How do you ID cold antibodies (if you do!)?

[Packer Banker]

We currently identify every cold antibody (IH, I, P, etc.) when we have an antibody that reacts at immediate spin. We do a cold mini panel with cord cells, etc. in addition to a full panel when indicated. The major reasons we do this are so we "know what we're pre-warming away" and so we don't miss a Vell. I personally don't see the value in the actual identification of the panagglutinin antibodies.

I would love to present our pathologist with some concrete reasons and facts to support giving up our labor intensive identification procedure. I'm thinking some kind of flow chart that splits the auto control when neg or pos. I understand there are antibodies that could pre-warm away, but I don't think those (like a weak E) would even be picked up when there is a strong cold covering it up. I also realize we do want to ID the P's, M's, etc.

So, what do you do, and why, if you don't mind adding??? Or if you have a good reference source, that would be great too.

Thank you!!

[tbostock]

We don't identify cold agglutinins here since most of them are clinically insignificant. I've never seen the value, if someone can enlighten me on why so much time is spent on identifying these...

We are also not fans of prewarming here; we use it as a very last resort, and are very careful about it.

[David Saikin]

I do the minipanel using screening cells, an auto, A1 &A2 cells if abo compatible, and 2 group O cord cells. I call anti-I, or anti-i or cold auto. I don't get into the Pr's or any other cold specifricities. I look for M depending on my screening cells and cord results. I know I may miss one or two that way, but if they only react in the cold, I'm not missing much.

[Eagle Eye]

we have gel and we don't see as many cold as we used to with tube. Sometime we see cold with gel then we end up doing tube method IS, AHG phase. Do prewarm if OB case, if IgG do titer.

We do not use prewarm unless it is absolutely necessary where patient has auto, multiple antibodies and have cold(anti-M)...we would do prewarm.

[jlemmons]

Does it change the way the patient will be treated if you identify the cold? That is the tact we take and we never bother with the identification. The physician will not do anything different by having this information.

[whbb]

We call all cold reacting antibodies "COLD" because we are not typing the antibody (I,i,H,etc). Also, these types of reactions can be transient. We only worry about these if they react at 37 and/or AHG and we perform a prewarmed antibody screen (AHG) and prewarmed xm (AHG). If they do not react, we call it compatible, and we are done. For extremely strong colds, you may have to use warmed washed cells.

[Malcolm Needs ☆]

Hi Packer Banker,

We never bother to identify the specificity of "cold" antibodies (unless we suspect PCH). All we do is a thermal range (up to 30oC).

This is in line with Petz and Garratty, as far as I am aware.

[ANORRIS]

I agree with whbb

[L106]

I agree with whbb. In my "early" years, if a Cold Auto-Antibody was suspected, we performed a "mini-panel" (similar to what David Sakin described in an earlier post) at room temp, 15 C, and 5 C, etc. Now-a-days we just incubate a 3-Cell Antibody Screen and Auto Control in at 5 C for 15-30 minutes. If results are significantly positive (let's say 3+ to 4+) on all 4 cells we report it as "Cold Auto-Antibody present" (and let it go at that.)

I'm curious.....I haven't seen the "RESt" reagent mentioned in many posts. Are many of you using this reagent? If you aren't using RESt-absorbed plasma and if you are trying to avoid using the Pre-Warmed Technique, are there some other tricks out there that you are using to "work-around" strong Cold Auto-Antibodies that I might not be familiar with?

[Malcolm Needs ☆]

Hi L106,

I must admit, I'm a little curious about the lack of "RESt" being mentioned as well. It is an extremely effective way of getting rid of unwanted, clinically insignificant antibodies...........BUT one of the reasons I didn't mention it was because I was also taking into account that people may not realize that the insert cautions about cross-matching with "RESt" adsorbed plasma (not least because it adsorbs out anti-B - so if, by mistake you grab a unit that is group B for a group O patient - Oh dear!).

That having been said, I also realize that this thread is about antibody identification, rather than cross-matching for a patient with a "cold-reacting" antibody.

Other methods that can be used are auto-adsorption in the cold (4oC), if the patient has not been transfused within the previous 3 months, or alloadsorption at 4oC if they have been transfused, or, as most (but not all, I know {ABO antibodies, anti-P, to mention but two types}) are IgM, treating the plasma with dithiothreitol or ZZAP.

To a certain extent, however, unless you are working in a Reference Laboratory, I can understand the fact that people have been reticent about mentioning such techniques, for the simple reason that, in these days of inspections to be accredited, very few hospital blood banks will see sufficient examples to be competent (or, at least, demonstrably competent) to perform such techniques (or see sufficient cases to justify having such reagents available at all times, when, in most cases, they will time expire before use).

[tbostock]

We stopped using RESt when the cost went up considerably and we realized we were expiring a lot of it. We do a combo of the techniques used above:

Screen at RT and at 4 degrees to confirm cold aggl activity.

Gel sometimes won't show a cold, which is nice, sometimes PEG is helpful.

Cold autoabsorption if the pt has not been transfused in 3 months.

Rule out as much as we can, use prewarmed as a last resort and very carefully.

[Liz]

We stopped using RESt when the cost went up considerably and we realized we were expiring a lot of it. We do a combo of the techniques used above:

Screen at RT and at 4 degrees to confirm cold aggl activity.

Gel sometimes won't show a cold, which is nice, sometimes PEG is helpful.

Cold autoabsorption if the pt has not been transfused in 3 months.

Rule out as much as we can, use prewarmed as a last resort and very carefully.

What brand is your autoabsortion kit?

Thanks

[Malcolm Needs ☆]

Hi Liz,

Obviously, I don't know what tbostock uses, but in the NHSBT (formally the NBS) in England, we papain-treat the patient's own red cells an auto-adsorb at 4oC with these about 4 times. This usually does the trick, as most "cold" auto-antibodies have a specificity of anti-I (with, or without anti-i) or anti-HI.

[Joanne P. Scannell]

I'm reading all this wondering 'why?'. (Again!)

No matter what the antibody specificity is, it is a cold agglutinin and therefore clinically 'insignificant' and you are not going to seek I-neg, Pr-neg, M-neg, Lewis-neg, etc. RBC's. The fact of the matter all this 'clearing' is only to make the BBer feel better, the patient still has this cold agglutinin in his/her system when the seemingly 'compatible' blood is transfused.

So, let's stop fooling ourselves and wasting our time and money.

Reactivity at RT = 'Compatible by Blood Type' and use a blood warmer.

No Reactivity at 37oC = patient has no clinically significant antibodies = no 'AHG' crossmatch is required. You are done!

Yes Reactivity at 37oC = Measures are needed to circumvent the cold agglutinin ONLY to see if there is something clinically significant 'under it'. We have found that prewarming will help us see our way clearly in most (if not close to all) of our cases. (Face it, high titer, broad thermal amplitude, persistent 'cold agglutinins' are not common ... and we are using Anti-IgG now so we don't see these 'colds' as much as we did with Poly AHG.)

YES, I know that 'prewarming' is to be use with caution! Gone are the old days where all we had was albumin (requiring a 37oC spin/reading) and 'Poly AHG' (and it was indeed very POLY in those days!). Contrary to popular belief, 'Prewarm' does not mean 'no enhancement medium' (although sometimes, that's what it takes). So, you CAN prewarm PEG or Gel, therefore you will be 'circumnavigating' without sacrificing sensitivity.

It's very simple really.

[Malcolm Needs ☆]

I agree entirely with you JPCroke.

The only time we will fiddle about is if the "cold" agglutinin has a very wide thermal range and interferes with us excluding clinically significant alloantibodies at 37oC.

Thermal range will be done, if a real case of CHAD is suspected (but not a titre or a specificity) and, if my Consultant suspects mixed warm and cold AIHA (very rare) we will do a bit more work, but otherwise, like you say, why bother.

[David Saikin]

Malcolm - I see many places using REST routinely in the USA (as an inspector/assessor). Personally, I've never had much use for it, but there are folks that love to run it when appropriate.

[Malcolm Needs ☆]

I must admit, I've never been ahuge user of RESt, although I have used it now and again.

Mostly we either try pre-warm, warm-washed IAT, using a monospecific anti-IgG reagent, or DTT treatment of the plasma, or cold auto- or alloadsorption.

If all of these fail, we pray that the patient moves to another part of England!!!!!!!!!!!!!!!!!!!!

[Joanne P. Scannell]

We used to use RESt routinely, but then woke up and realized we really didn't have to. It's expensive and time consuming and doesn't really give you much more information that prewarming would do.

Yep, she's using that word again ... !

[tbostock]

Just to clarify my response above, we only do cold autoabsorptions or prewarmed if it is so strong in gel that we are unable to rule out clinically significant antibodies. We do not identify colds, I agree with JPCroke that it is usually a waste of time and money, and gives the physician no information that will change his/her treatment of the patient. And if they are only reacting at RT or in the cold, they are not significant.

The only cold agglutinin that would warrant use of a blood warmer here would be a clinically significant hemolytic cold agglutinin (these are pretty rare, where you have a positive DAT, low haptoglobin, etc).

[Malcolm Needs ☆]

I (almost) agree wholeheartedly with you Terry, but we did have a case of an auto-anti-I (low titre, moderate, but not high thermal range) that caused an immediate haemolytic transfusion reaction in a small stature child, when the blood was taken straight from the fridge (in an emergency) and transfused. He was then given blood through a blood warmer and sufferred no further reactions.

This was, I fully admit, a very rare case, involving the small stature, the very cold blood and the urgent need for the transfusion, but the very rare does sometimes happen (Murphy's Law).

[tbostock]

That's a scary one Malcolm. We do use blood warmers routinely in the OR and for massively bleeding trauma patients who are receiving cold blood very quickly to prevent hypothermia/coagulopathy.

[Malcolm Needs ☆]

Actually Terri, I think it was more scary for the hospital than for us at the Reference Laboratory, but the difficult thing for us was to show conclusively that there was no underlying alloantibody (as it was such an unusual situation) and, of course, it happened at night, when we had a relatively inexperienced (but very good) Biomedical Scientist on duty.

I was on the telephone to her most of the night, giving her advice, most of which, fortunately for the patient, she completely ignored!

[L106]

Doesn't it drive you nuts when staff calls you at home for consultation/advice, then turns around and doesn't do what you suggested???

[Malcolm Needs ☆]

Oh absolutely L106. That comment was very much tongue in cheek.

Actually, if they don't do what I suggest (at least as a minimum - they can do more on their own initiative), even when I am wrong (and everyone is wrong sometimes) there will be big trouble the next morning!