Mrs X Para 2+1 with dichorionic diamniotic twins.

Anti-D+G present

Anti-D quantitation levels at 13+2 and 29+3 weeks were 21IU/mL-1 and 330IU/mL-1 respectively.

Mum O RhD Positive rr, Dad A Rh D Positive R2Ro

Twin 1: A RhD Positive DAT 4+, did not go over 1.5MoMs on middle cerebral artery Doppler peak systolic velocity surveillance and did NOT require IUT. Postnatally only required top up Tx’s

Twin 2: O RhD Positive R2r DAT 4+. required three intrauterine transfusions. Postnatally required Exchange Tx, IVIg and phototx and serial top-ups

Although both twins in this case were RhD positive only one was severely affected.

What are the possible reasons / theories to explain this disparity?

According to Mollison there are 3 circumstances the fetus may be unaffected or only mildly affected despite a strong positive result in a cellular bioassay. These are:

1. Fetus Rh D Negative

2. Presence of Fc receptor blocking antibodies

3. Diminished transport of maternal IgG to the fetus

Are there any other suggestions theories or advice?

I would be interested to know the full Rh types of the twins.

 

Was twin 1 R_or and twin 2 R₂r?

 

The reason I ask is that, amongst the common D+ types, the number of D antigen sites per red cell is highest when the DcE haplotype is present (even higher when the type is R₂R₂ of course), and, therefore, such red cells are more likely to be sensitised by an anti-D.

 

Another thing that springs to mind (as a possibility) is that the mother's anti-D, being polyclonal, rather than monoclonal, will be a "soup" of antibodies directed against all sorts of epitopes of the D antigen, and it may just be that the D of the second twin expressed more of the epitopes against which the mother had made anti-D, than the D of twin 1.

 

It may be, of course, that twin 1 has a D antigen that, whilst easy to detect with your routine anti-D typing reagents, is actually a Weak or Partial D, and may have a lower number of D antigen sites per red cell than twin 2.

 

I must admit though - I am struggling with this one!!!!!!!!!!!!

I wonder if maternal Anti-A has somewhat of a protective influence on twin 1 (Group A) and not on twin 2 (Group O).  If I recall correctly, this was the assumption that led to the development of Rh immunoglobulin.  Baby's born to mothes with ABO incompatabilities generally demonstrated less severe Rh(D) HDN than those that were ABO compatible. 

 

Just my 2 cents.

I see from where you are coming MikeB, but that has more to do with whether or not the mother is likely to make the anti-D in the first place.  For example, if the mother is group O, D Negative primigravida, and she is carrying a group A, D Positve foetus, and there is a feto-maternal haemorrhage, the mother's anti-A will give her some defence against making an anti-D, as the foetal group A red cells will be removed from the maternal circulation before the mother is stimulated to make anti-D.  If, however, the foetus is also group O, then the D Positive foetal red cells will survive normally in the maternal circulation - certainly long enough to stimulate an anti-D.  Hopefully, I have added a slide showing what I mean.Protection.ppt

 

As far as I am aware, once the mother has made an anti-D, the foetal ABO group gives no protection whatsoever.

Edited November 26, 201410 yr by Malcolm Needs

No possibility of twin to twin transfusion and increasing the titres in one baby and lessening them in the other?

Wouldn't have thought so, as the maternal anti-D would be the same in each twin.

 

The other thing is that, if there was a twin to twin transfusion, you would expect both twins to have mixed-field with anti-A in this case.

I'm going with the R0 being a Dweak or a partial D that nonetheless has reacted normally with the reagents that were used. - provided of course that the baby was a group Ror as well. 

Incidentally, I presume the mum is ONeg rr, and not Opos rr as in (I hope) the typo above.......

 

I this dad the father of her previous babies?  I'm just wondering about the anti-G.......

Would be interesting to see what was eluted from the babies red cells. Could anti-A bound to twin 1 have blocked binding of some of anti-D and anti-G? Does not sound very lkely, must admit!

Apologies Mum is O RhD Negative (that was a typo!!)
 
Twin 1 = Ror
Twin 2= R2r
 
Twin-Twin transfusion usually not possible with dichorionic diamnionotic, primarily only seen with monochorionic. 
 
Just to note Twin 2 was grouped pre 1st IUT at 27 weeks when the Anti-D levels were not near as high as when Twin 1 was grouped in the neonatal period at 34+3 weeks gestation, Twin 1 Grouped as A but weak reactions against the anti-D reagents, we assumed that this could be the blocking effect- where high anti-D levels result in blocking of D antigen sites resulting in false negative or weakened RhD group. Elusion demonstrated that it was Rh D+ve
IgG and IgM were coating the baby red cells , DCT strong positive (4+), IgG 4+ IgM 2+ ? Origin of IgM.

On RhD antigen density Issit & Anstee quote the following:
R2r has 14,000 to 16,500 D antigen sites
Ror has 12,000 to 20,000 D antigen sites

Initially I assumed it may have been due to the fact the twin was Ror until I discovered the no of antigen types in Ror and R2r

 

 

Well, it could easily have been blocking, but it could just as easily have been that the D antigen is a genuine Weak D or Partial D.  The fact that you could elute off anti-D just confirms the presence of some sort of D antigen - not the presence of the "wild-type" or normal D antigen.  After all, adsorption and elution (together, of course, with molecular techniques) is how D_el is demonstrated.

 

I wonder where the IgM came from too, unless there was a slight (minute) tear in the placenta, which allowed IgM across.  If this were so, it may also explain why the twin was more affected, as such tear would also allow more IgG to get through.

Still need to know what antibodies were eluted from the red cells of both babies. Also, were the monospecific DAT results the same in both twins? Starting to seem possible that twin 1 is a 'weak/variant D'. We've certainly seen 'weak/variant D' newborns (where mother has high level of immune anti-D) with strong positive DAT results, and elutable anti-D, who have supprised us by being completely unaffected by HDFN.

For the IgM - I wonder what type of Coombs reagent you were using to check that?  Heavy chain or light chain?  Could just be cross-reactivity

We wrote this case report up and it got published in Transfusion Medicine.  I can email the paper if anyone is interested.