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Complement activating cold antibody


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For me a somewhat unusual example, I would appreciate your opinions on it.
                  4C           37C           Prewarmed
Screen        H             1+             neg
Ak panel    H             1+             neg
Auto           H            1+              neg
With routine screen on gelcard (anti-IgG) at 37C all cells became 1+, NaCl tube test at 4C gave lysis with all cells, prewarmed on gelcard (anti-IgG) neg on all cells.
                               Room temp         37C
Forward    A           neg    
                  B           4+    
                 Ctr         neg    
Reverse    A1          2+                      neg
                  B           4+                      3+
Extra reaction in reverse grouping in room temperature    
DAT    IgG    1+
          C3d    2+
Sample stored at 4C overnight gave extensive lysis and an unusable sample 


So a cold antibody that activates compliment, our laboratory rarely see lysis like this.
How do you guys routinely investigate this? Do you do anything more? Cold titer? Recommending a blood warmer?
 

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I have an idea of what I think it might be, but I would hesitate to say without a bit more information concerning the condition and underlying pathology of the patient.

How old is the patient?  Have they recently had something like an atypical pneumonia?

I think, without knowing the answer to the above questions, that the specificity of the antibody MAY be between "anti-O" and "anti-Q".

I would suggest performing an indirect DL-test.

I may well be wrong, OF COURSE, but the attached may help.

Paroxysmal Cold Haemoglobinuria (PCH).pptx

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You are like an encyclopedia :)

Should of course have included some information about the patient. 67 year old woman with anemia. Suspected AIHA, but no established diagnosis. The patient has been moved to a larger regional hospital, so it is not certain we will get the final diagnosis.

So "anti-O" and "anti-Q"? I opened my trusty antigen factsbook, but nothing…  :mellow: do you mind telling me more?

We only perform DL-tests at the request of the department/patient responsible doctor, as we do not perform them in house. Did you perform DL-test routinely?

Edited by Walter Isenheim
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I was joking about the specificity being between "anti-O" and "anti-Q", in that anti-P, the specificity almost always involved in a case of PCH is a "cold-reacting" IgG anti-P that "fixes" complement (and P is between "O" and "Q" in the Western alphabet).  A pretty poor attempt at a joke, I fully admit!

While I am not saying definitely that it is a case of PCH, the fact that the patient has a suspected AIHA, that the auto-antibody appears to be "cold-reacting", that it is IgG and that it also involves activated complement, strongly suggests that this may be the line to go down as an investigation.

We didn't perform a DL test routinely by any manner of means (despite being a London based Red Cell Immunohaematology Laboratory).  It was always discussed between our own Consultant (or, at night, weekends or Bank Holidays) by the on-call Consultant, but all of the staff knew how to perform the test, even if they were a lone worker.  We always used to dread being asked to perform such a test as a lone worker, as it took so long to do!

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2 hours ago, Malcolm Needs said:

The Donath-Landsteiner Test for the Donath-Landsteiner antibody (IgG auto-anti-P that binds complement) that causes PCH (see the PowerPoint I attached above).

I hate to admit it but I don't remember ever hearing about that test in my 35* years in Blood Banking!  I guess you are never too old to learn something new, but remembering it is another story.  Thanks Malcolm.

:coffeecup:

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Thanks Walter for sharing such an interesting case. PCH is definitely something I would investigate in this case, although the hemolysis at 4C is rather atypical in a case of a positive LD test. I would also check for drug induced hemolysis ( An eluate would be informative in this case). I couldn't understand why your NaCl tube test at 4C gave lysis as well... (this reminded me of a time when one of my coworkers were getting such weird reactions ....turns out she somehow was using DI water instead of blood bank saline!

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