Can patients with Weak D antigen develop anti-D?

[YorkshireExile]

Our hospital policy is not to give an anti-D injection to our antenatal patients who have a weak D antigen. This is based on the RCOG guidelines of March 2011 which specifically state "Patients with a weak D antigen DO NOT develop anti-D". Is this correct? I`m sure I`ve read literature in the past where these patients can, albeit rarely, develop anti-D.

We do not specifically test our antenatal patients for the weak D antigen, but the fact that we use the Diamed (Biorad) gel ABO/Rh+Reverse group cards means we can see clearly when there is a +2 agglutination or less with the D antigen, so we feel obliged to report the group as Weak D positive.

Does anyone routinely give an anti-D injection to these weak D patients?

[khalidm3]

Term Weak D is applied to AHG test (Du), not to direct Rh test. If the reaction in direct test is less than +2 by manual or less than +3 by DiaMed Cards, we should further evaluate/trace that it is not from FMH or Rh in compatible transfusion.

Week D test is not required to perform for patients other than new born. So if a pregnant female is direct Rh negative, and her husband/baby is Rh positive or week positive, she is a candidate for RhoGm.

We perform week D (AHG) for our all our patients and donors and inform them their actual Rh status, Rh Negative, Rh Week Positive or Rh Positive accordingly.

[Malcolm Needs ☆]

With the advent of molecular testing, the area between Weak and Partial D has become more than a little muddied.

Originally, it was thought that, if the amino acid substitution was within the cytosol or intramembranous, the resultant D antigen would be Weak, but if the amino acid substitution was extracellular, the resultant D antigen would be Partial.

This has proved not to be so, as some of the individuals with "Weak D" ("proven" by molecular testing) have produced alloanti-D.

This is why the term "D variant" is far better to describe all such substitutions, rather than the two, somewhat nebulous, terms above.

It is safe to say that the three most common forms of Weak D, Weak D 1, 2 and 3, only form alloanti-D on very, very rare occasions (and, even then, the anti-D formed tends to be extremely weak), but anything "weaker" than these should most definitely be regarded as capable of forming alloanti-D, and treated as such.

[YorkshireExile]

Thanks for the reply Malcolm.

So is the RCOG statement of March 2011 "Women who have a weak expression of the RhD blood group do not form anti-D and therefore do not require prophylaxis" correct or incorrect?

In a routine hospital lab situation I would never know if my weak reactions were due to a weak D or a partial D. All I can report is the phrase they are familiar with i.e Weak D. So should I be advising my doctors to give these patients an anti-D injection during their pregnancy? Or should I just settle for an easy life and agree with the RCOG and our current policy

[Malcolm Needs ☆]

Thanks for the reply Malcolm.

So is the RCOG statement of March 2011 "Women who have a weak expression of the RhD blood group do not form anti-D and therefore do not require prophylaxis" correct or incorrect?

In a routine hospital lab situation I would never know if my weak reactions were due to a weak D or a partial D. All I can report is the phrase they are familiar with i.e Weak D. So should I be advising my doctors to give these patients an anti-D injection during their pregnancy? Or should I just settle for an easy life and agree with the RCOG and our current policy

Well, strictly speaking, the statement is incorrect, BUT, finding a Weak D that is weaker than Types 1, 2 and 3 would be rare, and you would certainly detect almost all of these with your routine anti-D reagents (by that, I mean that they would give weird, unexpected results, and these should always be checked by a Reference Laboratory), so, I think that pragmatism is the order of the day in this case and I would agree with you that you go for the easy life!

:boogie::boogie:

[YorkshireExile]

Well, strictly speaking, the statement is incorrect, BUT, finding a Weak D that is weaker than Types 1, 2 and 3 would be rare, and you would certainly detect almost all of these with your routine anti-D reagents (by that, I mean that they would give weird, unexpected results, and these should always be checked by a Reference Laboratory), so, I think that pragmatism is the order of the day in this case and I would agree with you that you go for the easy life!

Presumably, if any of my maternal "Weak D" patients required a transfusion I should still try to give them RhD negative units just to be on the safe side?

[Malcolm Needs ☆]

I wouldn't; not if they are strong enough "Weak D"s to react with both of your anti-D reagents.

[galvania]

Although I agree with Malcolm, you certainly need to check your local (national) guidelines and act accordingly. In Switzerland, since last year, any female of childbearing age (defined as under 50) who shows a result with anti-D that is not completely positive or negative in direct testing has to be sent for molecular biology. All D weaks other than types 1, 2 or 3 have to be treated as D negative if patients and , if pregnant, ARE given anti-D prophylaxis accordingly. They are also transfused with D neg blood. I'm not sure what the regulations in other countries are.

[Yanxia]

Execuse me , what is weaker than weak D type 1,2,3? How can I know they are weaker than those type? Thanks in advance!

[Malcolm Needs ☆]

Basically, Weak D Types 1 to 3 will usually give obvious agglutination with the modern monoclonal anti-D reagents (although some Weak D Type 2 individuals do have very weak D antigens) of, about, 2+ or stronger.

Any reactions weaker than that (particularly if one anti-D shows agglutination, and the other doesn't) should alert you to the fact that you are dealing with an individual who has either a Partial D, or a Weak D that is Type 4 or above (there are something like 70 now, if you include the subtypes)!

[Liz]

Thank you for your explanation Malcolm; do they know how the intracellular amino acid substitution can stimulate the immune system and the formation of anti-D? Is it because after hemolysis of senescent RBCs the internal "weird” D is exposed? Regarding patient management, I agree with Anna on this one. I prefer to err on the safe side.

[Malcolm Needs ☆]

Thank you for your explanation Malcolm; do they know how the intracellular amino acid substitution can stimulate the immune system and the formation of anti-D? Is it because after hemolysis of senescent RBCs the internal "weird” D is exposed? Regarding patient management, I agree with Anna on this one. I prefer to err on the safe side.

No, it is more to do with what amino acid residue is substituted for the original amino acid residue. If, for example, aspartic acid (which is a polar, uncharged amino acid) is substituted for argenine (which is a polar, positively charged amino acid), the difference in charge can alter the quarternary structure of the entire RhD molecule, including the external structure, and expose different amino acid residues and the molecule will be a different shape to the "wild-type" RhD molecule. Therefore, the immune system will "recognise" the "wild-type" RhD molecule as "foreign" and may, therefore, produce an alloanti-D.

It's all a bit complicated for a simple blood group serologist like me, who has never had any formal training in molecular techniques!!!!!!!!!!

:confuse::confuse:

[Yanxia]

Thank you for your explanation Malcolm; do they know how the intracellular amino acid substitution can stimulate the immune system and the formation of anti-D? Is it because after hemolysis of senescent RBCs the internal "weird” D is exposed? Regarding patient management, I agree with Anna on this one. I prefer to err on the safe side.

I remember the intracellular amino acid substitution mostly produce weak D or Del. If my memory cheat me, please correct it.

[Malcolm Needs ☆]

No, you are quite correct Yanxia. Nevertheless, some of the "contortions" that the amino acid residue substitutions cause to the D protein can allow them to produce a genuine (although, usually weak) alloanti-D.

[Liz]

It makes sense, thank you Malcolm.

[Brenda K Hutson]

I have seen partial D patients make anti-D but they were primarily patients who typed as Rh Positive; then appeared to make Ant-D (so wondered if Auto-D or Anti-D due to partial type; but had partial D confirmed). But I think the possibility would be there for a Weak D reacting only at AHG, to make anti-D (though rare).

The decision about which types qualify for Rhogam, is an Institutional decision. I have seen different protocols. Where I am currently, we do not perform Weak D testing on pregnant women; only on babies. That is because we would give Rhogam even if they were Weak D positive; so why bother to find out if they are (though that sometimes comes back to bite you in that you get a strongly positive Fetal Screen Test on Weak D women). But in Institutions that prefer to "play the odds," they might say only Rh Negative women qualify for Rhogam; not Weak D (as you mentioned in your posting).

Brenda Hutson, CLS(ASCP)SBB