti-A 4+, anti-B 4+, anti-D 4+, A1 cells 0, B cells 0, IAT neg, DAT 1+ with Poly and IgG, negative with C3. 

Eluate was negative with all of the O panel cells, 1+ with A1 cells and micro pos with B cells.

 

This patient has never had a transfusion.

 

What could explain these results?

Is the patient on a cephalosporin (especially 2nd or 3rd generation) or penicillin family antibiotic? I would suspect a drug related warm autoantibody. If that's what is causing the problem, the eluate would react with cells coated with the implicated drug (the autocontrol) but would remain non-reactive in the absence of the antibiotic (your antibody screen and panel cells). I've seen a couple of cases in adults that caused severe hemolysis. One was an OB with premature rupture of the membranes and one was a male with pneumonia. Both became severely anemic. I've also seen a case in a child with a viral illness who developed a secondary infection and was treated with antibiotics. In all 3 cases the antibiotic used was cefotetan. In addition, we've seen other patients with cephalosporin related antibodies that didn't really show much (or any) hemolysis. There are cases of fatalities related to antibiotic associated antibodies. If this is what is going on with your little guy, he needs to be taken off of the antibiotic pronto and should not receive the drug again.

 

Some viral infections can also cause a positive DAT all by themselves. Mono and mycoplasma pneumonia come to mind. I've seen a patient with the mumps with a positive DAT - he wasn't on antibiotics or any other drug known to cause a positive DAT, so that left mumps as the most logical explanation. If the meningitis is viral, that could be the problem.

The antibody(ies) have a specificity, though.  I eluted off anti-A and anti-B.

Sorry, I missed the anti-A1 part. Have you subgrouped him? Is he A2B or some other? Did you think to try the eluate with fetal cells? I'm still inclined to think it's an autoantibody that is showing some speficity.

 

Malcolm.....what do you think???

Not at the moment, but I am thinking!

I did not subgroup him.  And really I don't know if it's anti-A1 or anti-A because I didn't test the eluate with A2 cells.  So.. oops.  But his eluate also reacted with B cells. 

 

I actually did get a satisfactory explanation for this from an SBB I work with, and seconded by our pathologist, but I'm gunna let you guys keep guessing and see if anyone gets close.

Has this patient received IVIG or something similar?

No transfusions includes no out of group platelet transfusions, right?  I did see an auto anti-A1 once. I'm voting for IVIg.

Yup. IVIG. 

We're giving him group O rbc's until his DAT is negative.  If he needs a transfusion, which he might, since he has hemolytic anemia from the IVIG.

Ah, then I think there is your answer.

 

IVIG is a sort of soup, with all sorts of antibodies in it, including anti-A, anti-B and anti-AB.  In one case in the UK, at one stage, when these antibodies could be present in quite high titres, this was the cause of prolonged red cell apalasia in an ABO mismatched stem cell recipient.  Within the UK, these "allowable" titres have now been reduced, but the antibodies are still there in small amounts.

 

Elution can be a very sensitive technique (adsorption and elution is used, for example to tell the difference between someone who genuinely lacks a high incidence antigen, such as Lan, and those that express the antigen extremely weakly; too weakly to detect by normal serological techniques) and so any anti-A, anti-B and/or anti-A,B in the IVIG is likely to sensitise your patient's red cells and you would be able to elute them back off.

 

In a way, it is the same as the prophylactic anti-D immunoglobulin that is given antenatally that can sensitise a D+ baby's red cells, but is too weak to cause HDFN.

 

I would be extremely hesitant to "diagnose" a haemolytic anaemia from your evidence bloodbankninja.  At best, from your evidence, you have a case of a serological transfusion reaction, unless the child requires a transfusion, and, even then, the requirement for a transfusion may be coincidental, due to the underlying pathology.

 

Good call R1R2.

Ah, then I think there is your answer.

 

IVIG is a sort of soup, with all sorts of antibodies in it, including anti-A, anti-B and anti-AB.  In one case in the UK, at one stage, when these antibodies could be present in quite high titres, this was the cause of prolonged red cell apalasia in an ABO mismatched stem cell recipient.  Within the UK, these "allowable" titres have now been reduced, but the antibodies are still there in small amounts.

 

Elution can be a very sensitive technique (adsorption and elution is used, for example to tell the difference between someone who genuinely lacks a high incidence antigen, such as Lan, and those that express the antigen extremely weakly; too weakly to detect by normal serological techniques) and so any anti-A, anti-B and/or anti-A,B in the IVIG is likely to sensitise your patient's red cells and you would be able to elute them back off.

 

In a way, it is the same as the prophylactic anti-D immunoglobulin that is given antenatally that can sensitise a D+ baby's red cells, but is too weak to cause HDFN.

 

I would be extremely hesitant to "diagnose" a haemolytic anaemia from your evidence bloodbankninja.  At best, from your evidence, you have a case of a serological transfusion reaction, unless the child requires a transfusion, and, even then, the requirement for a transfusion may be coincidental, due to the underlying pathology.

 

Good call R1R2.

That's why they pay me the big bucks!  NOT!!! 

I'm not the one who decided he had hemolytic anemia from the IVIG.  That was the pathologist.

He looked at the patient's other results like the haptoglobin and decided that the patient had some hemolysis. 

There is another possibility but it depends on your A and B cells coming from a different supplier than your panel cells. It could still be antibiotic-related, with the offending antibiotic being present in your A and B cells but not in your panel cells.

I'm not the one who decided he had hemolytic anemia from the IVIG.  That was the pathologist.

He looked at the patient's other results like the haptoglobin and decided that the patient had some hemolysis. 

 

Point taken!!!!!!!!!!!!!!!!!!!!

Anna,

 

Would you likely see that effect in an eluate?  The antibody that is reacting with the antibiotic in the reagent cell diluent would have to have been attached to the patient's cells.  Has anyone ever seen a drug-induced antibody elute off and then react with reagent cells?

Good question, Mabel.  I don't know.  Malcolm?

Well, Anna, it was the reactions with the eluate that convinced me that IVIG may be involved (once R1R2 had suggested the idea - I'd didn't even think about it myself).

 

Both the A and the B cells reacted with the eluate, but not the group O, suggesting that there may have been an element of anti-A and anti-B present (and/or anti-A,B in the patient's plasma.  Whilst I see from where you were coming with the antibiotic (and I have seen this myself in plasma samples with anti-antibiotic and red cells stored in a solution containing an antibiotic), the fact that the eluate did not react with the group O cells, but did with the A and B cells seemed to suggest the presence of a genuine blood group antibody (or antibodies) that suggested to me that this was not a case of anti-antibiotic - if you see what I mean!

Edited May 17, 201312 yr by Malcolm Needs

This reminds me of a case many years ago, when an Rh pos patient with ITP needed a rbc transfusion. Hmm, strongly positive Autocontrol and then DAT. Eluate was anti-D. Even after several phone calls no one in the office saw fit to mention that the patient was being treated with WinRho.    

 

Beth

Removed

Edited June 3, 201510 yr by RollSlow10