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Auto-anti-D?


SMILLER

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We currently have a 50 year old male in house that had an accident that damaged his foot 3 weeks ago.  He arrived septic and has had to have an amputation. 

His ABO/Rh gives a B pos with a 4+ anti-D.  His gel screen and panel give 1+ results that match up with an anti-D (all others rules out). His autocontrol was positive at 1+ by IgG, neg for compliment.  The eluate results matched the original antibody ID.  Presently this patient's specimen is on its way to our reference lab.  Previous history at another facility lists him as B Pos, screen negative.  As far as we know, he has never been transfused.

What are the possibilities (for what appears to be an D auto antibody), and how should he be treated?

Scott

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Given the fact that he has had an infection bad enough to warrant amputation of his foot, I seriously wonder if what you are detecting is an auto-anti-LW, that is mimicking an auto-anti-D?.  There are certainly cases recorded of individuals producing an apparent allo-anti-LW, which, of course, will mimic an anti-D, when, actually, what they have is an auto-anti-LW (and, transiently, they appear to be LW Negative) when, in reality, they are LW Positive and are producing an auto-anti-LW.  For a classic class, see:

Giles C M, Lundsgaard A.  A complex serological investigation involving LW.  Vox Sang 1967; 13: 406-416.

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On 7/1/2019 at 8:31 AM, SMILLER said:

We currently have a 50 year old male in house that had an accident that damaged his foot 3 weeks ago.  He arrived septic and has had to have an amputation. 

His ABO/Rh gives a B pos with a 4+ anti-D.  His gel screen and panel give 1+ results that match up with an anti-D (all others rules out). His autocontrol was positive at 1+ by IgG, neg for compliment.  The eluate results matched the original antibody ID.  Presently this patient's specimen is on its way to our reference lab.  Previous history at another facility lists him as B Pos, screen negative.  As far as we know, he has never been transfused.

What are the possibilities (for what appears to be an D auto antibody), and how should he be treated?

Scott

Hello, Scott, 

I have a few questions about this case. 

1) What is the eluate result that "matched the original antibody ID"? Is it panagglutination or anti-D in eluate? 

2) How many sources of anti-D did you use to type your patient? We use up to 3 or 4 sources in this lab if we have such problem in this lab. 

Here are the things that I usually do to figure out if anti-D is that of auto- or allo- .. 

1) exclude the possibility of RhoGm or IVIG adminstration

2) Perform D typing on the patient's red cells using different sources of anti-D. (we usually have 4 or 5 sources). If D reactivity is found variable positive and negative reactions with different clones, perform genomic testing to exclude partial/variant D antigen. 

3) If the patient is elderly male and recently transfused with D+ blood (or if you see mixed field in the D typing), perform cell separation by density centrifugation, perform D typing and auto control using retic-rich cells. 

4) If the patient is DAT positive, perform EGA or CDP treatment, test EGA, CDP treated cells with plasma and eluate. 

5) Lastly, test plasma and/or eluate (wherever you are seeing anti-D) with DTT-treated red cells and cord cells to exclude or confirm anti-LW. 

Please let me know if there is anything else to add to this list. Hope this is helpful. 

Edited by Bb_in_the_rain
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19 hours ago, Bb_in_the_rain said:

Hello, Scott, 

I have a few questions about this case. 

1) What is the eluate result that "matched the original antibody ID"? Is it panagglutination or anti-D in eluate? 

2) How many sources of anti-D did you use to type your patient? We use up to 3 or 4 sources in this lab if we have such problem in this lab. 

Here are the things that I usually do to figure out if anti-D is that of auto- or allo- .. 

1) exclude the possibility of RhoGm or IVIG adminstration

2) Perform D typing on the patient's red cells using different sources of anti-D. (we usually have 4 or 5 sources). If D reactivity is found variable positive and negative reactions with different clones, perform genomic testing to exclude partial/variant D antigen. 

3) If the patient is elderly male and recently transfused with D+ blood (or if you see mixed field in the D typing), perform cell separation by density centrifugation, perform D typing and auto control using retic-rich cells. 

4) If the patient is DAT positive, perform EGA or CDP treatment, test EGA, CDP treated cells with plasma and eluate. 

5) Lastly, test plasma and/or eluate (wherever you are seeing anti-D) with DTT-treated red cells and cord cells to exclude or confirm anti-LW. 

Please let me know if there is anything else to add to this list. Hope this is helpful. 

1) The original antibody ID matched an anti-D, as did the eluate.

2) Just one source for anti-D testing.  Its a poly-monoclonal blend.

and...

We are pretty sure the gentleman has NOT had any Rh immune globulin.

Genomic testing is, indeed in process, as we have sent the specimen to our reference lab.

The forward reaction with anti-D was a strong and clear 4+.  A partial or weak D is unlikely.

The rest is being processed at our reference lab this week.  I will post results here...

Scott

 

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  • 2 weeks later...

Results of our reference lab testing on this patient makes him out to be a partial-D, specifically DAU-0.  (Nothing about an anti-LW, which is where I was going.)  They note that "patients with a partial RHD*DAU0 allele have not been reported to make anti-D, therefor, this patient's reported anti-D is most likely autoimmune."

The Genotype is: RHD*DAU0-ce(48C) / RHD*03N.01-ceS.

Also they found that the patient is homozygous for the "Duffy null promoter FY*02N.01-67c SNP".  Whatever that is.  The report seems very comprehensive with lots of information, including references.

Scott

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Thanks for that SMILLER.

The bit about the Duffy null promoter means that, although your patient has the FYB gene, the Fy(b) antigen will not be expressed on his red cells, because the GATA-1 mutation, present in a homozygous state, prevents the Fyb antigen from being expressed on the red cells - but only the red cells.  It will be expressed on other tissues throughout the body, and so this individual should not make an anti-Fy3, even though he is phenotypically Fy(a-b-) as far as red cell grouping is concerned.

NICE CASE!

 

The Fy(a-b-) phenotype in the Black Populations.pptx

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Interesting.  One question Malcolm, up until reading this report from our reference lab (most of which could be written in Greek and I would not understand it less) I had never heard of the DAU partials. 

I saw in one paper that the DAU-0 is thought to be the "primordial" example of this particular clade (if you want to call it that), and that DAU-1 through 5 are further variants on that.  This seems to go against the current distribution of the various DAUs (D - African Observed), where DAU-0 is found in Europeans, and all of the others are found in Africans.  Would this mean that the DAUs started in Europe and then somehow spread to Africa where they further differentiated?  It seem backwards somehow.

Thanks, Scott

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I thoroughly agree!

I read a paper on the subject once (Wagner FF, Ladewig B, Angert KS, Heymann GA, Eicher NI, Flegel WA.  The DAU allele cluster of the RHD gene.  Blood 2002; 100: 306-311, doi: 10.1182/blood-2002-01-0320) that purported to explain it all, but I warn you, it took me about 5 days to read, nearly boiled my brain, and I STILL don't understand it!  Mind you, that says more about my ability to digest the paper, rather than the way the authors explained the subject!!!!!!!!!!

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  • 2 weeks later...

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