Warm Autoantibodies

[cassiepenn]

We recently have a patient that we frequently transfuse that has developed anti-C and anti-JKa, this last time we sent her blood into ARC to work up and they say she has a warm autoantibody. We use gel technology 4 out of 5 units were incompatible. They did the crossmatch on three of the units with tube method and liss and got compatible. How is this possible and is this acceptable. I am tring to figure out a safe way to transfuse her. We have not had any one with an warm autoantibody so we are usure on our next move.

[Yanxia]

I think the gel technology is more sensitive , it is safer than the tube and liss method.

[AMcCord]

Remember that the gel method will really ramp up reactions of warm autos, just as PeG and solid phase will. You can see warm autos with gel that you wouldn't have even detected if your standard method was tube/LISS. (Same holds true if you use PeG, instead of gel.) If you used standard tube/LISS you would have transfused antigen negative units that crossmatched with LISS, probably with no greater risk to the patient. All transfusions to patients with warm autos are a risk and should be avoided whenever possible. Crossmatching antigen neg units with Peg or Gel or solid phase instead of LISS and calling them compatible doesn't necessarily make transfusion any safer with the warm auto. Sometimes sensitivity can get in the way of specificity. When working with warm autos it is sometime helpful to take a step back to LISS to crossmatch antigen negative units, thus avoiding the warm auto, to see if there are any other dangers present (alloantibodies that have gone undetected because they were hiding behind the warm auto). Your reference lab is not following an unusual process.

[Mary**]

:handshakeI agree. We do the same as you do. LISS/AHG was recommended by our reference lab for warm autos. Using Liss/AHG before we had gel seemed safe to us then!

[tbostock]

As per the Technical Manual "patients with warm autoantibodies have a higher rate of alloimmunization (12-40%)". And "in patients with active hemolysis, transfusion may increase hemolysis...". I always try to talk physicians out of transfusing these patients, and I hardly ever win the argument. So we get them to sign a scary statement about higher than normal risk. Sometimes that gets them to change their mind, usually not.

So, yes, you will get better results with LISS, but since it is less sensitive, you may miss an allo.

[adiescast]

The theory with a warm auto is that you can transfuse (antigen negative if the patient has underlying alloantibodies) with relative safety because the antibody tends to destroy transfused cells at about the same rate that it destroys the patient's own cells. Most of the time this seems to be true. The patients tolerate the transfusion pretty well.

We had a very scary one last year with a sickle cell patient. The patient had multiple known antibodies and came in with a new warm autoantibody. We transfused antigen negative blood and the patient went into fulminant hemolysis. We redid all of our work, certain that we must have missed another alloantibody, and found nothing extra. We sent it off to a reference lab and they found nothing else. The warm autoantibody appears to be the culprit in this case. It was nearly fatal. The patient got down to a 1.5 hemoglobin before he stabilized. Several months later, he came back for more transfusions, and the warm autoantibody was gone. Transfusions have been normal ever since.

[tbostock]

Yes, "hyperhemolytic syndrome" in the sickle cell patient. I saw it once many years ago; very frightening and you go crazy trying to find what you may have missed. Our patient did succumb to it, but she was very sick prior to the episode.

[AMcCord]

We've transfused 2 scary ones, hemolyzing their cells and the transfused cells faster than you could say Warm Autoimmune Hemolytic Anemia. Neither had alloantibodies that we or the reference lab could find. Neither had any underlying medical problems that could explain what was happening other than their immune systems just felt like going crazy. Both were worked up extensively for infection, malignancy, etc. Neither were on any medication. No treatment worked. They just stopped hemolyzing as suddenly as they started and both survived, but barely.

We transfused another one with 3 alloantibodies identified before the auto problem started. The first time we saw her, the auto was fairly weak, so we and the reference lab got a full phenotype on her (and we agreed, too!) and found no additional antibodies and managed to get a clean crossmatch with LISS. The next time we saw her, her auto was 4+++++++. Sent that one straight out to reference, who tried 3 absorptions for the book and 2 more for fun and her antibody screen was still all reactive 4++++++++. We gave her phenotypically similar red cells. 3rd time we saw her, same story. 4th time, reference lab begged us to persuade her to move out of state - we assured them that we had already tried that to no avail. Anyway, we transfused her 4 times uneventfully over about 3 months. Saw her 6 months later and her DAT was only weakly positive and haven't seen her since. Go figure!

There have been many more who have received multiple transfusions here with no apparent reactions. Problem is, there is no good way to tell which one will hemolyze and which one won't. Thankfully, most will do OK. It's always nice when these patients are referred for a consult with the hematologist or an oncologist. Those folks generally do a good job of discouraging transfusion.

cassiepenn, the medical director of your blood center (or ARC reference lab - if they are not the same) could be helpful to you. They will talk to your medical director or to the patient's physician about your patient's case and offer some good advice.

[Malcolm Needs ☆]

I think the gel technology is more sensitive , it is safer than the tube and liss method.

I'm sorry shily, but to say that gel technology is safer than the LISS tube IAT is totally untrue.

AMcCord is absolutely correct in saying that it may be more sensitive, but you lose specificity.

If the LISS tube IAT is so dangerous, do you think that it would be the first line of attack at the International Blood Group Reference Laboratory and would have been used by such luminaries as Dr. Carolyn Giles, Dr. Elizabeth (Jan) Ikin, Dr. Kenneth Goldsmith, Dr. Robert Race, Dr. Ruth Sanger, Dr. Arthur Mourant, to name but a few, and do you think it would still be used by people such as Joyce Poole?

:mad::mad::mad:

[Malcolm Needs ☆]

Yes, "hyperhemolytic syndrome" in the sickle cell patient. I saw it once many years ago; very frightening and you go crazy trying to find what you may have missed. Our patient did succumb to it, but she was very sick prior to the episode.

Yes, it is extremely scary!

We usually recommend not transfusing if at all possible, but if it is deemed necessary, using IVIG and methylprenisolone cover. This seems to help.

[cassiepenn]

Thanks everyone for the ideas and thoughts. ARC was able to id anti-e unable to say for sure if allo or auto. They are pretty sure it is auto because every crossmatch is incompatible. They sent us units that are negative for anti-C, anti-e, anti-JKa. Our pathologist talked the oncologist out of the transfusion for know. They are going to recheck hgb on monday. One question I do have is if it is a auto antibody then why did we have one unit that was compatible with gel. She did recieve this unit last sat 7/4/09. She did not have any problems.

Thanks

Cassie

[Stoogiesfreak]

Malcolm, I totally agree with you about Gel and Warm Auto's. In fact we gave up Gel totally in our BB due to many false positive reactions and two cases of antibodies not detect by Gel that the Capture system was able to detect. We do our crossmatching for patient's with Warm Auto with LISS/AHG and have had no issues. As a side note I think the Warm Auto is probably the "scariest" antibody to work with. As far as Gel goes I have sent many a workup to our ARC Reference Lab only to find out that there was nothing present in the serum. Bye, bye Gel! John

[Malcolm Needs ☆]

Ah, don't get me wrong John. I actually like the gel technique, and we use it as a first line of attack for most of our samples.

It's only when we are dealing with auto-immune samples (about 5 a day) that we use the LISS tube technique.

We're performing something like 50 to 60 antibody panels a day, and it is much quicker to perform these in gel, but there is quite definitely a place for the LISS tube technique.

[Stoogiesfreak]

Hi Malcolm,

Your volume surpasses ours by a mile! I can see where Gel would be beneficial to you. Since you obviously have more experience with Gel why did we run into so many positive reactions in Gel and nothing could be found in a panel by our lab or by our local ARC reference lab? We ended up going with Immucor and the Capture methodology and have not had the problem since. Would appreciate your thoughts. We also in our comparison studies fould two samples with antibodies that Gel did not pick up, but the Capture did??

Thanks,

John

[Malcolm Needs ☆]

Thanks everyone for the ideas and thoughts. ARC was able to id anti-e unable to say for sure if allo or auto. They are pretty sure it is auto because every crossmatch is incompatible. They sent us units that are negative for anti-C, anti-e, anti-JKa. Our pathologist talked the oncologist out of the transfusion for know. They are going to recheck hgb on monday. One question I do have is if it is a auto antibody then why did we have one unit that was compatible with gel. She did recieve this unit last sat 7/4/09. She did not have any problems.

Thanks

Cassie

Hi Cassie,

If it were an auto-anti-e, there is a fairly good chance that it would actually be an auto-anti-e-like mimicking antibody. In this case, there would also be a very good chance that this "anti-e" could be adsorbed to extinction by R2R2 red cells.

If it were a genuine allo-anti-e, this would not happen.

With reference to the compatible donor, of interest would be the ethnic origin of the patient in this case, but also of the donor. There is always the chance that the donor had a variant of the Rhe antigen; more so if he or she were of Black ethnic origin.

:confused::confused:.

[Malcolm Needs ☆]

Hi Malcolm,

Your volume surpasses ours by a mile! I can see where Gel would be beneficial to you. Since you obviously have more experience with Gel why did we run into so many positive reactions in Gel and nothing could be found in a panel by our lab or by our local ARC reference lab? We ended up going with Immucor and the Capture methodology and have not had the problem since. Would appreciate your thoughts. We also in our comparison studies fould two samples with antibodies that Gel did not pick up, but the Capture did??

Thanks,

John

Hi John,

Don't forget that I am the manager of a Red Cell Reference Laboratory that covers about 50 hospitals, including at least three large London Teaching Hospitals. This explains the high numbers of panels we perform. This number includes are "number one" panel (as it were), and then panels that are almost all R1R1 and panels that are almost all R2R2, so this boosts our numbers quite a bit. We don't actually have 50 to 60 referred samples a day (thank goodness!).

The answer to your question really depends upon what techniques your local ARC use themselves. As you may have seen in other threads, the gel technique is very sensitive, but is not necessarily as specific as some other techniques. Last night, for example, I dealt with a sample that had a pan-reactive auto-antibody in it reacting by gel enzyme technique (5+). By gel IAT, there was quite clearly an auto-anti-C present (or possibly an auto-anti-Ce, but, hey, who cares at 2 o'clock in the morning, when the exact specificity makes no difference to the treatment of the patient?) and a few scruffy 1+ reactions with some of the other cells in the panel.

By pre-warm, warm-washed LISS tube IAT, using a monospecific anti-IgG reagent, however, there was no evidence of any reactions whatsoever (and yes, I did do all the necessary controls using a weak anti-K, anti-Fya and anti-c for comparison, and adding IgG-coated red cells to the negative tubes, to all those who disparage this technique), so if your ARC does something similar, this could explain the situation.

As to antibodies you are picking up by one technique, but not another, as I have said in other posts, this is of no surprise at all, as these antibodies are derived from humans of course (as opposed to grouping reagents that are usually monoclonal nowadays) and the variable regions of these antibodies will react in different ways in different techniques (slight changes in amino acid residues in the variable region, and the constant regions come to that could explain these variations in reactivity, as does the subclass of IgG being detected by the reagent AHG). Not all antibodies will react by all techniques.

We detected an anti-S by LISS tube IAT a few years ago when I was working in a hospital Blood Bank that was sent around to quite a few different hospitals and the Reference Laboratory where I now work, and this anti-S was only ever picked up by tube technique.

I tend not to worry about antibodies that react only by gel IAt or by solid phase IAT, simply because these techniques are very, very sensitive, and the reactions in gel or solid phase are usually very, very weak (although, conversely, I would recommend antigen negative blood for the patient). On the other hand, I do worry about tube only antibodies, unless they too are very weak.

I hope that these vague ramblings answer some of your questions, but if not, get back to me and I'll give it another go!

:)

[Stoogiesfreak]

Thanks Malcolm. I think you just gave me what the answer I had overlooked! Our reference lab is using LISS/IgG and/or PEGG/IgG tube methodology. That would explain the difference. Anway, we did change from Gel to Capture and it is working nicely for us. We do have a faily large population of Sickle Cell patients and the antibody screens and ID's have been reliable by this method. We only have one patient that is a real "problem child" and she has a Warm, Kell, Fya and U. Also, I am trying Immucors W.A.R.M raagent working with Warn Auto's and so far it has been helpful. You just never know what might be lurking underneath that Warm Auto! Thanks for your information, you certainly answered my question and I look forward to more of your knowledge sharing. I am new to this site, but already have learned things and that is good!

Thanks again,

John

[Malcolm Needs ☆]

Thanks John.

Yes, It's a great site. I, too, am learning things almost daily from it.

[Brenda K Hutson]

Yes, while most warm autoantibodies are not hemolytic, some certainly are. There is also something called hyperhemolysis, where a patient actually hemolyzes the blood and ends up with a lower Hgb than they started with. "Been there seen that" in Sickle Cell Patients (I was a Reference Lab Supervisor in an area with a large population of Sickle Cell patients; they can be very difficult patients from an antibody perspective).

Had another situation of a patient with a Warm Auto-e; not uncommon. This guy was hemolyzing big time, so we were giving him R2R2 blood. However, he continued to hemolyze. When he was down to about a 4 Hgb, I called Dr. Garratty. He explained that in patients who have hemolytic Warm Autoantibodies, it is actually better to give steroids than to continue to transfuse. Continuing to transfuse actually stimulates the immune system and makes it worse. Also, though the Auto Antibody had an Anti-e specificity, there can also be a non-specific element to it that you may not pick up serologically (so the R2R2 was not protection enough). Good outcome; once we stopped transfusing him, he got better!

Brenda Hutson, CLS(ASCP)SBB

[Stoogiesfreak]

Brenda,

Thank you for the added information. We recently ran into a similar situation with hyperhemolysis. The patient started with a 5.4 Hgb and ended up with a Hgb in the 4.5 area after two units. This continues to make me think that a Warm Auto is one of the most dangerous of the antibodies! Again, thanks for the added information. Our patient also had a Warn Auto-e which is not that uncommon when working with auto antibodies. They are great copy cats when they want to be.

John

[Malcolm Needs ☆]

Brenda,

Thank you for the added information. We recently ran into a similar situation with hyperhemolysis. The patient started with a 5.4 Hgb and ended up with a Hgb in the 4.5 area after two units. This continues to make me think that a Warm Auto is one of the most dangerous of the antibodies! Again, thanks for the added information. Our patient also had a Warn Auto-e which is not that uncommon when working with auto antibodies. They are great copy cats when they want to be.

John

What you say is true about warm autos being potentially dangerous, but hyperhaemolysis is more so.

Hyperhaemolysis can strike whether or not there is a warm auto present and whether or not there is an alloantibody present.

It is best to avoid transfusion at all if there is a history of, or worse, an on-going episode of hyperhaemolysis, as it is very often fatal. If transfusion is essential to preserve life, try high-dose IVIG and methylprednisolone.

Edited July 17, 2009 by Malcolm Needs
Spelling okay this time, but the grammer was awful!

[Stoogiesfreak]

Thank you Malcolm. Once again I learned something! I was not aware that hyperhemolysis could take place without a Warm Auto being present. Thanks for this valuable piece of information.

John