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Cold Agglutinin Panels


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I have to ask because we are getting pushback from our Pathologist about the clinical relevance of this very outdated test. Does anyone still perform Cold Panels to identify and determine the difference between Anti-H, -IH, -I, or do you just call it a cold antibody, warm the plasma and call it a day? Does anyone know anything about a hemolytic cold antibody? Thanks in advance.

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Having met both Lawrie Petz and George Garratty, co-authors of their seminal work "Immune Hemolytic Anemias" (in this case, the 2nd edition, 2004, Churchill Livingstone), both of whom having signed my copy of their book, and having written a book review of this work for the British Blood Transfusion Society, I am prepared to put my head above the parapet, and dodge the shots!

The first thing I would say is "my own" (as it were), rather than from either of these two world renowned experts; it is this.  Does it matter one iota what is the specificity of the auto-antibody?  The antibody specificity will make no difference WHATSOEVER to the treatment of the patient, but makes even less sense concerning the patient if they actually require a transfusion.  If the antibody specificity turns out to be anti-H, are we going to transfuse Oh units of blood?  Not likely!  If the antibody specificity turns out to be anti-I, are we going to transfused adult i units of blood?  Not a hope!  If the antibody specificity turns out to be anti-HI, are we going to transfuse Oh, adult i blood?  Not in a million years, as nobody has yet been found who has the Oh, adult i phenotype, and so such donors do not exist.  There is a possibility that someone with atypical paroxysmal cold haemoglobinuria MAY require pp blood, but, boy oh boy, such a situation is disappearingly rare!

So, let's turn to the requirement to perform a titration.  Without a doubt, it is true that most individuals with clinically-significant cold auto-immune haemolytic anaemia (CHAD) have a high titre auto-antibody, but the word "most" does not mean "all".  Once again, I apologise for quoting one of my own publications, we published a case (Win N, Needs M, Rahman S, Gold P, Ward S.  An unusual case of an acute haemolytic transfusion reaction caused by auto-anti-I.  Immunohematology 2011; 27 (3): 101-103.) were the titre of the auto-antibody was quite low, but still caused undesirable clinical sequelae.

Let's turn then, to what is actually useful in the diagnosis and monitoring of CHAD, and, according to the two accepted experts on the subject, the ONLY worthwhile test is to see if the auto-antibody is reactive at STRICTLY 37oC (see the chapters on CHAD in the book by Petz and Garratty).  AHGGGGGGGGGG, that should have been STRICTLY 30oC and above!  Apologies to all.

I hope that helps!

Edited by Malcolm Needs
I am an idiot!
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The key question: Is it auto or allo ? This may be difficult to prove if the patient has been transfused.

If it is an autoantibody, I agree with Malcolm's position - who cares?

However, if the autocontrol is nonreactive, you may have to consider other things. Beware anti-Vel and anti-PP1pk (-Tja). These can behave like cold-reactive AUTO antibodies, i.e., demonstrate panagglutination, abolished reactivity by pre-warmed tests, etc.

There is at least one case (published by Jill Storry) of an anti-Vel that was "dismissed" as a cold auto (it was rendered nonreactive by pre-warming). The patient was transfused with random cells and had a fatal hemolytic reaction.

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22 minutes ago, David Saikin said:

when I do a cold workup I try to run 2 cord cells.  I will report:  probable anti-I (if the cords are negative - I know, Pr abs) or cold agglutinin, specificity undetermined

But David, what difference would knowing the specificity make?

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19 hours ago, Malcolm Needs said:

Having met both Lawrie Petz and George Garratty, co-authors of their seminal work "Immune Hemolytic Anemias" (in this case, the 2nd edition, 2004, Churchill Livingstone), both of whom having signed my copy of their book, and having written a book review of this work for the British Blood Transfusion Society, I am prepared to put my head above the parapet, and dodge the shots!

The first thing I would say is "my own" (as it were), rather than from either of these two world renowned experts; it is this.  Does it matter one iota what is the specificity of the auto-antibody?  The antibody specificity will make no difference WHATSOEVER to the treatment of the patient, but makes even less sense concerning the patient if they actually require a transfusion.  If the antibody specificity turns out to be anti-H, are we going to transfuse Oh units of blood?  Not likely!  If the antibody specificity turns out to be anti-I, are we going to transfused adult i units of blood?  Not a hope!  If the antibody specificity turns out to be anti-HI, are we going to transfuse Oh, adult i blood?  Not in a million years, as nobody has yet been found who has the Oh, adult i phenotype, and so such donors do not exist.  There is a possibility that someone with atypical paroxysmal cold haemoglobinuria MAY require pp blood, but, boy oh boy, such a situation is disappearingly rare!

So, let's turn to the requirement to perform a titration.  Without a doubt, it is true that most individuals with clinically-significant cold auto-immune haemolytic anaemia (CHAD) have a high titre auto-antibody, but the word "most" does not mean "all".  Once again, I apologise for quoting one of my own publications, we published a case (Win N, Needs M, Rahman S, Gold P, Ward S.  An unusual case of an acute haemolytic transfusion reaction caused by auto-anti-I.  Immunohematology 2011; 27 (3): 101-103.) were the titre of the auto-antibody was quite low, but still caused undesirable clinical sequelae.

Let's turn then, to what is actually useful in the diagnosis and monitoring of CHAD, and, according to the two accepted experts on the subject, the ONLY worthwhile test is to see if the auto-antibody is reactive at STRICTLY 37oC (see the chapters on CHAD in the book by Petz and Garratty).

I hope that helps!

If you haven't already, you should keep a copy of this response, Malcolm.  I have lost track of how many times this issue has come up here!

Scott

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2 hours ago, exlimey said:

The key question: Is it auto or allo ? This may be difficult to prove if the patient has been transfused.

If it is an autoantibody, I agree with Malcolm's position - who cares?

However, if the autocontrol is nonreactive, you may have to consider other things. Beware anti-Vel and anti-PP1pk (-Tja). These can behave like cold-reactive AUTO antibodies, i.e., demonstrate panagglutination, abolished reactivity by pre-warmed tests, etc.

There is at least one case (published by Jill Storry) of an anti-Vel that was "dismissed" as a cold auto (it was rendered nonreactive by pre-warming). The patient was transfused with random cells and had a fatal hemolytic reaction.

This is very discomforting information.  How would we determine auto from Vel if it is behaving like an auto?

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4 minutes ago, tkakin said:

This is very discomforting information.  How would we determine auto from Vel if it is behaving like an auto?

First step: Is it reacting with autologous cells ? Fairly easy to make that call, IF the patient is untransfused. If the patient is transfused, it gets more difficult, if not impossible.

Any reasonably competent IRL should be able to help. If necessary, they would be able to perform adsorptions and/or test rare cells. They may even be able to isolate autologous cells from a transfused patient.

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I have lived through a hemolytic transfusion reaction due to anti-Vel with no history.  Reactivity was suggestive of a possible cold agglutinin but had a negative autocontrol (warning #1).  Cold screen with pre-warmed testing was performed - both reactive. ReST adsorptions were performed (x2 since 1 pass did not remove reactivity - warning #2).  Unit was issued was a recommendation to use a blood warmer.

Patient received 90cc and alerted nursing staff of distress symptom of "I'm going to die".  Initial post-transfusion sample demonstrated cherry-red plasma (warning #3).  Patient refused any additional transfusions ....

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Hello everyone, I'm new to PLT and it just so happens that I was put in charge of revising our cold panel SOP.  Do you all have any guidelines on the frequency of performing this test?  Currently, we are performing the test anytime the C3 is positive after reflexing from a positive PSDAT.  Many times, we are repeating the cold screen every 3 days.   i revised the SOP so that if the reactions are 3+/4+ there is no need to go further into RT or 4 degrees.  We've been wasting time by incubating 4+ reactions at IS through to RT and 4 deg. That's out of the way, just need to figure out how often to do the Cold screen.  ONce a month? once every 6 months, once a year?

any input would be appreicated. Thanks in advance

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9 hours ago, applejw said:

I have lived through a hemolytic transfusion reaction due to anti-Vel with no history.  Reactivity was suggestive of a possible cold agglutinin but had a negative autocontrol (warning #1).  Cold screen with pre-warmed testing was performed - both reactive. ReST adsorptions were performed (x2 since 1 pass did not remove reactivity - warning #2).  Unit was issued was a recommendation to use a blood warmer.

Patient received 90cc and alerted nursing staff of distress symptom of "I'm going to die".  Initial post-transfusion sample demonstrated cherry-red plasma (warning #3).  Patient refused any additional transfusions ....

After those warnings were all missed, I think I would be inclined to refuse additional transfusions too.  :disbelief::disbelief::disbelief::disbelief::disbelief:.

Having worked in a Reference Laboratory for most of my 43 odd years in transfusion, I am fully aware of the difficulty of identifying some examples of anti-Vel, but really!

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  • 2 weeks later...
On ‎1‎/‎10‎/‎2018 at 4:12 PM, lady_in_a_labcoat75 said:

Hello everyone, I'm new to PLT and it just so happens that I was put in charge of revising our cold panel SOP.  Do you all have any guidelines on the frequency of performing this test?  Currently, we are performing the test anytime the C3 is positive after reflexing from a positive PSDAT.  Many times, we are repeating the cold screen every 3 days.   i revised the SOP so that if the reactions are 3+/4+ there is no need to go further into RT or 4 degrees.  We've been wasting time by incubating 4+ reactions at IS through to RT and 4 deg. That's out of the way, just need to figure out how often to do the Cold screen.  ONce a month? once every 6 months, once a year?

any input would be appreicated. Thanks in advance

Good work on cutting out unneeded RT incubations!  To clarify, are you talking about a cold agglutinin screen when CAD is suspected or a cold antibody screen?  Just wondering since our SOP does not allow cold antibody screens to be performed routinely.  There is reference for a Cold Agg. screen procedure in the Judd's Methods in Immunohematology, 3rd ed.

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