Tabbie

Thanks for clearing that up.  Just a couple of things though.
Unless you can get your hands on some incredibly rare C Negative, Cw Positive red cells (they do exist, but they really are incredibly rare), you will not be able to tell if an anti-Cw is underlying an anti-C, and you wouldn't want to waste such precious cells on just proving that; you would want to preserve them for when you REALLY need to know for clinical reasons.
Cw is not a weak expression of the C antigen.  The "w" comes about because the donor who stimulated the first known anti-Cw was named Willis.  In addition, the "RHCw"gene is not allelic to the "RHC" and "RHc" genes (I KNOW this is incorrect nomenclature by the way!), but is allelic to both "RHCx" and "MAR", and so this has nothing to do with the Ceppellini effect.

Well, first things first, we would not rule out all clinically insignificant antibodies.  Why would we do that, if we know before looking for them that they are no more than a nuisance?  What would be the point?  We would look to detect antibodies that react at 37oC, and are known to be clinically significant, on a regular basis.  In other words, we would not look for Lewis antibodies, even though there are incredibly rare examples of transfusion reactions due to Lewis antibodies in the literature.  Similarly, and for the same reason, we would not look for cold-reacting anti-M, anti-N, anti-A1, anti-P1, anti-Lua and anti-Cw.  We would just perform alloadsorptions and, as long as we do not detect any clinically significant alloantibodies, we would give Rh and K-matched red cells, often by "immediate spin" cross-match, or, if there is a "cold" present, IAT cross-match against the adsorbed plasma.

Your a star Malcolm as ever complex but clear and reference to the GATA-1 gene to compare scenarios, putting it into perspective.
Much appreciated 

Not quite Tabbie - although it is difficult to explain - but I will do my best (but the explanation may not be perfect).
Rhnull individuals are incredibly rare throughout the world, and I really mean INCREDIBLY rare.  I have worked most (although not all) of my professional life in Blood Group Serology (partly at the International Blood Group Reference Laboratory, and partly at NHSBT-Tooting RCI Laboratory).  Because of the fact that the IBGRL is a World Health Organisation (international) establishment, they got/get samples of rare blood from all around the world.  Because NHSBT-Tooting RCI Laboratory covers hospitals that have an incredible mix of patient ethnicity, we also used to get a lot of VERY rare antibodies/antigens.  I think that I can say that, in 43 years in this environment, I have only seen two, maybe three families that included Rhnull individuals; that is how rare they are.
These individuals can (and do) make an antibody named anti-Rh29.  This antibody, in essence, reacts with all red cells apart from those of other individuals who have the Rhnull phenotype.  On the other hand, some individuals who have warm auto-immune haemolytic anaemia make an antibody that is very similar, if not (to all intents and purposes) identical to anti-Rh29.
Similarly, D--/D--, D../D.., D--/D.., D--/Rhnull and D../Rhnull individuals can make antibodies that look like a combination of anti-C, anti-c, anti-E and anti-e that cannot be separated (it is, needless to say, a bit - a lot - more complicated than that).  This antibody is termed anti-Rh17.  This antibody is, once again, not straightforward (as you might expect by now!).  This antibody is THE single most common specificity found in cases of WAIHA.  HOWEVER, just in case you thought things were getting easier, they are not!  The auto-anti-Rh17 you find in individuals with warm AIHA often (more often than not actually), reacts more readily with, for example E Positive red cells (or e Positive red cells, C Positive red cells or c Positive red cells) than with E Negative red cells (or e Negative red cells, C Negative red cells or c Negative red cells), irrespective of the fact that the patient is E Positive (e Positive, C Positive or c Positive).  You can tell that it is NOT anti-E (or any of the other specificities) by the fact that the antibody can be adsorbed out by E Negative red cells (it make take more adsorptions than with E Positive red cells, but you can still do it) - and, again, the same applies for other mimicking red cell antibodies.
These days, with the ability to use monoclonal Rh grouping antibodies, it is normally quite easy to tell if the antibody  is an auto- or an allo-antibody, even if the red cells are DAT Positive, because it is (usually) quite easy to sort out the patient's own Rh type.  As a result, it is VERY rare that an RCI Laboratory would bother to do too much work on it - basically, it would be a waste of time, reagents and money.
Turning to your other question, concerning how the genotype can be different from the phenotype, this situation is surprisingly much more common than you make think.
Some 68% of Black individuals are (phenotypically) Fy(a-b-), and yet, genotypically, most of these individuals are FYB/FYB, which begs the question, why are the red cells not typing as Fy(a-b+)?  Well, the answer is that there is another gene, called the GATA-1 gene that has to be present (and present in an "unmutated" form) for the antigen to be expressed on the red cell.  A large percentage of Black individuals have a mutation (and mostly as a homozygous gene mutation) that prevents the expression of the Duffy antigens on red cells, even though the blood group antigen genes are present on the chromosomes (chromosome 1 in this case, as it happens).  This is by no way the only time that a genotype does not match the phenotype.  There are loads of others (for example, Partial D Type III has gene mutations that can allow the individual to make a genuine allo-anti-D - and pretty strong anti-D at that - but, phenotypically, the person is a straightforward D Positive individual).  The same applies with e variant mutations, such as hrB and hrS.
I hope all this helps, but, if not, get back to me (or others on this wonderful site).

The anti-D produced by a D Variant individual is slightly different to the anti-D produced by a true D Negative individual.  For example, if we look at the attached cartoon of the amino acid residues in Partial DVI Type 1 (based on a slide by Dr Geoff Daniels), the black circles represent amino acids encoded by exons derived from RHD genes, whilst the gold circles represent amino acids encoded by exons derived from RHCE genes (see also the exon map at the bottom of the cartoon)  However, the anti-D produced by such an individual will only be produced against the D epitopes missing from the Partial D Type 1 molecule, rather than the entire D molecule.  Such an "anti-D" would, of course, react with a "normal" D antigen, as the epitopes missing from the Partial DVI Type 1 would be present in the molecule of the "normal" D (and would, of course, also react with any other D Variant that expresses these epitopes).  This can also be proved by the fact that the "anti-D" produced by one individual with the Partial DVI Type 1 variant will not react with the red cells of another individual with exactly the same Partial DVI Type 1 variant.
The same applies with all other variants (i.e. the "anti-D" produced will only react against the D epitopes "missing" from the molecule).  What must also be remembered is that changes in amino acid residues may also affect the quaternary structure of the molecule as a whole, particularly if, for example, an amino acid with an acidic side chain, replaces one that has a basic or neutral side chain (or vice versa), which could have the effect of causing the entire molecule to distort, meaning that such an individual can make an "anti-D" against D epitopes that are apparently present, but are, in fact missing, because of the affect of this distortion.
As a result of all this, the "anti-D" produced is a true allo-antibody, rather than an auto-antibody, and this would explain why the DAT would be negative, as would the "auto".
I hope this rather complicated explanation helps a little bit!
Partial DVI Type 1.pptx

I work in a small lab we just don't get the experience of the unusual. I am trying to learn more by posting hypothetical case studies as I cant post real ones.
Thanks
 

NO!  Under no circumstances, even if the DAT was negative with anti-C3d (as it usually is in cases of PCH).  The titre (Tabbie, you are in the UK, so spell it the correct UK way!  ) is of no relevance whatsoever, and knowing it would make no difference to the way the patient is treated.

the same as you would for any other antibody
But you need to make sure that if there is an anti-Lea or -Leb present that it is reacting strictly at 37°C.  Otherwise no clinical relevance at all

If the genotype was done with full sequencing and the phenotype was tested with various clones and all of that said negative, how did the paper come to the conclusion that this was an auto anti-C rather than an allo-anti-C?

I like things to be right keep up the good work of correcting and educating 😀
 

Patient phenotype is Fya + Fyb+
I just had not seen a Gata mutation result before had read about it. Thought it may be an additional molecular phenotype request but it was included in the panel reported

and often only with enzyme treated cells tested in an IAT....
 

Yes.  As anti-Jka is renowned for being labile both in vitro and in vivo, if you "catch" an anti-Jka when it is "on the decline" from reacting by IAT and with "enzyme only", you will quite often see an allo-anti-Jka reacting only with enzyme-treated red cells - which is part of the reason why they are just SO dangerous, as we would not detect them in an IAT antibody screen.

Homozygous unless demonstrating anti-D (heterozygous C, E).
With anti-c or anti-e, uncomfortable with ruling out E, c on heterozygous cells.  Would prefer to type the patient (if possible) and give phenotypically similar.

3 homozygous cells, unless we are ruling out C or E in the presence of anti-D. In that case we use 3 heterozygous rule outs.

One way of ruling IN anti-P1 is to incubate the panel at room temperature and below, in particular with papain-treated red cells.  This will lead to much stronger reactions if the antibody is an anti-P1.
Another is to inhibit the anti-P1 with either pigeon egg white (difficult to come by) or pigeon guano (difficult to avoid - particularly in Trafalgar Square!).

If you get your reverse grouping cells from NHSBT, they are always a pool of rr donors, and so will always express the c antigen.

The reverse grouping red cells in the UK often react with an anti-c.
I would be happy (on the evidence you give) to transfuse c-, E-, K- cross-match compatible blood.
As you KNOW that the patient is group A, I would ignore the bit about giving group O blood, which is totally over the top.
 

I can see no reason why you should not transfused D Positive red cells.

Well, the thing is that the FcY receptors on the immune system leukocytes are few and far between, so such antibodies are often clinically insignificant.  As a result polyspecific (broad spectrum) and monospecific anti-IgG reagents often do not detect such antibodies (or do so ineffectively) and so these are often (deliberately) not detected.  In addition, IgG2 and IgG4 are not good at initiating the complement system (IgG4 doesn't at all).  Lastly, of course, some of these antibodies can be IgA and, again, they are, at most, of doubtful clinical significance.

Unfortunately, what you say is far from "universal".  Certainly, it is unusual to see an antibody directed against a low prevalence antigen causing either HDFN or an HTR, but it is by no means unknown.  For example, anti-Bea has caused very severe HDFN, and anti-Wra caused a fatal HTR only a couple of years back in the UK.
In terms of the 901 series (and, come to that, anti-U of the MNS Blood Group System) it is possible that it is to do with the IgG subclass, but it is more likely to do with them being (occasionally) IgG2 and/or IgG4, but, as far as I know, this remains a theory, rather than having been proven.

Just for info - CellStab is not a LISS solution and Diluent 2 is - but you can't store red cells in dil 2 because they will haemolyse after a while

History is part of the workup--it doesn't matter if the info is from my own system or another hospital's--I would try to get those concession/declaration forms signed after a consult with the attending.
Scott

Yes, frequency, incidence and prevalence are all interchangeable with either "high" or "low" before any of them.  For some reason (I know not why), low prevalence has suddenly become the "word of the day", but there is no particular reason for this (as far as I know).
Those low prevalence antigens within the 700 series, and, come to that, the high prevalence antigens within the 901 series, are, as you say, placed there as they do not belong to any known blood group system.  However, do not run away with the idea that all low prevalence antigens are in the 700 series, and all high prevalence antigens are in the 901 series.
The antigen KREP, of the Diego Blood Group System has only ever been reported in one Polish individual and one Slovakian individual, and yet it is not in the 700 Series of antigens.
Conversely, and as far as I know, DOLG of the Dombrock Blood Group System has only been found to be negative in one Sri Lankan woman, and yet is not in the 901 Series of antigens.
This is because, in each case, the chromosome and the particular loci have been identified, and they are mapped to known areas of the genes which encode each of these antigens. 

We used to do eluates but with the infrequency of need and competency challenges we decided to send to our reference lab. We request eluates on patients who need a transfusion (or investigating a TRRX) and are DAT + and who have been transfused within the past 14 days to rule out newly forming antibodies that could be completely absorbed onto the donor RBCs and may not be found in the plasma.  Our reference lab has recently changed from 14 to 21 days post transfusion for eluate testing but we have not yet changed our rule.  I believe the thought process behind this is that after 14 (or 21) days the newly formed antibody has had sufficient time to spill over into the plasma and can be identified in the ABSC/ABID.  On patients that are transfused frequently we sometimes opt to give phenotypically similar blood for transfusion instead of sending out for an eluate with each transfusion event as this is time consuming and expensive.