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anti-C or anti-G in RhIG?


Mabel Adams

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We have a gravida 1 para 0 at 12 weeks that has been given RhIG twice for *** bleeding (50 micrograms 12/4/12 and 300 mcg 1/14/13) and on 1/15/13 they drew a sample for her prenatal panel. Her plasma appears to contain anti-D in a strength that is consistent with passive anti-D but she also has a 1+ positive reaction (gel) with 3 C pos cells. (All other antibodies ruled out.) No record of any previous antibody screens.

Can RhIG contain anti-G and/or anti-C as well as D? I swear this topic is on this forum somewhere but I couldn't find it. I guess we have to treat it like it is a real antibody at this point, but I want to be sure my idea that it could be passive is right.

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As far as I know Mabel, and I do mean as far as I know, these days anti-D immunoglobulin should only contain anti-D (with, obviously, the chance that there may be the odd antibody present directed against a low frequency antigen, which nobody could be expected to detect under "normal circumstances".

As far as I know, other extraneous specificities are no longer allowed in this blood product.

It is very unusual for an antibody, stimulated by pregnancy, to be detected in the first pregnancy, but this poor lady seems to have had quite a traumatic time, and the antibodies could be true alloantibodies, rather than "passive" antibodies.

Incidentally, do the C+, D- red cells react more strongly with the lady's plasma than do D+, C- red cells that may lead you to suspect anti-G? If not, then it is probably anti-D+C, and more probably alloantibodies.

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Since she has received 2 doses of RhIG recently the anti-D is a strong 2+ (in gel). The anti-C is a slightly weak 1+. If she had made anti-G, I would think that the passive anti-D would increase that titer enough that the usual pattern of strengths might be masked. I did find a current drug insert for RhIG that states that trace amounts of anti-A, B, C or E may be detectable in patients that have had RhIG. It was talking about when it is given IV but this lady's blood was drawn 14 hrs after getting the dose so I thought, even though given IM, these weak antibodies might show up in her sample at least for awhile. I think we just have to see if the anti-C disappears over time and err on the side of caution. We are titrating the anti-C but doubt that it will be detectable in our tube saline titer method. I appreciate any corrections if my thoughts are not on the right track.

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No, you are absolutely right about the "ratio" of anti-D and anti-C masking a normal anti-G reaction (if you see what I mean - probably could have put that better, but I know what I mean)!

That having been said, the way the IV anti-D immunoglobulin is produced is very different to the way the IM anti-D immunoglobulin is produced, and I would be amazed if you could detect anti-C that quickly from IM anti-D immunoglobulin - the key being in the word "trace", because it takes time for the body to absorb the anti-D (plus extraneous specificities) from the muscle into the circulation.

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Mabel,

I checked the package insert of the RhIG that we administer (Phophylac) and it says "Rhophylac can contain antibodies to other Rh antigens (e.g. anti-C antibodies) which might be detected by sensitive serological tests following administration." I would find out what product was used and check the package insert. I do think that the RhoGam insert says something similar.

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We have not done the validations for gel titers. It would require educating all of our physicians that a titer of 16 does not mean the same as they are accustomed to. There are no perinatologists here so patients get referred out so we would need to notify them as well and make sure that they understand that our titer numbers are not the same as the ones where they are. Because OB guidelines usually list a specific titer without clarifying the technique, we would have to teach them to trust our comments on what is a significant titer rather than the publications they are accustomed to. It appears that gel titers run about a dilution higher than saline tube titers. Someday, we will tackle this. I'd be happy to hear from other smaller regional hospitals how they proceeded in making the change to gel titers.

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Just curious.. The small hospital I am now at doesn't do titers, antibody work-ups, antigen typing or other "complicated" testing. I'm am moving to change some of that but even some of the larger labs around here do not do titers (though the one I came from did them in gel). So titers will not be high on my list, but I have convinced the higher-ups to let me get a panel so I am making progress.

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We have a gravida 1 para 0 at 12 weeks that has been given RhIG twice for *** bleeding (50 micrograms 12/4/12 and 300 mcg 1/14/13) and on 1/15/13 they drew a sample for her prenatal panel. Her plasma appears to contain anti-D in a strength that is consistent with passive anti-D but she also has a 1+ positive reaction (gel) with 3 C pos cells. (All other antibodies ruled out.) No record of any previous antibody screens.

Can RhIG contain anti-G and/or anti-C as well as D? I swear this topic is on this forum somewhere but I couldn't find it. I guess we have to treat it like it is a real antibody at this point, but I want to be sure my idea that it could be passive is right.

Mabel, we use Rhophylac. Once in a while a vial will outdate and I'll dilute it a bit and let the students have at it. That r'r cell has always reacted, so I'd say there's anti-C and/or G there. Feel like sacrificing a vial (preferably same lot) and doing a panel on it?

Oops, just got to the rest of the posts and see I'm not the only one suggesting this...................

Edited by Dr. Pepper
I read the rest of the posts!!!
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This is from the Winrho package insert:

"After administration of WinRho® SDF, a transitory increase of various passively transferred antibodies in the patient’s blood may yield positive serological testing results, with the potential for misleading interpretation. Passive transmission of antibodies to erythrocyte antigens (e.g., A, B, C and E) and other blood group antibodies [for example, anti Duffy, anti Kidd (anti JKa) antibodies]5 may cause a positive direct or indirect (Coombs’) test."

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I would be interested if anyone else has observed this in a patient. We have a prenatal clinic where we dispense Rhophylac but do not have labor and delivery, so we never get to test the Moms while they still have the RhIG in their system. The times we do find a passive RhIG anti-D, we have only seen anti-D. As I said earlier in the thread, we have seen anti-C/G when testing the RhIG itself, so it seems reasonable that you should be able to pick it up passively as well. It might be fun to titer the anti-D and (let's call it) anti-C from the Rhophylac. Perhaps the anti-C is in a low enough titer that it can't be detected after you mix it up in the mom a bit.

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The only time I've seen anything like this in a patient over the 30+ years I've been working, other than anti-D with RhoGAM, was a couple of patients with antibodies apparently from receiving IVIG (sorry, can't remember antibody specificity off the top of my head). If you don't draw the right patient at the right time, you probably miss a lot of those kinds of antibodies even if they are there. It would be kind of interesting to know how frequently this phenomena occurs.

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