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pre-conception antibody titer request


L.C.H.

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We have a woman with a complicated history who is trying to conceive. She has h/o many transfusions and is followed by heme (for anemia) and repro endocrinology.  She is B pos with anti-C, anti-Jka, anti-S.  The prospective father has been genotyped for the corresponding antigens and is c/c, Jkb/Jkb, and S/s.

The clinicians want us to titer her antibodies now, before she has conceived. This isn't something we typically do; our docs usually start titers at the first prenatal visit.  We havent been able to get a good reasoning out of the clinicians about why this makes sense to do in this particular patient (and I am leery of letting a bad habit get started), although I do admit she is very complicated.  

I will be pushing back on the Jka and the C, since dad is antigen-negative. But I may have to give in on titering the anti-S, since he does carry it, and I cant point to any reference that gives a good reason not to.

Any thoughts/info/experience?

 

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Two reasons.

The first is that severe HDFN caused by anti-S is very, very rare, but it does happen.

The second, and much more importantly, is that a titre is a snap shot that tells the obstetrician ABSOLUTELY NOTHING in isolation.  Supposing the titre is, for example, 512, the pregnancy can be monitored (as it can be anyway, whatever the titre) and there can be clinical intervention, if required.  On the other hand, supposing the titre is 2, what does that mean prior to conception?  Again, the answer is ABSOLUTELY NOTHING.  The baby may not inherit the GYPB*S gene from the father, so the antibody will not increase in titre, or the baby may inherit the GYPB*S gene, but that doesn't mean the titre will automatically rise during the pregnancy, although, of course it can.

It sounds to me that the clinicians are fishing, but without either a rod or a net (they haven't got a clue)!

I know that the UK Guidelines do not apply in the US, but it might be worthwhile suggesting that they at least read "British Committee for Standards in Haematology (BCSH): White J, Qureshi H, Massey E, Needs M, Byrne G, Daniels G, Allard S.  Guidelines for blood grouping and red cell antibody testing in pregnancy.  Transfusion Medicine 2016; 26: 246-263 (doi: 10:1111/tme.12299) and/or Royal College of Obstetricians and Gynaecologists (RCOG).  The management of women with red cell antibodies during pregnancy.  Green-top Guidelines No.65; May 2014.  https://www.rcog.org.uk/globalassets/documents/guidelines/rbc_gtg65.pdf.

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I would say, like all pre-natal atypical antibodies, they are thinking ahead to see if a particular titre increases.  One would need a baseline to do this, and they already know the patient will produce antibodies.  I would hazard that a significant increase in titre would suggest a feto-maternal bleed, which for this patient, would need to be dealt with as soon as possible.  (There is no "S" equivalent to things like Rhogam...)

Scott

 

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Okay Scott, but can either the clinician, or you, tell me what constitutes a "significant increase"?  Surely, the absolute titre is much more significant than an increase?  I am not for one moment decrying an increase, that is certainly important, but we also need to know at what titre the anti-S becomes clinically significant in pregnancy.  In the original report involving fatal HDFN (Levine P, Ferraro LR, Koch E.  Hemolytic disease of the newborn due to anti-S: a case report with a review of 12 anti-S sera cited in the literature.  Blood 1952; 7: 1030-1037) the authors state that the titre was between 64 and 128, BUT, it is very important to remember that this was only seven or so years since the IAT was first described, when the sensitivity of the test was, shall we say, primitive, usually involving tile techniques and an AHG made in sheep, goats, rabbits, etc.  The evidence is, therefore, not 100% reliable.

I would have thought that, in this day and age, it would be much more reliable to monitor any pregnancy by such techniques as ultrasound/MCA Doppler, than by the antibody titre, when we do not know what titre is clinically significant in the first place.

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thank you Malcom and Scott for you responses!

We spoke with the clinicians, who seem to understand the anti-S titer number will not tell them much of anything, and they had already realized the Jk and the C were useless to titer (which saved us a lot of grief).

They could not provide any references or good reasons for needing the anti-S now, but pretty much insisted, and we acquiesced on this patient ONLY since her situation is quite unique. So we are treating the clinician rather than the patient this time; I've been covering clin path long enough to know that sometimes this is just the way it goes. Anyhow, we have at least opened a line of communication to the clinicians in the case and they feel we are trying to help them (even if we think it's silly), and that may be all the reassurance they need.

And was better to know about this patient sooner rather than later, b/c if she does make it all the way to delivery with a chronic anemia we were gonna need to plan for her anyway. At least she's now on our radar in BB.

Again, thank you all for your expert opinions!

LCH   

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