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Hello all, 

We have a patient that has multiple Antibodies (5) and requires a titer. We just recently hired a new tech from another facility and she stated that they would use one cell positive for all antigens (if possible) to do a titer and then if the titer was significant they would split the titer out to identify which antibody was causing the high titer. I am curious to know if any other facilities practice this. Thank you for your input. 

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I remember John Judd once advising me to titrate an anti-M suspected to have an IgG fraction and not worry about separating the IgG from the IgM unless the titer became significant. Then we could titrate it after destroying the IgM if need be to see what the true IgG titer was.  It never exceeded something like 8 so we never had to send it out for additional testing.  These seems something like that--drawing a line of what is safe to save the cost of extra testing. Only do the additional testing when it is no longer safe to avoid it.  You would have to determine how you will turn it out so as to not overly confuse the OB/perinatologist.  "Titer against c, E, Fya, Jkb and S positive cell = 8"? Then next time when it is 16 with a cell of that phenotype, you would repeat separate titrations and results would be "titer against c & E positive cell = 8 & titer against Fya, Jkb and S positive cell = 4"? Or do you then go to separate cells for all of them but the E & c?  Or turn it out as 16 and they quit using titers to monitor?  I can see some logic to moving to ultrasound monitoring as soon as the cumulative titer is above 16 or so but we also like to watch how titers change over time to help us guess which antigens baby is positive for.  If you already tested amniocytes for antigens that would be moot but if you have only serology to go on you could miss some clues.  We titrate E & c together because they are likely to be inherited together and separate E+, c- cells are hard to find.  It also depends on if you can reliably find the same phenotype of cells for the next titration (we don't have the perfect world of using the same specific donor cell for the entire pregnancy).   Maybe it also matters if you know dad's phenotype/genotype.  If he is R2r then baby could be c+ E- but not if he is R2R2.   Sorry to ramble on; surely someone with more experience in this than I can answer with something more substantive but I've enjoyed speculating.  :)

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Heterozygous versus Homozygous expression for the antigen is key especially in the MNS system.  You should know what the status is of the cell you are using so that you can compare apples to apples.

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I would agree with Mabel, above, where the point of the serial titres is to check if things are getting worse (as in a pregnancy). It seems like you would have to isolate it in all cases, including in the initial specimen, even if the titre is low. Otherwise, if on a subsequent specimen one does have a high enough titre to warrant "splitting" it out, you would have nothing to compare that specific antibodies titre to. 

We never have had to deal with anything like this so I also would be interested in what others are doing.

Scott

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We ALWAYS split.

Different antibody specificities have different titres at which they can be clinically significant.

For a long time (in the UK) we used to regard anti-K as clinically significant at a lower titre than any other specificity.  Then, it was thought that, actually, the antibody was not clinically significant until it reached a titre of 32.  The the National External Quality Assurance Scheme in the UK introduced a regular exercise to see how good we were (as the UK) at titrations, and it turned out that we were, to put it politely, complete rubbish!  Since then, we have been getting steadily better, and are now quite good at it.  This has also shown us that our feelings about anti-K were right all along, and that some examples of anti-K actually are clinically significant at very low titres (whilst others are not).  So now, our guidelines state that, if a woman has anti-K, her pregnancy should be screened at least once during the pregnancy at a Foetal Medicine Unit (or similar speciality) ( Royal College of Obstetricians and Gynaecologists (RCOG) The Management of Women with Red Cell Antibodies During Pregnancy.  Green-Top Guidelines Number 65 May 2014, and  White J, Qureshi H, Massey E, Needs M, Byrne G, Daniels G, Allard S.  BCSH (now BSH) Guideline for blood grouping and red cell antibody testing in pregnancy.  Transfusion Medicine 2016; 26: 246-263).

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Malcolm - would you be able to share what happened to "improve" the titers?  What changes were made in the procedure/ cell choices, etc that made them more reliable?  Was it something specific or just more practice?

CAP has introduced a "Universal titer procedure" - but peer results are still all over the place. 

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cswickard, I wish that there was a "magic formula", as it were, but actually, all it was, was that individuals "practised" titrations more avidly,, but, because NEQAS sent out exercises, they were also able to compare their results with others.

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Does anyone know if there is an Antibody Titer QC system on the market?

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On 5/7/2019 at 10:07 AM, galvania said:

what are the antibodies and what is the reason for needing the titration?

If my memory serves me right the patient has 5 antibodies: S, Jsa, V, Fya, and K and she is pregnant. 

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On 5/13/2019 at 9:56 AM, ANORRIS said:

Does anyone know if there is an Antibody Titer QC system on the market?

Either CAP or AABB provide a Titer for intra (and inter) lab comparisons. 

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