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bowerj1

Give E and c negative units?

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I apologize if this has been discussed previously. I'm sure it has but I had a hard time finding it.

In the situation where you have anti-E (but no other antibodies) in a patient that is c antigen negative, and they want to transfuse...in what situations do you give c negative units? Is the rationale that they were likely exposed to c (I understand this part - because of the antigen frequencies) and so they will likely make it if they are exposed again? Is it simply trying to avoid future anti-c creation? I assume if there is an emergency that you'd have to bypass this step and just give E antigen negative blood? What are your policies/practices regarding this?

 

 

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Not all pts form antibodies each time they're transfused, and not against every antigen to which they are phenotypically negative. Futhermore, you wouldn't even know the pt is c= unless you phenotyped; otherwise, you would have only tested and found the anti-E at the time of workup, and stopped there.

What prevents you from matching units that are phenotypically matched, even just the Rh group? That would require the extra resources and tech power to antigen type units. If they only have the anti-E at the date of product order, I don't see why you'd need to tack on additional testing. My lab tries to avoid extra testing if not needed :D

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8 hours ago, Ward_X said:

Not all pts form antibodies each time they're transfused, and not against every antigen to which they are phenotypically negative. Futhermore, you wouldn't even know the pt is c= unless you phenotyped; otherwise, you would have only tested and found the anti-E at the time of workup, and stopped there.

What prevents you from matching units that are phenotypically matched, even just the Rh group? That would require the extra resources and tech power to antigen type units. If they only have the anti-E at the date of product order, I don't see why you'd need to tack on additional testing. My lab tries to avoid extra testing if not needed :D

What Ward_X writes is absolutely true, but the other thing to remember is that anti-E is one of those specificities (anti-Cw is another) that is often made for no apparent reason (I dislike the term "naturally occurring", because something has stimulated it, but often it is neither transfusion, nor pregnancy), and so the fact that an individual has made such an antibody does not necessarily mean that they are prone to making antibodies as a result of transfusion.

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Except that if you know the patient has been transfused in the past, and now has anti-E, and you also know they are c antigen negative, it would be nice if you could avoid having them produce anti-c.  You already would know that they are a responder, and for future transfusions (for, say, a chemo patient), it would be nice if you did not have to screen units for little c.

(Extended phenotyping of patients to avoid transfusing certain types of blood is indeed done for certain cases, such as Dara or sickle-cell patients.)

Scott

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I agree Scott.  Indeed, we would recommend that, if a female of child-bearing potential has an anti-E, and is also c Negative, she be given c Negative, E Negative blood for transfusion, as anti-c is almost as clinically significant in cases of HDFN as anti-D and anti-K.

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In Applied Blood Group Serology, 4th edition, pg. 332, Issitt refers to a study by Shirley et al. on this very topic.  The study concluded that 5 of 27 patients who had anti-E and only received E- units eventually made anti-c.  They suggested this justified the expense and extra time needed to find units that were negative for both E and c.  Issitt however, uses the findings to argue just the opposite, "Those of us (PDI...referring to himself) who believe the E- c- blood should be provided only after the patient has made both anti-E and anti-c, use the finding that none of the 5 patients in this study who made anti-c suffered a delayed transfusion  reaction, to support their view."  

While the Technical Manual states the "some experts advocate for avoiding the transfusion of c positive blood in this situation" obviously, some experts do not.  In an emergent situation, I don't feel the potential time delay in finding or ordering units that are E- and c- is justified when the patient has not demonstrated they have anti-c.  In a routine situation, we recommend E- units, but quote the Technical Manual regarding this situation and let the customer make the decision.

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I wouldn't dispute the findings of Peter Issitt vis-a-vis transfusion reactions, but I was talking in terms of HDFN, and would still say that an anti-c in pregnancy can be extremely serious.

In terms of an emergency situation, I agree with the Technical Manual.

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3 hours ago, SMILLER said:

Except that if you know the patient has been transfused in the past, and now has anti-E, and you also know they are c antigen negative, it would be nice if you could avoid having them produce anti-c.  You already would know that they are a responder, and for future transfusions (for, say, a chemo patient), it would be nice if you did not have to screen units for little c.

(Extended phenotyping of patients to avoid transfusing certain types of blood is indeed done for certain cases, such as Dara or sickle-cell patients.)

Scott

Scott, you are kind of contradicting your self here.  In one sentence you are advocating avoiding the production of anti-c which can only be accomplished by screening units and transfusing c= units.  Then you say it would be nice if you did not have to screen for units.  I see a conflict here.  Bottom line, it's a gamble.  Either you screen for c= units now to prevent anti-c  or you take the chance they won't make anti-c and if they do you start screening units then.  The latter was always my choice. :coffeecup:

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20 hours ago, John C. Staley said:

Scott, you are kind of contradicting your self here.  In one sentence you are advocating avoiding the production of anti-c which can only be accomplished by screening units and transfusing c= units.  Then you say it would be nice if you did not have to screen for units.  I see a conflict here.  Bottom line, it's a gamble.  Either you screen for c= units now to prevent anti-c  or you take the chance they won't make anti-c and if they do you start screening units then.  The latter was always my choice. :coffeecup:

Just from a man-power standpoint, you don't always have the time to "extra" antigen type. I've seen pts with anti-E that receive products on a weekly basis (that happen to be cancer pts) that have yet to make the anti-c. What about the extended billing for antigen typing? It just seems like a gross assumption to believe a pt with an anti-E acquiring a unit of red blood cells will form an anti-c from it (going back to Malcolm, who initially replied that the anti-E could have been made for reasons other than transfusion). I agree with the serological science of why these are seen together, and why the anti-E can lead to the anti-c, but I have trouble justifying the cost of tech/time, reagents, and billing, to go off a hunch that the anti-c is probable.

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Yes, Ward_X, I can see what you mean.  I also tend forget that the UK has the advantage over the USA in that ALL of our units are typed by the blood services for C, c, E, e and K, in addition to ABO and D, and so we don't have to do that testing at a hospital level.

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On 8/26/2019 at 4:45 PM, bowerj1 said:

In the situation where you have anti-E (but no other antibodies) in a patient that is c antigen negative, and they want to transfuse...in what situations do you give c negative units? Is the rationale that they were likely exposed to c (I understand this part - because of the antigen frequencies) and so they will likely make it if they are exposed again? Is it simply trying to avoid future anti-c creation? I assume if there is an emergency that you'd have to bypass this step and just give E antigen negative blood? What are your policies/practices regarding this?

I was told, by a very senior tech, that this convention began pre-automation when instances where an anti-E was identified but occasionally weakly reacting anti-c was missed. This resulted in a change in hospital policy so when the patient has an anti-E and is c= give E=,C= units.  I then assume this practice spread as techs gained seniority and moved to different hospitals.

The improved reagents, panel cells and especially automated methods over the last few decades, plus increased pressure with time and costs may either make this policy redundant or (remain) implemented based on your patient population and experience.

Thoughts anyone

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5 hours ago, Ensis01 said:

 

I was told, by a very senior tech, that this convention began pre-automation when instances where an anti-E was identified but occasionally weakly reacting anti-c was missed. This resulted in a change in hospital policy so when the patient has an anti-E and is c= give E=,C= units.  I then assume this practice spread as techs gained seniority and moved to different hospitals.

The improved reagents, panel cells and especially automated methods over the last few decades, plus increased pressure with time and costs may either make this policy redundant or (remain) implemented based on your patient population and experience.

Thoughts anyone

That observation makes a lot of sense to me.

Also, I think that the comment noted above by StevenB, regarding the unusually lukewarm AABB position, is telling.  If the AABB is not going to take a hard stance on the issue, then routinely screening for little c in these cases seems to not be indicated under most clinical situations -- and certainly not required by any regulatory standard.

(As for my lab, it wasn't that long ago when we were still screening for e negative units for patients making anti-C!)

Scott

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I think how rural you are also plays into this.  We are the only lab that does antibody IDs in a region of rural Oregon the geographic size of a small Scandinavian country. Our blood supplier is 3.5 hours away over a mountain pass and it snows here. I am not 100% convinced that we should do this but the logic behind our policy to avoid causing production of anti-c is because 5 small hospitals with no ABID capabilities would preserve the ability to select Rh negative blood in an emergency and have very good odds of it being compatible in a patient with a known anti-E, but once they have anti-c that option is gone. We can screen for the c antigen here but if we need to find 6 units our odds get ugly and we would rather get them from the supplier--but they are not exactly across town.

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On 8/27/2019 at 7:17 AM, SMILLER said:

Except that if you know the patient has been transfused in the past, and now has anti-E, and you also know they are c antigen negative, it would be nice if you could avoid having them produce anti-c.  You already would know that they are a responder, and for future transfusions (for, say, a chemo patient), it would be nice if you did not have to screen units for little c.

(Extended phenotyping of patients to avoid transfusing certain types of blood is indeed done for certain cases, such as Dara or sickle-cell patients.)

Scott

We antigen match our sickle cell patients who are on chronic transfusion therapy for the five major Rh antigens, Kell, Fya, and Jkb.  At least that is what we started with; it has grown from there.  One of the issues we see in our area is that most of the units are from white donors.

Most if not all of the new patients are typed and matched for V/VS and Jsa.  These antigens are rare to non-existent in whites, but are found in a sizable percentage of blacks.  So when you target black donors to be able to match the Duffy and Kidd antigens, you may be setting your patients up to make anti-V/VS and or anti-Jsa.

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5 hours ago, Baby Banker said:

We antigen match our sickle cell patients who are on chronic transfusion therapy for the five major Rh antigens, Kell, Fya, and Jkb.  At least that is what we started with; it has grown from there.  One of the issues we see in our area is that most of the units are from white donors.

Most if not all of the new patients are typed and matched for V/VS and Jsa.  These antigens are rare to non-existent in whites, but are found in a sizable percentage of blacks.  So when you target black donors to be able to match the Duffy and Kidd antigens, you may be setting your patients up to make anti-V/VS and or anti-Jsa.

Sorry to interrupt, is anti-V/VS clinical significant? I have not met these kind of antibodies before,( I guess because it is not common or not exist among Chinses people)  just out of curiosity:)

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9 hours ago, Malcolm Needs said:

Anti-V and anti-VS have only ever caused very mild delayed transfusion reactions, and only ever caused a positive DAT, rather than clinically significant HDFN.

But I bet they make the V/VS positive unit crossmatch incompatible so you can't use it, right?  And that from a very limited pool of units.

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9 hours ago, Malcolm Needs said:

Anti-V and anti-VS have only ever caused very mild delayed transfusion reactions, and only ever caused a positive DAT, rather than clinically significant HDFN.

They may indeed "cause very mild delayed transfusion reactions", but to a multi-transfused (Sickle Cell Disease, SCD) patient, with often a multitude of other alloantibodies, what would be a typically mild reaction in a "normal" patient can be serious, even fatal in SCD patients, especially if it induces a hyperhemolysis event. SCD patients understandably have very fragile immune systems. It doesn't take much to upset the apple cart.

36 minutes ago, Mabel Adams said:

But I bet they make the V/VS positive unit crossmatch incompatible so you can't use it, right?  And that from a very limited pool of units.

They sure do, especially since many laboratories routinely use the super-sensitive assays like PEG-IAT or CAT (gel/bead technology) for crossmatches.

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43 minutes ago, exlimey said:

They may indeed "cause very mild delayed transfusion reactions", but to a multi-transfused (Sickle Cell Disease, SCD) patient, with often a multitude of other alloantibodies, what would be a typically mild reaction in a "normal" patient can be serious, even fatal in SCD patients, especially if it induces a hyperhemolysis event. SCD patients understandably have very fragile immune systems. It doesn't take much to upset the apple cart.

They sure do, especially since many laboratories routinely use the super-sensitive assays like PEG-IAT or CAT (gel/bead technology) for crossmatches.

The point is that, if the sickle cell patient has multiple antibodies (particularly if they are in crisis, and need an exchange urgently), it is sometimes necessary for the clinicians to make a decision as to which antibodies are "safest to ignore", if not all antibodies can be covered with antigen negative blood.  In such a situation, the V and VS antigens should be amongst those ignored (at least, according to the reactions recorded in the literature, such as the FactsBook and Daniels).

I am aware of the danger of hyperhaemolysis, being a co-author on a few papers on the subject, but, in the circumstances I describe, where completely compatible cannot be provided, and only "suitable blood" can be provided, it can be a choice between the patient possibly dying due to the lack of a transfusion, or giving blood under cover of high dose IvIgG and a steroid, such as methylprednisolone.  The following paper may also be of interest to you - Win N, Almusawy M, Fitzgerald L, Hannah G, Bullock T.  Prevention of hemolytic transfusion reactions with intravenous immunoglobulin prophylaxis in U- patients with anti-U.  Transfusion, 2019; 59: 1916-1920.  doi: 10.1111/trf.15230.

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So the same logic applies as for E & c--avoid stimulating anti-V/VS during more routine transfusions to save yourself the option to have a compatible crossmatch during a crisis when you may be giving V/VS+ blood to save a life.  If the patient has already made anti-V/VS you can still choose to ignore it and give incompatible units because it is a lesser evil but we would mostly feel better if we could avoid giving crossmatch-incompatible blood because it would be hard in the moment to prove that there wasn't an additional antibody directed against a different low incidence antigen.  That's why we do AHG crossmatches I'd say.  Same argument against it of using a precious resource before the patient has made the antibody.

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Well, yes and no Mabel.  Anti-c and anti-E grouping reagents are very easy to come by (if expensive), whereas reagent quality anti-V and/or anti-VS are both like hen's teeth, and so it would be MUCH more difficult to ensure the units are V- and/or VS-, unless you can check by molecular techniques (Leu245Val).

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16 hours ago, Mabel Adams said:

So the same logic applies as for E & c--avoid stimulating anti-V/VS during more routine transfusions to save yourself the option to have a compatible crossmatch during a crisis when you may be giving V/VS+ blood to save a life.  If the patient has already made anti-V/VS you can still choose to ignore it and give incompatible units because it is a lesser evil but we would mostly feel better if we could avoid giving crossmatch-incompatible blood because it would be hard in the moment to prove that there wasn't an additional antibody directed against a different low incidence antigen.  That's why we do AHG crossmatches I'd say.  Same argument against it of using a precious resource before the patient has made the antibody.

This is a very interesting thread, partly ethics, partly practical use of resources, and a large dose of "what if".  In the legal sense, the concept of "Prior Restraint" comes into play  - doing something to prevent a possible event regardless of probability.

So.....a not-so-unrealistic scenario:

The hospital has a patient with anti-K and is required to screen/type a number of units to fill a transfusion order. During the process some donors/donations are identified as K+. What should the facility do with those, knowing full well that they may stimulate an immune response in recipients ?

And.....discuss.....

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24 minutes ago, exlimey said:

This is a very interesting thread, partly ethics, partly practical use of resources, and a large dose of "what if".  In the legal sense, the concept of "Prior Restraint" comes into play  - doing something to prevent a possible event regardless of probability.

So.....a not-so-unrealistic scenario:

The hospital has a patient with anti-K and is required to screen/type a number of units to fill a transfusion order. During the process some donors/donations are identified as K+. What should the facility do with those, knowing full well that they may stimulate an immune response in recipients ?

And.....discuss.....

This goes back to some comments made earlier in this thread.  It is impractical to screen for all antigens for a particular patient that may induce an antibody response.  However, for a patient that is actively producing (or is known to have produced) an antibody for a particular antigen, transfusing known antigen positive blood would clearly not be indicated if it can be avoided.  

Scott

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19 hours ago, Malcolm Needs said:

The point is that, if the sickle cell patient has multiple antibodies (particularly if they are in crisis, and need an exchange urgently), it is sometimes necessary for the clinicians to make a decision as to which antibodies are "safest to ignore", if not all antibodies can be covered with antigen negative blood.  In such a situation, the V and VS antigens should be amongst those ignored (at least, according to the reactions recorded in the literature, such as the FactsBook and Daniels).

I am aware of the danger of hyperhaemolysis, being a co-author on a few papers on the subject, but, in the circumstances I describe, where completely compatible cannot be provided, and only "suitable blood" can be provided, it can be a choice between the patient possibly dying due to the lack of a transfusion, or giving blood under cover of high dose IvIgG and a steroid, such as methylprednisolone.  The following paper may also be of interest to you - Win N, Almusawy M, Fitzgerald L, Hannah G, Bullock T.  Prevention of hemolytic transfusion reactions with intravenous immunoglobulin prophylaxis in U- patients with anti-U.  Transfusion, 2019; 59: 1916-1920.  doi: 10.1111/trf.15230.

We do our best to avoid them having multiple antibodies by...wait for it...antigen matching.  

I agree with Ex-Limey that our sicklers who are prone to stroke have more than enough going on without having even a mild reaction.  

We have had a few patients with hyperhemolysis and they are the very devil to treat.  The ideal would be to stop transfusions, but that is a very difficult decision to make with these patients.  Also, since we are a pediatric facility, the family may decide to go elsewhere to continue transfusions.

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