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Anti-D in O positive patient, DAT+, no RhIg given


L.C.H.

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Since PathLabTalk just asked folks to please participate by making a post, I'll offer up our conundrum of the day - we haven't yet done much workup:  

Young healthy woman had early pregnancy loss last year, she typed twice as O pos, no antibodies, did not get any products. We did not have to do a weak D on her.

Now in early pregnancy again; early this month she showed O pos, antibody screen pos, antibody not ID'ed, positive DAT, no lab evidence of lysis.  

We asked for more tubes but they sent only one, now several weeks later. Again O pos, antibody detected, though decreased in intensity - and now is ID'ed as anti-D

Both times the antibody has been stronger than would be expected for RhIg, and anyhow I can find no instance of her having been given RhIg. 

In Feb she had strep throat but she was treated, so I don't think it is a post-strep autoimmune phenomenon (plus I dont think that usually manifests against RBC antigens?)

Anyone seen anything like this? We are going to again ask for more tubes so we can send her to reference center.  

I will post follow-up as we work this out.

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Does the patient have ITP? Is it possible that she is receiving WinRHO (same as RHIG) for ITP? Does she have a low platelet count. I haven't seen this situation in several years but there was a time when patients with ITP who were rh pos would be treated with WinRHO (as long as they had their spleen). It would present as this very scenario you are describing.

Another possibility is anti-Lw?

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Here are some thoughts 

1. Prophylatic anti-D given after pregnacy loss despite her D pos type and not communicated further (but sounds like the event is too old to support this option right?)

2. Can be an anti-LW instead which looks like auto anti-D (reacting stronger with D pos cells)

3. Other blood derived product given (e.g. IVIG) containing anti-D but the reaction strentgh does not support this hypothesis

4. D variants alloimmunized during first pregnancy with D pos fetus

 

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Auto-anti-D is more common that a lot of people think, but I am NOT saying that is what this is - just that it may be.

It could also be that the D antigen of the individual is a Partial D Type, such as Partial D Type III, that would react like a "normal D" (in fact, it would have slightly elevated expression of the D antigen), but who could easily produce an allo-anti-D (and there could also be an auto-antibody present, accounting for the positive DAT).

In addition, particularly as the DAT is positive, the actual specificity of the antibody in the individual's plasma/serum could be an auto-anti-LW, that would mimic an anti-D.  This could be resolved by testing the antibody against a few group O, D Negative cord red cells, which would give fairly strong reactivity.

In any case, I would send a sample to a Reference Laboratory to ascertain the true specificity of the antibody, but also, as Ensis01 says, for molecular characterisation of the RHD gene (and do not forget to tell them the ethnic background of the individual, as this will make their lives so much easier).

Finally (for now, unless anything else springs to mind), please would you keep us informed of the outcome and results?  THANK YOU; an interesting case.

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I also should get up earlier to contribute! thank you all for the suggestions!

In response to some of the ideas -  her pregnancy loss end of last year and surrounding OB care was entirely through my institution, and I know we didnt give her any RhIg of any sort. Could find no evidence of ITP (handful of CBCs over months have been dead normal), no evidence of any underlying autoimmune disorder. No evidence of getting IVIG or any other antibody-based treatment. The only possible autoimmune trigger I recognized was the strep throat, but that's a long shot and anyhow she was promptly treated.  And we don't use gel.

Overnight we came up with some of the same ideas as y'all - warm auto with anti-D specificity, an anti-LW, or a D antigen variant. 

Just hearing from the manager we ran her against some O negative cord cells this morning; does not look like an anti-LW. We are opting to use what is left of the sample to send to reference for the D chip. I'll definitely update once we have more info!

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  • 2 weeks later...

OK, follow-up as promised with results of the D chip - and I have some reading up to do on these.

Overall predicted RhD phenotype: D+ (weak partial)

Alleles:

- RHD*weak partial 4.0  encodes p.201Arg and p.223Val

- Hybrid RHD*D111a-CE(4-7)-D does not encode D but encodes partial C as part of r'S haplotype

 

The report includes a reference: "Experience with RHD*weak D type 4.0 in the USA," Blood Transfusion 2018:6: 1-3. 

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

 

- RHD*weak partial 4.0  encodes p.201Arg and p.223Val

- Hybrid RHD*D111a-CE(4-7)-D does not encode D but encodes partial C as part of r'S haplotype

 

I was wondering why does  she express D pos, if the allele can not encode D?

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

OK, follow-up as promised with results of the D chip - and I have some reading up to do on these.

Overall predicted RhD phenotype: D+ (weak partial)

Alleles:

- RHD*weak partial 4.0  encodes p.201Arg and p.223Val

- Hybrid RHD*D111a-CE(4-7)-D does not encode D but encodes partial C as part of r'S haplotype

 

The report includes a reference: "Experience with RHD*weak D type 4.0 in the USA," Blood Transfusion 2018:6: 1-3. 

Presumably predicted to be V-VS+ ? Might want to check on the hrB status, too.

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4 hours ago, yan xia said:

I was wondering why does  she express D pos, if the allele can not encode D?

yan xia, there are two mutations present.

The first, RHD 4.0/RHD DAR3.1.  This will lead to the expression of a Partial/Weak D.

image.thumb.png.c6b7bd19d015376bdc1eb4b005fc42aa.png

The second mutation is a hybrid of the RHD and RHCE gene, with exons four to seven of the RHD gene being replaced, or substituted, by exons four to seven of the RHCE gene.

image.thumb.png.7b50382043b1e74937db9626bf4b4e3f.png

I hope this helps a little.

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