Auto antibodies

[Lisa J]

Hi I would be gratefull to hear any feedback on how other labs approach this issue, many thanks for reading!

We recently had a patient with a pan reactive autoantibody that needed 4 units cross matched for routine surgey.

The 3 cell antibody screen and IAT and papain panel cells were all positive (the patient had not been transfused with any blood products since since 2009) and the DAT was positive for IgG and C3d.

We referred the sample to our local reference centre who performed an autoadsorbtion and found no clinically significant alloantibodies and recomended that we provide ABO/D and K compatible units for cross match.

My query is regarding the subsequent tests that need to be performed before the issue of red cells by our laboratory.

We are a small lab and dont come across these patients very often and are wondering how other laboratories deal with these issues as we have a slight difference of opinion!!

As we have no autoantibody depleted serum to work with (as this is at the reference centre) but we do have an aditional EDTA sample on the patient should we select the ABO/D and K compatible units as advised and:

Perform an immediate spin crossmatch and issue the units?

or

Perform a cross match with all 4 units using the recipient serum and also set up an auto and only issue the units if they are equal to or weaker in reaction strenght to the cross match?

I understand the logic for the first one but not for the latter completely........We have been told there are no atypical red cell antibodies in the patients serum so what is the purpose of comparing the auto to the crossmatch reactions? The patient has a pan reactive non clinically significant antibody that is reacting with an antigen expressed on the screening cells/panel cells and donor red cells.....even if the reaction is stronger with the donor cells could this be due to the donor cells expressing more of that antigen than the patient?

Say one of the 4 units crossmatched comes up as a strong positive when compared to the other three units that are equal to the auto reaction...........could that indicate that the patient may have an antibody to a low frequency antigen expressed on the donor cells that is not on the panel/screening cells, or would that be masked by the auto antibody anyway or would it contribute to a stronger reaction? Should that sample then have further antibody investigation work done on it?

Very interested in hearing others opinions

many thanks lisa J (UK)

[PAWHITTECAR]

Lisa does your reference centre provide "compatible" units to your hospital? They could crossmatch with the absorbed plasma. We to are a small facility and we send segments of the "least incompatible" units to the reference lab for crossmatch with the absorbed plasma. We then do IS ans gel crossmatches in-house. The units crossmatched were less reactive than the auto and I received a report from the reference lab indicating that they were compatible with the absorbed plasma. I spoke directly to the physician ordering the transfusion and explaing what was going on so he would not be surprised.

[jayinsat]

In the states we typically do as your reference lab suggested and give phenotypically matched PRBC's. We normally DO NOT send the original sample we discovered the reactions with. I highly suggest you redraw and send new samples so you have something left to use.

We perform our crossmatches on the screened units and label them "Least Incompatible". The physician is required to sign an emergency release form acknowledging that the units are phynotypically matched/least incompatible. We have done this many times without incident.

At one facility I worked, we performed In-Vivo crossmatches. This is where you give a 10cc aliquot of the unit and measure pre/post haptoglobin levels.

[PAWHITTECAR]

Oh James you will give me nightmares talking about in-vivo crossmatches....

[jayinsat]

Oh James you will give me nightmares talking about in-vivo crossmatches....

Tell me about it! I had to splash cold water on my face after typing that.

[Malcolm Needs ☆]

Oh Lisa, Lisa, have you not read the 2012 BCSH Guidelines for pre-transfusion compatibility procedures in blood transfusion laboratories, specifically section 7.13.4?

7.13.4 Where alloantibodies have been excluded and IAT crossmatching using unmodified patient‟s plasma cannot be expected to add value to the compatibility testing process (i.e. it is strongly pan-reactive) it may be omitted. An immediate spin crossmatch using unmodified plasma can be used to exclude ABO incompatibility (Lee et al., 2005).

From this, you can see that an "immediate spin" cross-match is perfectly adequate in this situation, and as safe (in terms of the likelihood of the patient having an antibody directed against a low-incidence antigen, and a unit expressing the antigen in question, as electronic issue - and that is pretty safe)!

That having been said, are you still in the Tooting area, or have you moved to another Centre's area?

The reasons I ask are that 1) we haven't performed an auto-adsorption for as far back as I can remember (because it is so rare for us to be able to get enough patient red cells for us to be able to so do) and 2) we would always recommend that, not only is the blood to be transfused ABO, D and K type similar to the patient (it may, of course be group O, when the patient is group A, or D Negative, when the patient is D Positive, etc), but would also recommend that any transfused blood is negative for the antigens C, c, E or e that the patient happens to lack (e.g. if the patient is R1R1, we would recommend c-, E- blood). The reason for this is that it is well documented that transfusion, in itself, can exacerbate an auto-antibody, thus making the recipient more likely to become transfusion-dependent, and we want to avoid the production of any alloantibodies within the Rh and Kell Blood Group Systems, if we possibly can.

Now then, how is the little one?

:blowkiss::blowkiss:

[Lisa J]

In the words of Homer Simpson Doh!!!!! That teaches me not to read my guidelines thoroughly!!!

Thanks for the answer Malcolm....supplied with great detail as I expected!!

Well the little one is now 8 this year and I have produced another more naughtier version who is now 5!! How time flies I remember seeing your little lad in pics years ago and now he is helping you with presentations...a chip of the old block eh? How time flies!!

I am still at the same place but have moved into the TO post so not based predominatly in BT but its still what floats my boat!!

Would there be any chance I could come and have a look at how you deal with these samples it would be a great chance to pass on the knowldege to our Bt trainees who are terrified when something unusual crosses our paths!

Many thanks again Malcolm this forum is really helpfull:D

Oh Lisa, Lisa, have you not read the 2012 BCSH Guidelines for pre-transfusion compatibility procedures in blood transfusion laboratories, specifically section 7.13.4?

7.13.4 Where alloantibodies have been excluded and IAT crossmatching using unmodified patient‟s plasma cannot be expected to add value to the compatibility testing process (i.e. it is strongly pan-reactive) it may be omitted. An immediate spin crossmatch using unmodified plasma can be used to exclude ABO incompatibility (Lee et al., 2005).

From this, you can see that an "immediate spin" cross-match is perfectly adequate in this situation, and as safe (in terms of the likelihood of the patient having an antibody directed against a low-incidence antigen, and a unit expressing the antigen in question, as electronic issue - and that is pretty safe)!

That having been said, are you still in the Tooting area, or have you moved to another Centre's area?

The reasons I ask are that 1) we haven't performed an auto-adsorption for as far back as I can remember (because it is so rare for us to be able to get enough patient red cells for us to be able to so do) and 2) we would always recommend that, not only is the blood to be transfused ABO, D and K type similar to the patient (it may, of course be group O, when the patient is group A, or D Negative, when the patient is D Positive, etc), but would also recommend that any transfused blood is negative for the antigens C, c, E or e that the patient happens to lack (e.g. if the patient is R1R1, we would recommend c-, E- blood). The reason for this is that it is well documented that transfusion, in itself, can exacerbate an auto-antibody, thus making the recipient more likely to become transfusion-dependent, and we want to avoid the production of any alloantibodies within the Rh and Kell Blood Group Systems, if we possibly can.

Now then, how is the little one?

:blowkiss::blowkiss:

[Malcolm Needs ☆]

Well, first of all, I cannot believe that child one is now eight!

Secondly, heartiest congratulations on child two - if I'm only abouy 5 years too late!!!!!!!!!!!!!!!

Yes, Harry knows far, far more than do I about computers - but, frankly, that doesn't say a lot about Harry (although he is pretty clever - gets that from his Mum).

We would be delighted to show you what we do; just give us a ring and Doris (my deputy, who REALLY runs the Department) will work out a mutually agreeable date. It would be wonderful to see you again.

[Lisa J]

Oh my goodness that sounds truly terrifying!

[Lisa J]

Many thanks for the replies all!

[janet]

THANKS Malcolm!!!!

- you say transfusion can "exacerbate ab auto-antibody" - do you try hard to prevent transfusion in these patients? We have an oncologist who orders to transfuse below 90, she signs a release form but these patients seem to continue to be transfusion dependent for months before Prednisone does anything to stop the antibody production. I have read many articles stating transfusion should be avoided but that does not seem to be her practice!?

- I appreciate the reference to BCSH Guidelines stating the IAT crossmatch can be omitted. Our practice is to send the initial sample to our reference lab 8 hours away for autoabsorbtion and full phyenotype, they often send compatible units based on the negative absorbed plasma workup. Our policy is to do a tube IAT crossmatch with full phenotypically matched units from then on, which are never compatible

How often is a workup done on your auto-antibody patients? Seems silly to repeat every 96 hours when everything reacts and you've given phenotypically matched!?

[Malcolm Needs ☆]

THANKS Malcolm!!!!

- you say transfusion can "exacerbate ab auto-antibody" - do you try hard to prevent transfusion in these patients? We have an oncologist who orders to transfuse below 90, she signs a release form but these patients seem to continue to be transfusion dependent for months before Prednisone does anything to stop the antibody production. I have read many articles stating transfusion should be avoided but that does not seem to be her practice!?

- I appreciate the reference to BCSH Guidelines stating the IAT crossmatch can be omitted. Our practice is to send the initial sample to our reference lab 8 hours away for autoabsorbtion and full phyenotype, they often send compatible units based on the negative absorbed plasma workup. Our policy is to do a tube IAT crossmatch with full phenotypically matched units from then on, which are never compatible

How often is a workup done on your auto-antibody patients? Seems silly to repeat every 96 hours when everything reacts and you've given phenotypically matched!?

Yes janet. Any patient who has already made an auto-antibody should be transfused conservatively. The only time that they should be transfused is if there is no alternative. It has been well-known for many years now that, if a patient has already made an auto-antibody, transfusion tends to make the auto-antibody more "clinically significant". That does not mean, of course, that transfusion should be avoided at all costs - it just means that, if there are alternatives, take them, and see if they work.

That all having been said, it is the decision of the physician looking after the patient whether or not to give the transfusion. Nonetheless, it may be an idea for you to alert your own Pathologist to this situation to see if he or she thinks that a word in your Oncologist's ear might not be appropriate. Remember though, some of the drugs that are used by Oncologists are extremely antagonistic to erythropoiesis, and so there may be a very good reason as to why the transfusions are ordered.

The BCSH Guidelines, although I agree with them entirely, refer only to the practice in the UK and are only guidelines, but they are backed up by very good clinical evidence. We are quite happy that, if we have eliminated all evidence of clinically significant alloantibodies after alloadsorption, then it is as safe as it can be to give blood found to be compatible by the "immediate spin" cross-match. THAT DOES NOT MEAN THAT A CLINICALLY SIGNIFICANT ATYPICAL ALLOANTIBODY MAY NOT BE PRESENT IN THE PATIENT'S PLASMA; there is always the chance, however, remote, that we may have adsorbed out an antibody directed against a high-frequency antigen (such as anti-k, anti-Lan, anti-Vel, etc), but we are not going to detect that by cross-matching using the adsorbed plasma, any more than the hospital can detect it using the "immediate spin" cross-match. This is deemed a "safe" practice, following a thorough risk/benefit analysis. In other words, the risk is so remote as to be discounted.

Our national standard operating procedures also state that we should perform a cross-match using the "raw" plasma, as well as the alloadsorbed plasma. Between you, me and "the gate post", I think this is a total and utter waste of time and reagents, as, the whole point of performing alloadsorption studies is because the "raw" plasma is going to be incompatible with any unit cross-matched against it (unless you cross-match such rare units as Rh null, or Wr(b-) or whatever)! I, personally (and it is only a personal opinion) think that an "immediate spin" cross-match is the only logical thing to do under such circumstances; just to ensure that the units are ABO compatible.

We tend to perform a full work-up after 72 hours, as this is what is "described" by our Guidelines. Actually, what our Guidelines say is that, if the patient has been multiply transfused, and has never made an alloantibody, you can be more liberal than performing the work up after every 72 hours, but they don't say how liberal you can be (for, I suspect, legal reasons), and so people send them in to us for the "72 hour" rule - and we just do them!

I hope that all helps.

Malcolm

:fingerscr:fingerscr:fingerscr:fingerscr:fingerscr