Malcolm Needs

No, I hadn't, but I am not surprised that ABO antigenicity is thought to make a difference.  ABO antigenicity makes a difference with several pathological conditions.

I've had a look at it, but not a detailed look.

I think I understand Dr Neil Blumberg's argument vis-a-vis ABO immune complexes being lethal, BUT, basically, I think here we are talking, largely, about giving blood to get people to the hospital before they die, and then giving them the best we can/idealised treatment, rather than trying to give them idealised treatment at the "roadside" (or wherever the life-threatening injury takes place), in order to keep them alive long enough to get to hospital; and there is a big difference between the two.  Certainly, it has been shown that there is a big difference between the way a blunt trauma injury is treated than a sharp trauma injury is treated and, as a consequence, the 1:1:1 red cell/plasma/platelet ratio (or near to that ratio) is not necessarily the best for all incidents.

To a certain extent, I am very glad that 1) I am not a clinician, and so the decision will never be mine (particularly as statistics is a branch of mathematics that is even worse than most other branches of mathematics in what I can either understand or do!), and 2) that I am retired.

The whole thing reminds me of the arguments concerning the use of clotted samples, which were used universally, when it was thought that detecting haemolysis and complement activation was essential, as opposed to the use of EDTA anti-coagulated samples.  There was a huge kick-back against the use of EDTA because antibodies may be missed, but, eventually, the statisticians got involved, and showed us we were talking nonsense, which then allowed us to introduce automation and, as a consequence, transfusion with minimal human intervention (hence fewer mistakes, particularly as machines do not get tired).  However, that does not mean that transfusions are without dangers - particularly in cases involving, for example, anti-Vel and anti-Jka.

It seems to me that, at the moment, "you pays yer money and you takes yer choice!".

As I say, I instinctively have sympathy for Dr Neil Blumberg's viewpoint, but I feel that we still need more evidence.  Meanwhile, I know for a fact that the HEMS in the UK are delivering more live patients to a hospital alive, using packed red cells and tranexamic acid, and these patients are surviving and staying in hospital for shorter periods, and using fewer blood components during their stay than before we used anything - when patients died on the spot.

I have no idea what is best, but there is no doubt that we are doing better than we were.  Dr Neil Blumberg would not have so many patients to determine his statistics (and he may well be correct - don't get me wrong) if it were not for the fact that many more patients are getting to the hospital alive these days.

I'll have to read it Scott.  It has largely passed me by.  It may have to be tomorrow now though.

Will do!

Sorry to take a bit of time answering Mabel.  We are having our place decorated, and are also having it valued by three different estate agents and, to cap it all, I am having my car repaired!  Never a dull moment!

As far as papers about anti-M in pregnancy are concerned, there are not many because, as Geoff Daniels writes, HDFN caused by anti-M is rare (and few people publish when an antibody is found not to be clinically significant, unless the antibody itself is rare, and not much is known about it), but Geoff does caution that HDFN, when caused by anti-M, can be quite severe., the papers he quotes are as follows:

Stone B, Marsh WL.  Haemolytic disease of the newborn caused by anti-M. Brit J Haematol 1959; 5: 344-347.

Macpherson CR, Zartman ER.  Anti-M antibody as a cause of intrauterine death.  A follow-up.  Am J CLin Path 1965; 43: 544-547.

Yoshida Y, Yoshida H, Tatsumi K, Asoh T, Hoshino T, Matsumoto H.  Successful antibody elimination in severe M-incompatible pregnancy.  New Eng J Med 1981; 305: 460-461.

Duguid JKM, Bromilow IM, Entwistle GD, Wilkinson R.  Haemolytic disease of the newborn due to anti-M.  Vox Sang 1995; 68: 195-196.

Furukawa K, Nakajima T, Kogure T, Yazaki K, Yoshida M, Fukaishi T, Ibuki Y, Igarashi M.  Example of a woman with multiple intrauterine deaths due to anti-M who delivered a live child after plasmapheresis.  Exp Clin Immunogenet 1993; 10: 161-167.

Kanra T, Yuce K, Ozcebe OI.  Hydrops fetalis and intrauterine deaths due to anti-M.  Acta Obstet Gynecol Scand 1996; 75: 415-417.

Hinchliffe RF, Nolan B, Vora AJ, Stamps R.  Neonatal pure red cell aplasia due to anti-M.  Arch Dis Child Fetal Neonatal Ed 2006; 91: F467-F468.

Wikman A, Edner A, Gryfelt G, Jonsson B, Henter J-I.  Fatal hemolytic anemia and intruterine death caused by anti-M immunization.  Transfusion 2007; 47: 911-917.

There are two papers concerning anti-M in the Japanese population are as follows (the first quoted by Geoff in his book; the second by a group of us in a BSH Guideline).

Yasuda H, Nollet K, Ohto H.  A review of hemolytic disease of the fetus and newborn due to MN incompatibility in Japan.  Vox Sang 2009; 97 (Suppl.1): 125 (Abstract).

Yasuda H, Ohto H, Nollet KE, Kawabata K, Saito S, Yagi Y, Neggishi Y, Ishida A.  Hemolytic disease of the fetus and newborn with late-onset anemia due to anti-M:  a case report and review of the Japanese literature.  Transfusion Medicine Reviews 2014; 28: 1-6.

Klein and Anstee in Mollison's Blood Transfusion in Clinical Medicine 12th edition, do not see anti-M causing HDFN as common enough even to mention it!

This was a bit of a "rush job" in the end, so I hope it is of some use, but, if not, please get back to me.

Thank you shily.

Thanks Dansket - have you stopped laughing at me yet????????????!!!!!!!!!!!!!!!!!!!!!!!!!

Ouch!  I did that once - it hurts.  You have my sympathy.

Yes thanks Donna, and, PLEASE, don't abandon PathLabTalk; your wisdom is required!

Ah, that explains it; I'll tell you why in a minute!

If either anti-D or anti-c is only detected by an enzyme technique, but not by a straightforward IAT (that is, with untreated red cells), then we should not report the quantification results.  The same applies for other specificities, such as anti-K, anti-Jk^a, anti-whatever; if we only detect the antibody using enzyme-treated red cells, we should not report a titre, and yes, you are right, an antibody detected by "enzyme-only" techniques has never been implicated in a clinically significant case of HDFN.

Now then, why did I say "that explains it"?  The answer is that quantification is no longer performed at Tooting, but is performed in Colindale.  The first time a sample comes in during a pregnancy, which contains either an anti-D or an anti-c (or, God forbid, both!), Tooting does the serology, but a sample of the plasma is sent over to Colindale on the same day, and they (usually) perform the quantification on the same day, and enter it into the national computer.  Once this is done, it is almost impossible (not quite, but almost impossible) to take it back off again, and involves paperwork equivalent to an old fashion telephone book for the Quality Department.  After that, however, and as happened in your case, the quantification is not reported (and may not even be performed) unless the antibody has strengthened, and reacts by a "normal" IAT.

All that having been said, it still is wrong that "Enzyme Technique" has been used, rather than "Enzyme IAT" and, although I am no longer Head of the RCI Laboratory at Tooting (having taken over a national position as Reference Service Manager - Training), I am still based at Tooting, and will go to the Laboratory tomorrow and give them a good kicking!!!!!!!!  All aspects of our reports should always be accurate!

Best wishes,

Malcolm

No, between you and me, I think that the reports may have been wrong!

NHSBT RCI Laboratories used to use red cells treated with papain in a direct agglutination method, but then went over to using red cells treated with papain in an IAT, because we found that we got less "rubbish" reactions, and an increase in sensitivity.  However, the option to use either the term "Enzyme IAT" and "Enzyme Technique" remain on the computer.  It is pedantic of me to say that, in reality, an "Enzyme IAT" is an "Enzyme Technique", and so, in reality, the report isn't exactly incorrect, but I know what you mean; it is confusing.  What confuses me more is, if the anti-c was not detected by a straightforward IAT in the first place (i.e. the red cells were not papain-treated), why an anti-c level was reported in the first place; it should not have been.

I hope that assuages any dooubts you may have, but, if not, please feel free to get back to me.

Kindest regards,

Malcolm

Don't fret; I am about the same age as you, and it's been an enjoyable ride so far!!!!!!!!!!!!!!!!!!

No problem Steve.

The policy was changed because so many of our hospitals were using gCAT that, as you say, it was causing cross-matching issues at the hospitals.  According to the BCSH Guidelines, if there are no clinically significant antibodies present, they could cross-match by "immediate spin" technique or by electronic issue.  However, so many hospital Chief Biomedical Scientists were too scared to do this, or let their staff do it, that we found we were having to cross-match loads of units for them (for which we did not have sufficient staff), and so our Testing Department started to M type more units (but, as explained above, not enough)!

Hi Steve,

Thank you for asking me.

What we used to do is to is as follows.  In the case of someone requiring a transfusion, we would test the antibody specificity by gel column agglutination technology (gCAT), and, if there was an anti-M present, we would test the plasma against two examples of M+N- red cells by pre-warmed, warm-washed LISS tube IAT at 37^oC (obviously, these red cells would have to be negative for antigens against which the patient has also made an antibody).  If the anti-M did not react by the tube technique, we would ignore the anti-M, and just give cross-match compatible blood.  From then on, unless there was an increase in the avidity of the anti-M by gCAT, we would not bother to perform the testing by the tube technique.  Despite what you may read from Prof. John Judd, for whom I have the greatest respect I may add, we have never had any problems of "warming away" clinically significant antibodies (unless we were just plain lucky), by dint of the fact that we did not cause a transfusion reaction in two decades!  On the other hand, once the anti-M is detected by the tube IAT, we would respect it from then onwards, and cross-match M Negative blood.

In the case of a pregnancy, we would test the anti-M by gCAT, but would do the LISS tube screen on each occasion (but, we didn't test after 38 weeks of gestation, even if this screen was positive.

Nowadays, we (apparently!) have sufficient M Negative units available that we only perform the screening test on pregnant women (in case the baby is affected), but give M Negative units of blood to all transfusion patients with an anti-M, whether it is clinically significant or not (which, I might add, sometimes leaves us struggling to fill requests for blood that is negative for, say, Fy(a-), Jk(b-), because we have already given out these units as they also happened to be M Negative, even if the patient transfused with these units does not have a clinically significant anti-M).

gCAT can give a sort of false positive with anti-M, making it look like it is reacting at 37^oC, because the reactants are introduced to the reaction chamber at room temperature, and a reaction can take place very quickly between an anti-M and M Positive blood at room temperature, then the cassette is put into a 37^oC incubator, but not long enough for the antibody to elute back off, then the cassettes are centrifuged (bringing the sensitised red cells closer together - thus potentiating agglutination) and the columns containing the AHG are slightly acidic - which an anti-M loves!  It is really my only criticism of the gCAT technique.

Lastly, be aware that it is now known that, within the Japanese population, anti-M of low titre has been known to cause quite severe delayed haemolytic disease of the newborn.  If you have a Japanese population within your area, please be aware of this.

I hope that helps somewhat.  Sorry for droaning on for so long.

With best wishes,

Malcolm

Thank you so much shily, and the same to you and your friends and family.

Thanks for the birthday wishes gagpinks.

I'm no doubt being thick, but is what training and education only for RCI staff?  Could you say a bit more, and then I can answer you more fully.  Sorry to be so stupid!

Thank you very much indeed shily.  That's a lovely way to start the day!

With very best wishes,

Malcolm