Cold Agglutinin Titer

[demik]

I work in a small hospital and we still do the cold aggl. titer for pneumonia.We used to do a kit test til it was discontinued.For some reason this procedure was deligated to my department (blood bank) and I was wondering if anyone else did this test or perhaps another version of it.If so what kind of controls do you use?

[janet]

Our T.S. does cold agglutinins....not a kit method, our control is a negative only: Saline instead of the patient plasma titrations against the 2% pooled O cells, all incubated at 4C overnight.

[Aileen]

I have 2 different procedures of cold agglutinin in my hands and this confused me which one is correct.... Can someone please share their procedure . Thanks in advance.

[bevdu]

my control is the same as janet. the 8th tube is saline only (no patient plasma).

while we are on the subject, though, how do you do proficiency testing on this

test method?

there is not a CAP survey available for it, is there?

we currently have two techs set up the titer. this is done semi-annually.

i would appreciate any input!!

[L106]

Our Serology Dept. dropped the test several years ago.

[Malcolm Needs ☆]

The titre of a cold auto-antibody, rather like the specificity of a cold auto-antibody, is rarely of any clinical significance whatsoever.

What really is of clinical significance is the thermal amplitude.

If it reacts at 30oC or above, it is almost certainly clinically significant, and then it may be worthwhile doing a titre and, very, very rarely, a specificity (but the specificity only tells you, even in most of these cases, the likely prognosis).

[tbostock]

For the reason that Malcolm states, and that we were doing them only rarely, we dropped the test this year. If a physician insists on one, we collect it and send it out to a reference lab.

[BankerGirl]

my control is the same as janet. the 8th tube is saline only (no patient plasma).

while we are on the subject, though, how do you do proficiency testing on this

test method?

there is not a CAP survey available for it, is there?

we currently have two techs set up the titer. this is done semi-annually.

i would appreciate any input!!

Our serology department does the same thing, however they carry it out to 12 tubes. Our proficiency is the same, as well.

[L106]

I know it's often difficult to figure out what and how to accomplish Proficiency Testing for a particular procedure when no commercial proficiency sample is available, but I don't think that having two different techs doing the test meets the intention of the proficiency testing requirement.

If the two techs perform the test and arrive at the same answer, that means that both techs are following the procedure as it is written. (Actually, this is "competency testing" rather than "proficiency testing".) It does not necessarily mean that the test procedure is testing what it is supposed to test. I think a better way to achieve proficiency testing for these procedures would be to (at least twice a year):

1. Perform the testing by your procedure, then make arrangements with another lab to perform their testing procedure on an aliquot of your sample. If your testing results are the same (or reasonably close), it gives you more assurance that you are detecting/testing for what you think you are testing for. (Does that rambling make sense???) OR:

2. Do like a mini-investigative case study to demonstrate whether your testing results correlate with the patient's clinical findings and perhaps other laboratory results. An example is our Lui Freeze Thaw Elution method: We document the newborn's DAT results, the Lui Eluate results, mother and baby's ABO/Rh results, mother's Antibody Screening results, and serial bilirubin levels done on the infant, and possibly review the baby's chart for evidence of jaundice, etc. All that info together should tell you if the Lui Elution results make valid "sense".

Grant you, neither of these is "ideal" but I think they do a little better job of assuring that you test procedure is testing for the analyte you think you are testing.

[Malcolm Needs ☆]

Our serology department does the same thing, however they carry it out to 12 tubes. Our proficiency is the same, as well.

But why are you doing the titration in the first place?

What does it tel you (or the Clinician)?

:confused::confused:

[BankerGirl]

Malcolm,

This is a very old test for mycoplasma pneumonia. I don't know if it is of much clinical significance, but we still have docs that insist on ordering it. I found the following reference:

"After M. pneumoniae infection, the anti-I levels may increase considerably, and occasionally, enormous increases may occur to titers of >1:30,000. "

Kliegman: Nelson Textbook of Pediatrics, 18th ed.; Chapter 464 - Hemolytic Anemias Resulting from Extracellular Factors >> AUTOIMMUNE HEMOLYTIC ANEMIAS ASSOCIATED WITH “COLD†ANTIBODIES

[Malcolm Needs ☆]

Malcolm,

This is a very old test for mycoplasma pneumonia. I don't know if it is of much clinical significance, but we still have docs that insist on ordering it. I found the following reference:

"After M. pneumoniae infection, the anti-I levels may increase considerably, and occasionally, enormous increases may occur to titers of >1:30,000. "

Kliegman: Nelson Textbook of Pediatrics, 18th ed.; Chapter 464 - Hemolytic Anemias Resulting from Extracellular Factors >> AUTOIMMUNE HEMOLYTIC ANEMIAS ASSOCIATED WITH “COLD†ANTIBODIES

I'm sorry to be a pain and disagree (I really am) but it is only testing a symptom, and is not a diagnostic test. The diagnostic test is the result from Microbiology. I totally agree that Mycoplasma pneumonia can have this effect, but there are also other causes (but I do sympathise if the doctors insist - there is not much you can do, except suggest to them they read Petz and Garratty - and I can just see them doing that!!!!!!!!).

Once again, apologies for being an old grouch!

:o:o:o:o:o

[Clarest]

Hi Malcolm,

 

As you said, if we do the thermal amplitude and it reacts at 30C or above, can we just do a titre at 30C? Our current policy is doing the thermal amplitude first, if it's positive, we do the titre at all temperatures which have positive reactions. For example, if the thermal amplitude test shows positive reactions at  30C, 22C, 15C and 4C,  we have to set up one set of titres for each of the above temperature. Sometimes, our technologist has to set up more than 60 tubes for a cold agglutinin titre. The procedure is tedious and does not make sense at all !!! The hospital I previously worked for has a different cold agglutinin policy which is after the thermal amplitude test, do the titre at the highest temperature which has positive reactions. However, the highest temperature could be 4C, 15C, 22C, 30C, 32C or 37C. Do you have any reference that I can use it to convince our medical director to change our policy? BTW, our medical director is not specialized in transfusion medicine.

On the other hand, in 17th edition of AABB Technical Manual, on page 923 under Method 4-7 Cold Agglutinin Titer Procedure, it says that "Cold-reactive autoantibodies, if present at very high titres, may suggest a pathologic cold agglutinin disease. This may result in overt hemolysis and systemic symptoms and may indicate underlying B-cell hematologic neoplasia". This procedure describes the test done at 4C. I am confused as it seems like 4C titre is very important for clinical purpose, as well.

[Malcolm Needs ☆]

My goodness Clarest, performing titres at each temperature is a complete nightmare, and tells the physician precisely nothing! Most of the time (and time is extremely valuable) must be taken up with your staff writing on the 60 odd tubes, so that they can be safely identified!

I sympathise with you when you say that your medical director is not a specialist in transfusion medicine, but, that notwithstanding, if he/she has taken up the post, then he/she should take the responsibility that comes with the position and ensure that only useful tests are performed, and not overwhelm your staff with this "scatter gun" approach.

I will (grudgingly) agree that a titre at 4oC may serve to show a potentially significant case of CHAD if the titre is extremely high, but, equally, and rarely, a low titre autoantibody at 4oC may also be clinically significant (see, for example, Win N, Needs M, Rahman S, Gold P, Ward S> An unusual case of an acute hemolytic transfusion reaction caused by auto-anti-I. Immunohematology 2011; 27 (3): 101-103), and so I stick to my guns and say that the single most important thing is the thermal range, and that the titre is neither here nor there.

I'm sorry to have to tell you that by far and away the best read for your medical director is the chapter on cold autoantibodies in Petz LD, Garratty G. Immune Hemolytic Anemias. 2nd edition, 2004, Churchill Livingstone. I say I am sorry, because it is quite a read, and from what you say, I am not at all certain that your medical director will so do.

[galvania]

This reminds me of a request I once had to test a patient's Fy phenotype to see if it was possible whether the patient had malaria.......

Surely if you want to know if the patient has m.pneumoniae, you test for m. pneumnoniae........

[Clarest]

The titre of a cold auto-antibody, rather like the specificity of a cold auto-antibody, is rarely of any clinical significance whatsoever.

What really is of clinical significance is the thermal amplitude.

If it reacts at 30oC or above, it is almost certainly clinically significant, and then it may be worthwhile doing a titre and, very, very rarely, a specificity (but the specificity only tells you, even in most of these cases, the likely prognosis).

 

Hi Malcolm,

 

It's me again. When you said "If it reacts at 30oC or above, it is almost certainly clinically significant, and then it may be worthwhile doing a titre", did you mean do a titre at 30C or 4C? Thank you.

[Clarest]

Could anyone please share a good procedure on how to do a thermal amplitude test?