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Cold Autoantibodies....please inform!!!


klsmith

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Ok, so I am looking for answers, please inform if you have them! If you suspect that a patient has a cold autoantibody after performing a panel, wouldn't warming it clear it up? even in a gel card? or does that make a difference? And when you perform a DAT, wouldn't it be be positive for C3d? If not, then is a true cold? If you warm everything, and repeat the panel in a gel card, and it does not not clear the reactions, (or only reduces the reactions a little) what does that mean?? It just seems like my blood bank tends to lean a lot twards "cold autoantibodies" when panels and screens are inconclusive, or strongly positive across the board, that and prewarming is just the best answer. Could someone please give some feedback on this? I would like to find out as much information as possible on these cold autoantibodies.

Many Thanks!!

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Ok, so I am looking for answers, please inform if you have them! If you suspect that a patient has a cold autoantibody after performing a panel, wouldn't warming it clear it up? even in a gel card? or does that make a difference? And when you perform a DAT, wouldn't it be be positive for C3d? If not, then is a true cold? If you warm everything, and repeat the panel in a gel card, and it does not not clear the reactions, (or only reduces the reactions a little) what does that mean?? It just seems like my blood bank tends to lean a lot twards "cold autoantibodies" when panels and screens are inconclusive, or strongly positive across the board, that and prewarming is just the best answer. Could someone please give some feedback on this? I would like to find out as much information as possible on these cold autoantibodies.

Many Thanks!!

Hi klsmith,

Some "cold" auto-antibodies have a wide thermal amplitude and simply warming them does not necessarily ablate serological reactions. Indeed, Petz and Garratty maintain that a "cold" auto-antibody does not become clinically significant until it reacts at 30oC, which is well above the ambient temperature of most laboratries.

The problem with performing such tests by column agglutination technology is that the well at the top of the column tends to have its own "microclimate". By that, I mean that it is very difficult to bring the air in the well up to temperature, and so the reactants (the serum/plasma and the red cells) are introduced to each other at a lower temperature than may be thought.

In addition, when the cassette is centrifuged, the temperature drops extremely quickly, and some "cold" antibodies can sensitise red cells in microseconds, and so, again, you tend to get positive reactions.

Turning to the DAT, this may not just be C3d positive, or even C3d positive at all. It could be IgM only, IgM+IgA, extremely rarely IgA only or, on occasions, IgG only (think of the antibody that causes paroxysmal cold haemoglobinuria, which is an IgG anti-P), so the fact that the DAT is negative with anti-C3d does not exclude a "cold" auto-antibody.

Once the presence of a "cold" antibody has been proven BEYOND DOUBT, then I would have no problem using a pre-warming technique, BUT, as this is not a particularly popular technique in the USA (see several other threads), I would also have no problem using either plasma treated with dithiothritol or plasma adsorbed with rabbit erythrocyte stroma (the former denaturing IgM molecules - and most "cold" antibodies are IgM [but not all, see above], and the latter adsorbing anti-I [but, beware, they also adsorb several other specificities).

You say that you want to learn more about this subject. In my opinion, and in the opinion of many others, for a definitive description I would recommend Chapters 3 and 5 of Petz LD, Garratty G. Immune Hemolytic Anemias, 2nd edition 2004, Elsevier Inc. It is also a very readable book as a whole (except, perhaps, for the chapter on drug-induced haemolytic anaemias where, I must confess, I had to "bleep over" some of the names of the drugs - far too complicated for me!!!!!!!!).

Hope that helps a little bit.

Malcolm

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You say that you want to learn more about this subject. In my opinion, and in the opinion of many others, for a definitive description I would recommend Chapters 3 and 5 of Petz LD, Garratty G. Immune Hemolytic Anemias, 2nd edition 2004, Elsevier Inc. It is also a very readable book as a whole (except, perhaps, for the chapter on drug-induced haemolytic anaemias where, I must confess, I had to "bleep over" some of the names of the drugs - far too complicated for me!!!!!!!!).

Hope that helps a little bit.

Malcolm

Malcolm,

I looked for the text you mentioned. It is out of print. Do you have any idea or any way of finding out (you seem to have an extensive network after all) if there is another edition in the works? The brief excerpts I could find looked promising.

Thanks

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Malcolm,

I looked for the text you mentioned. It is out of print. Do you have any idea or any way of finding out (you seem to have an extensive network after all) if there is another edition in the works? The brief excerpts I could find looked promising.

Thanks

I don't know if another is in the pipeline Deny. I'll email George and try to find out, and then get back to you.

I got an out of office returning on 29.10.12.

Edited by Malcolm Needs
Update.
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Do prewarming with caution; you can miss clinically significant antibodies.

The data discussed in Leger R, Garratty G. Weakening or loss of antibody reactivity after prewarm technique. Transfusion. 2003 Nov;43(11):1611-4, and the articles listed below are germane to any policy development for the use of prewarmed testing in the blood bank laboratory.

  • Mallory, D: Controversies in transfusion medicine. Prewarmed tests: pro - why, when, and how - not if. Transfusion 1995 35: 268-270.
  • Judd, WJ: Controversies in transfusion medicine. Prewarmed tests: con. Transfusion 1995 35: 271-275.


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Oh no problem Malcolm. I understand the sieve-like feeling. I am trying to decide how to proceed. The only copies I have been able to find for sale are used and start at $500!! I did find an option to download the book a chapter at a time for about $32 each, but hate to pursue that route if it can be avoided. Thanks for any help.

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So I have another question related to cold antibodies, and this came up at work just in the last two weeks: I found a cold antibody in an oncology patient, that was not picked up in gel, but was discovered upon investigation of incompatible immediate spin crossmatch in tube. I reran the screen in tube, and also did a cold panel, and sure enough, the cold was only reacting at room temp and colder. I got the crossmatch to be compatible, prewarmed, and when I did up the paperwork for the units, I put a recommendation that a blood warmer could be used during infusion, just as a heads-up, if the patient's doctor wanted to do that, and then our supervisor sort of slapped my wrist on that one. I was told to never write notes on the transfusion paperwork, and a blood warmer should only be used if the cold antibody is reacting at 37 degrees.

What do you all think? I don't see the harm in alerting the people performing the infusion, of things that may be helpful to them, and I just figured why take a chance with an oncology patient, regardless of what the antibody is. Basically I think there's a lot worse offenses that can be had in blood bank, and those were minor in comparison to some, but then, too, this supervisor doesn't always like me all the time and I go through periods where it seems like there's fault-finding just for the glory of power and one-up-manship. . . ..

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So I have another question related to cold antibodies, and this came up at work just in the last two weeks: I found a cold antibody in an oncology patient, that was not picked up in gel, but was discovered upon investigation of incompatible immediate spin crossmatch in tube. I reran the screen in tube, and also did a cold panel, and sure enough, the cold was only reacting at room temp and colder. I got the crossmatch to be compatible, prewarmed, and when I did up the paperwork for the units, I put a recommendation that a blood warmer could be used during infusion, just as a heads-up, if the patient's doctor wanted to do that, and then our supervisor sort of slapped my wrist on that one. I was told to never write notes on the transfusion paperwork, and a blood warmer should only be used if the cold antibody is reacting at 37 degrees.

What do you all think? I don't see the harm in alerting the people performing the infusion, of things that may be helpful to them, and I just figured why take a chance with an oncology patient, regardless of what the antibody is. Basically I think there's a lot worse offenses that can be had in blood bank, and those were minor in comparison to some, but then, too, this supervisor doesn't always like me all the time and I go through periods where it seems like there's fault-finding just for the glory of power and one-up-manship. . . ..

I have it in my procedure similar to what you supervisor is saying. We only recommend the blood warmer if the Ab is demonstrating at 37. We require a physician order to use the blood warmer. The order can come from the pathologist if the cold Ab is detected in BB only. The only other time a Blood Warmer is used in our facility is for a Massive Transfusion or in the OR.

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^^Thanks, all! I was just sort of questioning it, and wondering what other places do, because with this particular supervisor where I work, sometimes the line between "is that right" and "is she just picking on me", gets blurred at times. ...

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Recommending a blood warmer when a cold antibody is present seems to make sense. Since the blood bank tech is observing agglutination at roomtemp or warmer (if it is interfering with the gel screen), why wouldn't you want to recommend a blood warmer? Granted, these antibodies are rarely significant, but I'm not aware of any disadvantages to using a blood warmer (that is if used correctly). Again, the operative is "recommend". Requiring a blood warmer would take a Doctor's or pathologist's order.

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Recommending a blood warmer when a cold antibody is present seems to make sense. Since the blood bank tech is observing agglutination at roomtemp or warmer (if it is interfering with the gel screen), why wouldn't you want to recommend a blood warmer? Granted, these antibodies are rarely significant, but I'm not aware of any disadvantages to using a blood warmer (that is if used correctly). Again, the operative is "recommend". Requiring a blood warmer would take a Doctor's or pathologist's order.

My thought exactly-- I figured it certainly would not harm the patient, and was just a heads-up. All I wrote was "may want to consider use of blood warmer during infusion".

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During my training I had to wait for my state license to round on patients with the doctors. I inquired why and was told that I may say something that might influence the doctor’s judgment and medico-legally, with no license, it could cause a law suit. So the sup is following the law and I do not think it is personal in this case. Good luck.

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Ok, a list of 'agree/disagree' items here:

I agree with your supervisor on one plane: Don't write things on documents unless you are instructed to do so. It's very important that things don't 'depend on who is working this shift' ... Blood Banking is a team sport and demands consistency.

I disagree with the 'use a blood warmer only if the cold agglutinin reacts at 37C'. If that's the case, what are you circumventing if the antibody reacts at 37 and you are transfusing at 37? Nothing. The idea of using a blood warmer is to keep the temperature of the transfusion ABOVE reaction temperature. If you have a cold agglutinin with a thermal amplitude above 30C, a blood warmer is not going to change the reactivity and the MD needs to start thinking about reducing the antibody concentration and/or production (pheresis, medication) rather than a risky transfusion ... the patient will destroy the donor RBCs just as quickly as the auto RBCs and may even exacerbate the problem (introducing new antigens, stimulate the immune system).

I agree with your 'caution, best to use a blood warmer': To assure we are all applying the same rules for every patient, I have instructed my staff to issue RBCs with a blood warmer if they see a demonstrable cold agglutinin at the Immediate Spin/Room Temperature phase (we routinely perform this phase with pooled O cells during initial pretransfusion testing to look for 'room temperature/close to infusion temperature' cold agglutinins and rouleux so we have no such surprises later during crossmatching). Is a blood warmer always needed for these cases? Probably not ... but it is the safer side of caution and provides for continuity of a policy. We can do this automatically because it is written into our procedure which is in reality our Medical Director's instructions to us ... yes, she signs all our procedures ... hence, it is a physician's order.

Maybe your supervisor will consider putting such a policy/procedure in place for everyone to follow ... rather than you acting on your own.

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the patient will destroy the donor RBCs just as quickly as the auto RBCs

Possibly quicker.

nOften clinically ineffective, asthe transfused donor cells are rapidly haemolysed by active C3b in the plasma,which binds to virgin CR1 sites on transfused red cells.

nThe autologous cells arerelatively resistant to C3b haemolysis, as all CR1 sites are blocked by C3d/g moities.

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Ok, a list of 'agree/disagree' items here:

I agree with your supervisor on one plane: Don't write things on documents unless you are instructed to do so. It's very important that things don't 'depend on who is working this shift' ... Blood Banking is a team sport and demands consistency.

I disagree with the 'use a blood warmer only if the cold agglutinin reacts at 37C'. If that's the case, what are you circumventing if the antibody reacts at 37 and you are transfusing at 37? Nothing. The idea of using a blood warmer is to keep the temperature of the transfusion ABOVE reaction temperature. If you have a cold agglutinin with a thermal amplitude above 30C, a blood warmer is not going to change the reactivity and the MD needs to start thinking about reducing the antibody concentration and/or production (pheresis, medication) rather than a risky transfusion ... the patient will destroy the donor RBCs just as quickly as the auto RBCs and may even exacerbate the problem (introducing new antigens, stimulate the immune system).

I agree with your 'caution, best to use a blood warmer': To assure we are all applying the same rules for every patient, I have instructed my staff to issue RBCs with a blood warmer if they see a demonstrable cold agglutinin at the Immediate Spin/Room Temperature phase (we routinely perform this phase with pooled O cells during initial pretransfusion testing to look for 'room temperature/close to infusion temperature' cold agglutinins and rouleux so we have no such surprises later during crossmatching). Is a blood warmer always needed for these cases? Probably not ... but it is the safer side of caution and provides for continuity of a policy. We can do this automatically because it is written into our procedure which is in reality our Medical Director's instructions to us ... yes, she signs all our procedures ... hence, it is a physician's order.

Maybe your supervisor will consider putting such a policy/procedure in place for everyone to follow ... rather than you acting on your own.

Thanks, Malcolm and Liz too--that was sort of my rationale, that the antibody was reacting at room temp, the blood will be infused at room temp, and warming it a bit would be an extra caution to avoid having the antibody react, especially where this was a cancer patient; enough problems just having cancer without throwing in antibodies on top of it.

It was actually somewhat of a surprise to me, about not writing things on the transfusion paperwork--we write stuff all the time in the way of our initials, date and time when signing it out, if the patient location changes, we just cross off and initial the change after writing the new location, or if it's a split unit, we'll write "Aliquot A or B"--all stuff that is helpful to the physician and infusionist. I don't think we have a policy about the actual transfusion paperwork and making notations on it, and I'll have to look, but where I work, the rules are sometimes made up as we go along, based on what the day shift techs think. I've made notations here and there on the paperwork in the past and have not gotten any flac until now, so that's why I wondered if it was for real or if I was paranoid.

So yeah, we really need a policy in place, but I'm not going to be the one to suggest it--it's best to stay under the radar at times, depending on the supervisor's mood. . .

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I think JPCroke has some good points. If you make a recommendation on the transfusion slip it now becomes part of the legal medical record. In the unlikely event that there would be a problem with the transfusion (not that I think there would be) and your notation is not in the SOP, the legal profession could have a field day with this.

It is great that you are keeping the patient in mind. As a former supervisor I saw way too many techs just going through the motions and some of them would never even have though of using a blood warmer. And I've also had supervisors that I felt were "picking on me". That's unprofessional behavior but you can't control that!

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