Malcolm Needs

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Welcome.

The simple answer is gagpinks, but this is the answer I have just received from my friend at the IBGRL (who shall remain anonymous for now). The question I put was as follows: "Sorry to bother you yet again, but I have had a query from a friend. I think I know the answer, but I wanted to check with an expert. If a pregnant lady has an allo-anti-D, can this affect cffDNA harvesting from the mother's circulation? I don't think it does unless the anti-D knocks out all of the foetal red cells. Best wishes from this bloody nuisance, Malcolm" Answer below. "Hi, that's right, anti-D makes no difference to the cffDNA test. The two biggest problems are false negatives due to insufficient RHD gene in the test sample and mums with a RHD gene (despite pheno typing as D-) leading to strong positive results. Take it easy." As I said, the friend will remain anonymous for now, but, suffice it to say, he/she is one of the people who do the test, so I think the answer can be trusted!

Thanks. No, that shouldn't make any difference.

Not as far as I know, but I will check for you (but, apologies, it will have to be tomorrow now).

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This may not be easy/possible to do, but have you checked that the patient had not been given a very large dose of anti-D immunoglobulin during her first pregnancy? It is not totally unknown for a woman to develop an allo-anti-D in her first pregnancy, although it is incredibly rare, but, if the patient had an abdominal trauma, she could well have been given a very large dose of anti-D immunoglobulin. This may explain why her antibody screen was negative at 12 weeks of gestation in her second pregnancy. There is also the (vague) possibility that the anti-D in the patient's circulation first pregnancy MAY have been a mis-identified anti-LW. I must confess that I am slightly at a loss as to why the 15 week sample could not be used for foetal RHD genotyping, leading to a prediction of the D antigen expression on the foetal red cells, unless all the foetal red cells had been cleared from the maternal circulation. If this is the case, there are still other ways of obtaining foetal DNA (albeit more dangerous), such as foetal reticulocytes in the amniotic fluid. If the "anti-D" is only "enzyme-reactive", it is true that it would be impossible to quantify, but it is also most unlikely to be clinically significant in terms of HDFN (but I wholeheartedly agree with you that it should be monitored throughout the pregnancy). I take it that the first pregnancy resulted in a successful delivery of a healthy baby?

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I would most strongly advise you to send a sample, possibly even multiple samples throughout the pregnancy, to a Reference Laboratory. As the patient is pregnant, there is the possibility that the Jk(a) antigen you are detecting is actually being expressed on the red cells of the foetus, and you are detecting it as a result of a foeto-maternal haemorrhage. However, the Jk(a) antigen is not necessarily straight forward, as there are weakened forms of the antigen (and the Jk(b) antigen come to that) where there are amino acid substitutions remote from the site usually associated with the Jk(a) and Jk(b) antigens (280 of the mature protein). In addition though, you have, obviously, to consider the health of the unborn baby who, even if the antibody does turn out to be a maternal auto-anti-Jka, may cause haemolytic disease of the foetus and newborn, albeit this will usually be be very mild. I attach a PowerPoint which may, or may not help you in your decision to send a sample to your local Reference Laboratory (also tell them the ethnicity of the patient). Interesting case - please keep us informed. In Depth Lecture on The Kidd Blood Group System.pptx

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