Patients with Sickle Cell Disease

[Malcolm Needs ☆]

Dear Malcolm,

I have not ever seen a sickle cell patient with Anti-Fy3 and had it not been for you metioning it here I would not have heard of it either. Upon reviewing the AABB Technical Manuel I see that there indeed is a Fy3 which I initially thought was another name for Fyb. Interestingly, I came to see that the Duffy antigen is also a genetic combatent of malarial infestation, the same as the sickle cell. If the sickle cell patient produces anti-Fy3 and anti Fya would they necessarily antigen type Fyb positive?

No, they would, by definition, be Fy(a-b-), and a true Fy(a-b-) at that.

As you may (or may not) have seen in another of my posts, most of the Black population who have a red cell type of Fy(a-b-) are, in fact, genetically FYB/FYB or FYB/FY, but have a mutation in the GATA-1 gene that prevents the expression of the Fy( antigen on their red cells. In such a case, however, the Duffy antigen is expressed on other tissue (such as the brain, colon, endothelium lung spleen, thyroid, thymus and kidney. Fy(b+) blood that is transfused to these individuals is not, therefore, "seen" as foreign by their immune system.

In the case of true Fy(a-b-) individuals, however, they will be genetically FY/FY, and will express no Duffy antigens on any tissue within their bodies, and will be Fy-3. In such a case, their immune system will recognise Fy(a+b-), Fy(a+b+) and/or Fy(a-b+), all of which are Fy+3, and can, potentially, produce anti-Fya, anti-Fyb and, crucially, anti-Fy3.

:)

[rravkin@aol.com]

Malcolm,

Thank you for this incredible info. So, with respect to your previous post, the sickle patient that developes the anti Fy3 and anti Fya could be either a Fy(a-b-) with the GATA-1 mutation or the true Fy(a-b-); correct? Is there some propencity for these patients to develope anti-Fy3 and anti Fya only, especially if the patient is a true Fy(a-b-), or were you asking about a rare sighting?

Additionally, do you have any thoughts on the understanding that both Sickle disease and the presence of the Fy antigen are both genetically aquired defences against malarial infestation?

Futhermore, I have taken the previous posts and definitely comprehend the fact that there seems to be a likelyhood of these patients to develope the Rh group and Kell antibodies (along with your lecture) and I was considering an evolutionary order of Antigen expression based on this info where the Rh and Kell systems would be older than the other antigen systems. Do you have any thoughts on this idea or am I taking this info way way way toooo faaarrrr!!!

[Malcolm Needs ☆]

Malcolm,

Thank you for this incredible info. So, with respect to your previous post, the sickle patient that developes the anti Fy3 and anti Fya could be either a Fy(a-b-) with the GATA-1 mutation or the true Fy(a-b-); correct? Is there some propencity for these patients to develope anti-Fy3 and anti Fya only, especially if the patient is a true Fy(a-b-), or were you asking about a rare sighting?

Additionally, do you have any thoughts on the understanding that both Sickle disease and the presence of the Fy antigen are both genetically aquired defences against malarial infestation?

Futhermore, I have taken the previous posts and definitely comprehend the fact that there seems to be a likelyhood of these patients to develope the Rh group and Kell antibodies (along with your lecture) and I was considering an evolutionary order of Antigen expression based on this info where the Rh and Kell systems would be older than the other antigen systems. Do you have any thoughts on this idea or am I taking this info way way way toooo faaarrrr!!!

Hmm, perhaps I didn't explain it as well s you thought, so I'll have another go and put it slightly differently.

What I am about to write is slightly simplistic, so for those that want a deeper explanation, skip this post!

The only person who can produce an anti-Fy3 is a person who is genuinely Fy(a-b-). In other words, they have no functional Duffy genes whatsoever. They not only have no Duffy antigens on their red cells, but also have no Duffy antigens on their tissues. If you like, you can regard anti-Fy3 as anti-total-Fy. They do not have to be sickle patients, by the way. It is just that this antibody is seen most commonly in sickle disease (as opposed to sickle trait or individuals with a normal haemoglobin), because they tend to be multi-transfused.

The individual with the GATA-1 mutation is, if you like, a pseudo-Fy(a-b-), in that their red cells group as Fy(a-b-), but their tissues "group" as Fy(a-b+), and Fy+3. Therefore, they will produce neither anti-Fyb, nor anti-Fy3, because they have these antigens on their tissues, even though they are not expressed on their red cells.

Individuals that produce an anti-Fy3 often produce what appears to be an anti-Fya first (which can be quite strong - a lot stonger than the initial anti-Fy3), but eventually this anti-Fya seems to "merge" into a true anti-Fy3, and the anti-Fya can no longer be detected as a separate antibody (similarly, in the Rh Blood Group System, an individual who goes on to produce an anti-HrB will, serological, first produce an anti-Ce, then an anti-hrB, followed by the full blown anti-HrB - it is almost like a continuum, where the antibody that is eventually going to be produced goes through phases during its development, during which it mimics other specificities). It is only a rare sighting in that a) you don't often see anti-Fy3 (it is rare) and you don't often "catch" an anti-Fy3 in its early stages of development, when it is easy to detect the apparent anti-Fya-like antibody. Having said that, we've had another one this week with anti-C+S+Fya+Fy3+Jkb. I've seen enough of these for a while!!!!!!!!! I want to see a nice, easy anti-D!

I think that there is little doubt (in fact, you can regard it as proven) that both HbS and Fy(a-b-) (of both sorts) have been acquired s a genetic defence against certain strains of malaria, but these are by no means perfect. I can well remember being gob-smacked the fist time I saw a patient who was sickle cell trait and had Plasmodium falciparum. I was working alone on-call in the middle of the night and thought that I had completely mucked up the tests. Fortunately, I was able to telephone one of my bosses, who told me that, although it was an unusual finding, it was not an impossible finding!

There is no doubt that the Rh antigens are very old in terms of anthropology. The Great Apes, amongst other primates do express Rh-like antigens on their red cells, and the RHCE gene is undoubtedly older than the RHD gene. I'm not sure how old the KEL gene is in terms of anthroplogy.

Neither, however, is the oldest. Great Apes also express, at the very least, the A antigen (or, at least, something like it) (the A gene being older than the O or B gene), but, apparently, according to Rob Race and Ruth Sanger, untinned Celeocanths express ome kind of ABO antigen! I think, therefore, you may be going a little far, but hey, at least you are thinking, which is great.

Sorry to have gone on so long.

Malcolm

:):)

[L106]

Please don't apologize, Malcolm. I thought your explanations were very clear and helpful. It takes a special talent to be able to "come down to the students' level" when you are teaching (so that you can keep them with you as you advance to higher concepts.) Thanks for sharing your knowledge with all of us.

[Eagle Eye]

I've seen enough of these for a while!!!!!!!!! I want to see a nice, easy anti-D!

If it's simple anti-D, we will not send the specimen to your lab:):).

[Eagle Eye]

we do have several sickle patients(african americans) who has anti-Fya & anti-Fyb....

.I think one more who made anti-Fy3 after making anti-Fya & Anti-Fyb.

[Malcolm Needs ☆]

I've seen enough of these for a while!!!!!!!!! I want to see a nice, easy anti-D!

If it's simple anti-D, we will not send the specimen to your lab:):).

Yes I know, and therein lies the rub.

When I had just left school, and had the great honour of working as a tiny cog in a huge wheel at the Blood Group Reference Laboratory when it was in London (in the 1970's). At this stage Dr. Bertil Cedegren of Sweden was doing a study on Vel in his country, and was ending samples in for confirmation by Carolyn Giles and Joyce Poole.

I was so callow that, at this stage of my life, I honestly thought that anti-Vel was more common than anti-D, because, of course, nobody ever sent in an anti-D for confirmation!!!!!!!!!!

SOme of my colleagues and friends think that I still live in another world, and they are probably quite correct in this!

:D:D:D:D

[RR1]

I've seen enough of these for a while!!!!!!!!! I want to see a nice, easy anti-D!

If it's simple anti-D, we will not send the specimen to your lab:):).

Oh but aakupaku......it's so much more fun having to deal with patients with weird and wonderful antibodies. At my previous hospital we had quite a few with anti-U, anti-Jsb etc... and about half the total number of patients in the UK with post-transfusion hyper-haemolysis on top of this (though I may be wrong about this- I think there were approx 4). Life was never dull.

[Malcolm Needs ☆]

Oh but aakupaku......it's so much more fun having to deal with patients with weird and wonderful antibodies. At my previous hospital we had quite a few with anti-U, anti-Jsb etc... and about half the total number of patients in the UK with post-transfusion hyper-haemolysis on top of this (though I may be wrong about this- I think there were approx 4). Life was never dull.

Don't forget your patient with anti-HrB who kept us all amused for a while!

:eek::eek:

[rravkin@aol.com]

Disparaging comments removed by site admin.

Please refrain from making such comments.

[Malcolm Needs ☆]

Disparaging comments removed by site admin.

Please refrain from making such comments.

I'm sorry, but I think this post is grossly unfair and unnecessarily rude and personal.

If you go to L106's page, you will see that you are able to access all the posts written by her, and you will see that the vast majority are well-written and very informative, and I, for one, have learned a great deal from what she has submitted.

:angered::shakefist:shakefist:slap:

[heathervaught]

I sincerely hope that such rude and unprofessional posts are not tolerated by this site's administrator and that rravkin's comment will be removed right away. This forum should be used to exchange ideas and provide advice in a professional manner.

Edited March 8, 2010 by heathervaught
Thank you Cliff!

[Cliff]

The disparaging comments have been removed, let's move forward now please.

[rravkin@aol.com]

Cliff,

Thank you for your intervention. I have joined this sight for the same reason that everyone has; an interest in Blood Bank. I frankly felt that some of the commentary made by some of the other posters were very condensending and inappropriate given the fact that this is an international sight visited by individuals with varying background. I certainly have a grat interest in what is dicussed here and would like to proceed without petty condensation and insult. The main proprietors were Malcolm and L106. I think that they should maybe have a sight of thier own if they find it necessary to conduct themselves in this manner.

Now I am ready to proceed.

Thank you.

[Brenda K Hutson]

You theorise upon an interesting concept here. Indeed, of course, steric hinderence is already known about with the ABO group hindering the antigen/antibody reaction between anti-H and H, and the Kell glycoprotein hindering the reaction between anti-Kx and Kx, so, in theory at least, this could happen with the distortion of the sickle cell. However, I think that the distortion is at a gross level, rather than at a microscopic level, and so the antigens, so long as they are evenly spread around the cell surface, and they are numerically high, should still be "available" - but I don't know that for sure.

Yes, there are plenty of cases of sickle cell patients making antibody specificities without first making Rh or K antibodies (I think I mentioned one in a post the other day who had made anti-S+Fya+Fy3+Jka, which kept me up most of the night!).

By the way, have you noticed how many sicklers who go on to make anti-Fy3 seem to produce an anti-Fya (or apparent anti-Fya) first, if you "catch them early enough"?

:confused::confused:

Just caught the last part of this regarding the Fya first. Yes, in fact, I was going to say something about this before but decided not to. That is that when I was working with a lot of sickle cell patients, most of whom are Fy(a-b-), if we were at the point of having to give the patient phenotypically matched because they had made 1 or more antibodies, we did not initially give them Fy(a-b -); we just gave them Fya-. And you are correct, they did not make anti-Fyb.

Second, with regard to your comment about a number of patients who made antibodies other than Rh and/or K first; can I assume then that you are referring to patients who were not receiving the standard of practice Rh, K system compatible RBCs? But I'm sure that if I had access to all of those records again, I would probably be able to come up some also; it is just that it was very rare to get a transfused sickle cell patient who had not been given Rh and K system compatible RBCs. So, a statistical analysis would be difficult.

Thanks,

Brenda

[Brenda K Hutson]

Don't forget your patient with anti-HrB who kept us all amused for a while!

:eek::eek:

I remember 1 SS patient we had when I was a Red Cross supervisor. She had made every antibody possible (including hrb). The only blood that was compatible for her was in Africa (and you have to wait a week to even get that; and then, will it be HIV Neg)? She was admitted to her hospital (for the last time) with a hemoglobin of about 2.6! I called the National Red Cross Reference Lab to discuss our options. In the end, she was sent to hospice. Sad....

Brenda Hutson

[Malcolm Needs ☆]

Cliff,

Thank you for your intervention. I have joined this sight for the same reason that everyone has; an interest in Blood Bank. I frankly felt that some of the commentary made by some of the other posters were very condensending and inappropriate given the fact that this is an international sight visited by individuals with varying background. I certainly have a grat interest in what is dicussed here and would like to proceed without petty condensation and insult. The main proprietors were Malcolm and L106. I think that they should maybe have a sight of thier own if they find it necessary to conduct themselves in this manner.

Now I am ready to proceed.

Thank you.

I didn't think I was being condesending or insulting, but if I was I apologise.

Please, if I my posts ever appear to other members like that, please let me know.

:eek::eek:

[Cliff]

I thank you all for trying to resolve these disagreements politely, and expect that the level of professionalism will continue.

I recommend that since all parties concerned have had their say, that we drop that part of the conversation.

If you have additional concerns, please send me a private message.

[Malcolm Needs ☆]

I agree (although, as I say, if I do come across as patronising and condesending, I apologise and would like members to send me private messages to tell me when I have come across like that - and tell me to get off my high horse)!

:redface::redface:

[rravkin@aol.com]

Dear Cliff, Malcolm, and L106,

Let me briefly state that I find the statement and quotationed comment of L106 post dated 3/6/10 01:02PM of this stream, "It takes a special talent to be able to "come down to the student's level," highly objectionable. This overall post offers absolutely nothing by way of information or thought to the initial thread of this stream. I find this statement to be grossly condescending, insulting, and personally offensive given the fact that it refers to a post offered by Malcolm where he was explaining again a previous post that I did not understand. Look at this post and read it! What else could this post achieve but to condensed and insult. Therefore I strenuously request that it be removed on the grounds of its objectionable content. It invokes the idea that if you do not understand a given post then you have some lesser level of capability to understand and it is very subjectively supported with the statement "Please don't apologize, Malcolm. I thought your explanations were very clear." So L106 thinks that because he or she comprehends a posted message that anyone else who does not is of some lesser comprehending level. This is an insult to everyone who has ever not understood an initial post and has claimed so and requested an explanation. And Malcolm, it was only a request, not a demand; and you and I and everyone here is under know obligation to converse, explain or otherwise. <comments removed by site admin>

You need to remove this post immediately! <site admin disagrees>

And Malcolm, I accept your apology but you need to reconsider your words sometime because in this case it was the seed that provoked the post by L106. I am very surprised that you as an instructor and lecturer are not as up in arms over this post as well because every time a student of yours or participant needed further explanation they were of some lesser level of ability in comprehending according to the very subjective L106.

And I am surprised that there are other posters on this site that are not as up in arms over this very subjective and condescending post as well because according to L106 if anyone of us does not understand a given post then we are all of some lesser standard of intellect according to the subject standard of L106.

I repeat, Cliff, you need to remove the post given by L106 3/6/10 01:02PM. <I also repeat, I disagree - site admin>

[RR1]

I think there has been a complete misunderstanding in what L106 said, she was merely thanking Malcolm (as I had) for a very clear explanation being given. Many of us on this site are also lab managers -with many years experience, but we are not adverse to being taught something new or even given a clearer explanation of things we may have already known.

This site is purely about learning and communicating this to others regardless of how experienced we consider ourselves to be. This requires a far humbler approach, and that is the impression I got from those comments.

[rravkin@aol.com]

RR1,

Thank you for your insight. But let me ask you, if you are not adverse to being taught something new then aren't you a student? In fact we all are. So according to L106 an instructor has to "come down to the student level" so that we become learned. I honestly feel that there is a distinct and subjective level of condensation in that post and I find it insulting and offensive. I agree with everything you say except I really don't see humility in these words.

[Cliff]

Well, I find this most unfortunate, but this thread is now closed.

I have reviewed all of the posts and do not think there was any intentional ill will on any participants part.

Some of the people who responded are amazing serologists, and fabulous teachers - I am grateful they are active participant on this site.

I understand that some people feel that I must remove posts, but I disagree. The posts will remain as they are.

Please refrain from starting new posts to accuse others of wrongdoing, or otherwise make disparaging comments - this will not be tolerated.