Cold Agglutinin - does specificity matter?

[janet]

We had a patient transferred to us from an outlying facility. Hgb 64, diagnosis query mantle cell lymphoma. We were unable to get a valid blood group due to interferring cold antibodies:

Anti-A 3+

Anti-B neg

Anti-D 3+

Rh Control neg

A Cell 3+, warmed 2+, cells and plasma warmed then tested 2+, washed and prewarmed1+

B Cell 4+

Historical group from 10 years earlier was APos ...... only way we could get a negative reaction with the A cell was to let it settle at 37 and resuspend WITHOUT spinning (is this valid with all the talk of these IgM antibodies not being detected at 37c??)

Futher testing to identify cold antibody (which strangly did not seem to interfere with obtaining CBC results!):

O screening cell: 3+ room temp, 2+ warmed (thinking of HI)

A Cord cell: 4+ room temp, 4+ warmed (less H,i)

O Cord cell: 4+ room temp, 3+ warmed (Hi)

Gel antibody screen had typical 'cold-mixed field' look, prewarm tube IAT was negative.

We transfused 2 group A units and hgb showed no real increase (to 69). They held off further transfusion until hgb was 46 three days later and gave 2 more A units warmed during infusion this time. Hgb rose to 55!? Droped again to 47 and 2 warmed A units given = 57 hgb. Droped again to 47 and A washed cells with warmer given (thinking if complement was a problem washing the cells would deplete the complement in the unit). Hgb up to 57, then few days later back to 47, more washed/warmed A units gave hgb rise to 62....only to drop the next day to 47. Decided washed cells were not the answer and resumed transfusion of A units with warmer, started him on Prednisone and hgb stayed around 75 (anytime Prednisone was weaned the hgb would drop and retics would fall!).

His final diagnosis is high grade B cell lymphoma - Waldenstrom's.

IgA, IgG normal,IgM elevated (3.53 (Normal 0.4 to 2.3)).

Hemociderin was normal.

Haptoglobin less than 0.12 (low)

LDH 1200 (elevated)

Total Bilirubin 41 (sl. elevated)

There did not seem to be intense intravascular clearance (no hemolysis/icteris in sample) but the patients spleen was grossly enlarged and our pathologist thought the red cells were being sequestered here and then removed. Hematologist said the marrow showed erythroid hyperplasia.

The hematologist called me months later stating she had read an article that Waldenstroms can develop anti-I antibodies, she would really like to figure out specificity to learn from this case.

ANY THOUGHTS ..... I feel it's a pan-agglutinin, we did all we could to figure out specificity!

Edited July 8, 2011 by janet

[janet]

Like I didn't write enought already .... a couple other facts forgotten:

DAT postive (C3d only)

Auto control positive I.S. and warmed I.S. but negative at prewarm tube IAT

[Malcolm Needs ☆]

In CHAD, which this patient obviously had, in addition to his primary diagnosis of Waldenstrom's, plasma antibody levels are usually very high because 90% of IgM antibodies are intravascular.

As they are optimally active in the cold, red cell destruction does not usually start until the thermal range has reached 30oC or above, and this does not usually occur until antibody levels are very high.

Transfusion in CHAD is often clinically ineffective, as the transfused donor cells are rapidly sensitised by active C3b in the plasma, which binds to virgin CR1 sites on the transfused cells.

The autologous cells are relatively resistant to C3b "haemolysis", as all CR1 sites are blocked by C3d/g moities.

The transfusion of donor blood causes a significant release of C5b67 complexes, which cause destruction of autologous, as well as transfused blood (reactive haemolysis).

All that having been said, the specificity of the antibody (except in cases of PCH) does not matter one iota. If his antibody had been anti-I, for example, where are you going to get sufficient adult ii units to maintain a decent Hb level? In this case, the antibody looks like a mixture of anti-I and anti-i anyway.

[Malcolm Needs ☆]

Sorry, had to dash out an pick up my wife and son.

...............If the antibody is an auto-anti-H, you will not be able to support the patient with Oh (Bombay) blood (because there isn't enough in the world!!) and if the antibody is anti-HI or anti-Hi, there are no HI- or Hi negative donors in the world - so the specificity is totally irrelevant.

Even in cases of PCH, it is extremely rare that the patient would require pp blood. It usually resolves itself, and you just keep the patient warm until it has.

[ElinF]

I love reading Malcom's answers...

In CHAD, which this patient obviously had, in addition to his primary diagnosis of Waldenstrom's, plasma antibody levels are usually very high because 90% of IgM antibodies are intravascular.

As they are optimally active in the cold, red cell destruction does not usually start until the thermal range has reached 30oC or above, and this does not usually occur until antibody levels are very high.

Transfusion in CHAD is often clinically ineffective, as the transfused donor cells are rapidly sensitised by active C3b in the plasma, which binds to virgin CR1 sites on the transfused cells.

The autologous cells are relatively resistant to C3b "haemolysis", as all CR1 sites are blocked by C3d/g moities.

The transfusion of donor blood causes a significant release of C5b67 complexes, which cause destruction of autologous, as well as transfused blood (reactive haemolysis).

All that having been said, the specificity of the antibody (except in cases of PCH) does not matter one iota. If his antibody had been anti-I, for example, where are you going to get sufficient adult ii units to maintain a decent Hb level? In this case, the antibody looks like a mixture of anti-I and anti-i anyway.

[Liz]

What is the patient's age?

[L106]

I love reading Malcom's answers...

We all do!!!

[AMcCord]

Interesting case! Great information, Malcolm - thanks. (My Thanks button won't work?!?)

[janet]

56 years old

[Rh-fan]

For transfusion the specificity can not help you because there are no compatible donors. I do think that in case of an anti H (IH, iH, anything with a H in it) it is usefull to now so the exclusion of other antibodies is easier (by using group A cells), so you dont have to prewarm or warm wash your test.

I also want ask the other members what they think of prewarming the reverse grouping. I am not such a big fan of it. When you find (extra) reactions in the reverse grouping you can not determine the ABO bloodgroup. The reason for that is that maybe there are weak antibodies anti A or B present that are pointing you to a subgroup of A or B. These weak antibodies will also not be reactive when you prewarm (that are also IgM antibodies), so you are looking for IgM antibodies in a pre-warm technic. I am more in favor of using A/B cells that are lacking the antigen where the antibodies are directed against or removal of these antibodies (REST, P1 antigen, Le antigen)

Please let me know what you think

(maybe a new thread was better but I hope that you forgive this forum-newbe)

[Malcolm Needs ☆]

Plasma/serum that has been adsorbed using RESt must NEVER be used for the reverse group, or for cross-matching. The insert quite clearly states that it will weaken, or remove, anti-B. If the anti-B is weak to begin with, RESt will certainly remove it, and then you would be able to cross-match group B units for a non-group B recipient.

[Rh-fan]

You are correct about the RESt, it has been a long time that I used it, and I was forgotten the removal of anti B, so that is not a good option,

[labgirl153]

Hey Malcolm...what in your opinion is the best source for fresh complement since as you stated in a "rip-roaring" PCH most of the patient's complement has been expended/tied up.

[Malcolm Needs ☆]

Hey Malcolm...what in your opinion is the best source for fresh complement since as you stated in a "rip-roaring" PCH most of the patient's complement has been expended/tied up.

Hi labgirl153,

The best thing you can use is blood from someone who is group AB, D Positive, with no known or detectable atypical antibodies, with the blood taken into a dry tube (clotted), allowed to clot and then for the clot to retract naturally (none of these new fangled tubes that accelerate clot retraction), spin it down, take off the serum, aliquot it into volumes suitable for what you need, and then freeze it down to at least -30oC ASAP, and hey presto, you've got your source of fresh complement!

[labgirl153]

Good one!