testing FOB for antigens

[L.C.H.]

Hello, all - 

We've been having some back and forth with our MFM department and their handling of maternal antibodies. When the mom has an antibody, they test dad for the antigen, and then stop following if negative, and are resisting any change to this (see below for why i find this a problem). I pulled the ACOG Practice Bulletin 192, March 2018 and indeed that is the standard of care per ACOG (although there was NO reference for that entire section of the paper, so i dont know where that info came from).

However, we had a case (with MFM) earlier this year where mom had an anti-E on her initial T+S, and they tested dad, dad was negative, so they stopped following.... Then six months later just before delivery we find an anti-c with a roaring titer, with a problematic outcome. So I am kinda not OK with just testing dad and letting it all go when it comes to Rh antigens. Any words of wisdom here? I am going to be tangling with MFM over policy in the new year, and this is certainly on the docket. 

thank you - 

 

[Malcolm Needs ☆]

In the UK, we tended to only perform typing on the putative father, if the maternal antibody specificity was one (or more) of anti-D, anti-c and/or anti-K, unless another antibody, known to cause clinically significant HDFN, AND with a high titre (sometimes taken as 32, but, in practice, usually a titre of 128 or more).

Nowadays, certainly within the UK, and, I think, also in The Netherlands, if the maternal antibody specificity is one of anti-D. anti-c and/or anti-K we tend to send a sample of the maternal peripheral blood to the International Blood Group Reference Laboratory in Filton, Bristol, for cell free foetal (cff) DNA testing, to see if the foetus carries the appropriate genes, leading to expression of the antigens on the foetal red cells (this can also be performed for (in shorthand) the RHC, RHE and RHe genes, if felt necessary.  These tests for foetal genes are CE marked, but other genes, for example, FYA, cannot be tested in this way (although foetal cells harvested from amniotic fluid can be tested).  This testing of cffDNA, circumnavigates the problem of the putative father not actually being the biological father, and, of course, cases of donated eggs and sperm from a third person.

Within the UK, this testing is now embedded in various Guidelines, such as 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 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, and these have been bolstered by the approval of National Institute for Health and Care Excellence (NICE).

I am aware that (at least, the last time I heard) this genetic testing may not yet be allowed in the USA (this may now have changed).

[John C. Staley]

First off, what is MFM and FOB?  I don't think you want me guessing!  

Secondly, the guidelines coming from someone who has little knowledge is not just foolish it's potentially dangerous.  It is not uncommon for the husband, mate, partner or most recent paramour to NOT be the biological father and to assume so has the potential of severe consequences.  There is no need to make an issue of it with the mother, just do the testing in the background if the physician is smart enough to understand this.  

Edited December 18, 2019 by John C. Staley
I wanted to.

[L.C.H.]

oops, John C. Staley - sorry for the abbreviations!  

MFM = maternal-fetal medicine; FOB = father of baby

[Baby Banker]

3 hours ago, L.C.H. said:

oops, John C. Staley - sorry for the abbreviations!  

MFM = maternal-fetal medicine; FOB = father of baby

I wondered if you were testing fecal occult blood.

[L.C.H.]

ahh, i've been at a specialty hospital for too long, i forgot FOB is also fetal occult blood.  :-)

[L.C.H.]

Malcolm, thank you for the article! I hope to get to it today.

It appears cff DNA testing is available in the US for some things (DiGeorge, for instance), but I am not readily finding a lab that offers RHCE testing. Am going to keep looking.

I guess my main concern is that since anti-c can kick up later in pregnancy, if we see an early anti-E in mom, should we advise to 1) test dad (or fetus with cff if i can find it) for not just E but also c antigen and/or 2) request an additional screen later in the pregnancy to see if anti-c has come up? (presuming mom is c-negative)

 

[Malcolm Needs ☆]

2 hours ago, L.C.H. said:

I guess my main concern is that since anti-c can kick up later in pregnancy, if we see an early anti-E in mom, should we advise to 1) test dad (or fetus with cff if i can find it) for not just E but also c antigen and/or 2) request an additional screen later in the pregnancy to see if anti-c has come up? (presuming mom is c-negative)

 

I must admit that we didn't use to test the father if the mother had an anti-E of low titre, but, perhaps, we should have so done, especially if she was c Negative.