Malcolm Needs

Welcome psykobillys.

This PowerPoint Lecture gives some idea about how we approach things in the UK. It may well be different in other countries. In Depth Lecture on Alloimmune Haemolytic Disease of the Foetus and Newborn HDFN.pptx

The UK has (I was one of the co-authors). Guideline for blood grouping and red cell antibody testing in pregnancy. White, J, Qureshi, H, Massey, E, Needs, M, Byrne, G, Daniels, G, Allard S, British Committee for Standards in Haematology. Transfusion Medicine, 2016, 26, 246–263. doi: 10.1111/tme.12299.

Well, the first thing to say is that red cells CANNOT be either homozygous or heterozygous (or, come to that, hemizygous). These terms apply ONLY to genes, and red cells do not contain a nucleus. The antigens can only be described as, at best, "homozygous", "heterozygous" or "hemizygous" expression, or, alternatively, "double" or "single dose" expression. Then, it HAS to be accepted that, unless the maternal antibody is an autoantibody, it must be an alloantibody (or, possibly, an isoantibody), which means that to mimic the state of the foetal red cells, the red cells used to titrate the antibody MUST have a "single dose" expression. However, that in itself presupposes that the foetal red cell antigens are all expressed at the same time, which we know is untrue (just look at the A, B and H antigens as an obvious example, but also the Kell antigens that are expressed much earlier than are the Rh antigens) or are ONLY expressed on foetal red cells, as opposed to other tissues (such as on the placental cells, which have, in some cases, been proved to adsorb the maternal antibodies). Then, there is the fact that not all antibodies can be detected by all techniques. This is why Reference Laboratories SHOULD have more than one technology available (and their workers should be provably competent in these techniques. However, even then, not all techniques can predict the severity or otherwise of HDFN. For example, antibodies within the Indian Blood Group System always show that they can cause severe HDFN by certain techniques, such as MMA, but they don't! There is also the fact that the immunoglobulins may be IgM, IgA, IgG1, IgG2, IgG3 and IgG4 (to mention just a few), and I have yet to come across, or read about, an IgG4 immunoglobulin causing HDFN. So, my answer is that there is a HUGE amount of knowledge known about the various antibody specificities, their titres, the expression of their cognate antigen, etc, etc, that there CANNOT be a single answer to your excellent question, but that the best thing that can be done is to read around the subject - and read around the subject from every source available - not just from a single country. OKAY THEN, RIP ME APART!!!!!!!!!!!

Welcome julie anderson.

Welcome Jessica Reed.

Welcome scyteklabo.

Welcome MichelleM.

Welcome TattedTech.

Welcome kmiller,

This may or may not help. Clinical Aspects of Transfusion Reactions.pptx

Welcome jamesbarry.

Welcome Lab202002.

Welcome Caitlin.

Another idea. Not mine, but I wish it was!

Welcome My Hematology.

Welcome Misty Biggs.

As someone who was the lead in the Red Cell Immunohaematology Laboratory in Tooting, London for well over a decade, I would say that it is a mixture of the two, but about 75% science.

Welcome Jen Sukke.

Welcome Hanady Samaha.

Okay, so as long as the said antibody is tested each and every time, to ensure that the antibody specificity has not "broadened", but also that the thermal amplitude has not changed, so that, "this time" it may be a clinically significant "cold-reacting antibody", rather than a clinically insignificant "cold reacting antibody". Sadly, it is not even THAT simple (if only), but it depends upon the specificity of the antibody and, to a certain extent, the ethnicity of the patient. "Cold-reacting" anti-M, for example, is known to be much more clinically significant in people from the Far East (particularly Japan) than in any other ethnic group, as far as I know. However, if you take the "antibody" out of the computer system, so that it no longer flags, there is the very real possibility that a formally clinically insignificant "cold-reacting antibody", that has developed into a clinically significant "cold-reacting antibody" may be ignored - not "not detected" (far from it) but ignored, because "it was okay last time"! All that having been said, I have NEVER understood why time and money is spent on determining the specificity of a genuine cold-reacting antibody, rather than just determining the thermal amplitude, to determine the clinical significance, and bothering to provide antigen negative blood, when there is zero chance of a haemolytic transfusion reaction!

I agree Neil. I hope the "deactivation" does not involve the denaturation of IgM molecules by, for example, dithiothreitol. This would be a great way to miss most examples of anti-Vel - a VERY clinically significant antibody!

Have you thought about training porters? I know that sounds a bit "Left field", but it worked for us in the UK in a couple of hospitals where I worked. You have to be pretty strict, but it does mean that nursing and lab staff can get on with other things.

The first, and most important, thing to remember is that ABO antigens are "carbohydrate-based" and are not, therefore, direct gene products (not that any antigens are, as every one of them undergo post-translational changes). The direct gene products are, of course, the A, B and H transferase enzymes. At birth, it is incredibly rare for the enzymes to be "working" at its optimum/maximum, so that it is rare for the ABO antigens to be expressed maximally (or anything like) at birth. I am certain that you know all this already, so that I am probably "teaching my Grandmother to suck eggs", as the old (and in this case, almost certainly, insulting) adage goes. As a result of the above, however, unless you can perform A, B and H typing by molecular techniques (NOT to be recommended - see Geoff Daniels book, Human Blood Groups), you either have to decide to ignore all serological cord ABO types, and call all of them O, or, you have to use serological methods that will enhance the antibody/antigen reactions. Herein, there are inherent problems. Firstly, whatever enhancement you use, you MUST use a suitable negative control. It is fine (in my opinion) to vary the incubation temperature from RT to 4oC, but, to so do, it is very necessary to use another cord blood from a known group O cord sample (i.e. where both parents are KNOWN to be group O themselves, and so an A or B subtype in terms of the control is not a problem). Similarly, the same can be said for enzyme-treating the baby's red cells, as long as the control cells are also treated in EXACTLY the same way with the proteolytic enzymes. Finally (at least for now!!!!!!!), it should be remembered that we routinely use monoclonal ABO antibodies these days. These are extremely avid, which is fantastic, but are also VERY specific, which can be a drawback. By this I mean that the old polyclonal human-derived ABO antibodies we used to use (when I was middle-aged, and Karl Landsteiner was a young boy) had the single (and probably only) advantage that they were not quite so specific, and would, therefore, detect ALL (or most) ABO antigens, including those that the monoclonal antibodies would not necessarily detect. For an explanation of this, there was a recent paper in Vox Sanguinis (Cripps K, Mullanfiroze K, Hill A, Moss R, Kricke S. Prevalence of adsorbed A antigen onto donor-derived group O red cells in children following stem cell transplantation: A single-centre evaluation. Vox Sang 2023; 118: 153-159. DOI: 10.1111/vox.13386) talking about the A antigen being adsorbed onto the surface of group O red cells in vivo. One of the references they use is the first peer reviewed paper that I ever wrote, concerning A and/or B substance being adsorbed onto the surface of donor-derived red cells in vivo. What I failed to say in this paper was that this phenomenon was far easier to detect with polyclonal ABO reagents than monoclonal ABO reagents (36 years, and I still regret this omission!). Anyway, IF I HAVEN'T SENT YOU TO SLEEP YET, my point is that, as long as you use suitable controls, particularly NEGATIVE controls, there is no reason why you should not use any modification to any technique (GIVEN THAT IT IS IN YOUR SOP, with all the qualifications given above), and, even then, if you feel it safer, GIVE GROUP O BLOOD.

Welcome tnbloodbank.