Hello

All labs incubate Cold Agglutinin titres at 37C, but there appears to be less of a consensus when it comes to 30C , 22C or even 4C .

What phases should a transfusion service perform to assist clinicians and to be in line with current standards, best practice?

Thanks

Richard

Well, if you follow Petz and Garratty, the "bible" of auto-immune haemolytic anaemias, first of all performing a titre is a total waste of time as, although most clinically significant "cold" auto-antibodies are high titre, this is by no means a universal n, and so, if you ignore an antibody because it is low titre, you could be in trouble (more to the point, your patient could be in trouble).  Secondly, determining the specificity of the antibody is even more of a waste of time.  If it is an auto-anti-I, are you going to give adult ii blood?  No.  If it is an auto-anti-H, are you going to give O_h blood? No.  If it is an auto-anti-HI are you going to give blood from a donor who is O_hAND an adult ii?  Well, if you can find such a donor anywhere in the world, you are a better serologist than anyone who has yet existed.  Is the thermal amplitude useful?  You bet your bottom dollar it is!  The human body will never reach 4^oC or 22^oC, so performing tests at those temperatures is a waste of time, BUT, the extremities (fingers, toes ears, nose, etc) can go down as far as 30^oC., and this is why Petz and Garratty recommend that tests are performed STRICTLY at 30^oC, as, if the antibody reacts at 30^oC or above, it is clinically significant as an auto-antibody.  Tests at 37^oC are only really useful if you are cross-matching blood for the patient, in order to see if there are any clinically significant alloantibodies present in the plasma.

On ‎6‎/‎22‎/‎2018 at 4:02 PM, Malcolm Needs said:

Well, if you follow Petz and Garratty, the "bible" of auto-immune haemolytic anaemias, first of all performing a titre is a total waste of time as, although most clinically significant "cold" auto-antibodies are high titre, this is by no means a universal n, and so, if you ignore an antibody because it is low titre, you could be in trouble (more to the point, your patient could be in trouble).  Secondly, determining the specificity of the antibody is even more of a waste of time.  If it is an auto-anti-I, are you going to give adult ii blood?  No.  If it is an auto-anti-H, are you going to give O_h blood? No.  If it is an auto-anti-HI are you going to give blood from a donor who is O_hAND an adult ii?  Well, if you can find such a donor anywhere in the world, you are a better serologist than anyone who has yet existed.  Is the thermal amplitude useful?  You bet your bottom dollar it is!  The human body will never reach 4^oC or 22^oC, so performing tests at those temperatures is a waste of time, BUT, the extremities (fingers, toes ears, nose, etc) can go down as far as 30^oC., and this is why Petz and Garratty recommend that tests are performed STRICTLY at 30^oC, as, if the antibody reacts at 30^oC or above, it is clinically significant as an auto-antibody.  Tests at 37^oC are only really useful if you are cross-matching blood for the patient, in order to see if there are any clinically significant alloantibodies present in the plasma.

Hi Malcom, not withstanding the reference given, if there is indeed any contradiction, but I had a co-worker who practiced Blood Bank at a hospital where part of their type an screen practice was a 4C incubation for all open heart pre surgical patients. The idea being that the docs wanted to be aware of any cold agglutinins because during the surgery, and as a consequence of the proceedings, the patient's body temp would drop. To what degree, and how it compares to the referenced recommendation you site I do not know. I hope that retirement is treating you well and best wishes, Ronald. 

Thanks Malcom

On ‎6‎/‎23‎/‎2018 at 4:15 PM, rravkin@aol.com said:

I had a co-worker who practiced Blood Bank at a hospital where part of their type an screen practice was a 4C incubation for all open heart pre surgical patients. The idea being that the docs wanted to be aware of any cold agglutinins because during the surgery, and as a consequence of the proceedings, the patient's body temp would drop. To what degree, and how it compares to the referenced recommendation you site I do not know.

We used to use that same procedure when we were doing open heart surgeries and the patient was on bypass. If our antibody screen was positive at 4 degrees, we would test at 10, 15, and 20 degrees - maybe even 30 degrees if the room temperature incubation was positive.  Whatever the thermal range was, we would then do an antibody ID (who cares) and titer at that temperature.  We would also include a test at 4 degrees using a 20% suspension of the patient cells to see if there was agglutination after 30 minutes.  We in the blood bank were very happy when new surgeons were brought in who no longer wanted that testing -- working on beating hearts and doing mini valve replacements, etc. has helped us immensely.

4 hours ago, TreeMoss said:

We used to use that same procedure when we were doing open heart surgeries and the patient was on bypass. If our antibody screen was positive at 4 degrees, we would test at 10, 15, and 20 degrees - maybe even 30 degrees if the room temperature incubation was positive.  Whatever the thermal range was, we would then do an antibody ID (who cares) and titer at that temperature.  We would also include a test at 4 degrees using a 20% suspension of the patient cells to see if there was agglutination after 30 minutes.  We in the blood bank were very happy when new surgeons were brought in who no longer wanted that testing -- working on beating hearts and doing mini valve replacements, etc. has helped us immensely.

Hi TreeMoss, I gather that you and your crew were not real inspired by this line of testing. When the practice was first explained to me it seemed like a good practice, the idea being that if the patient had a cold reacting antibody and needed transfusion during the procedure when their body temp was less than normal, perhaps the OR staff would be better prepared in treating any adversities. I guess that your new surgeons do not agree with this practice. But can I ask what kind of incubators were used in your blood bank to test at 10, 15, and 20C? The reason for my question is that I have only done cold incubations at BB Room Temp and 1-6C BB Refrig temp.

Perhaps I'm a little naive, but I find some of the "old time" logic somewhat illogical. I appreciate that a unit of red cells being transfused would potentially be "cold" - 1 - 6 C at the start of infusion, i.e., might cause a cold-agglutinin issue, but almost immediately, the infused portion would equilibrate to the temperature of the circulating blood. Additionally, the unit itself would start to warm-up to room temperature.

Certainly additional problems could arise from "by-pass" procedures, but are the devices\pumps "cold" - 1 - 6 C ?? I suspect they operate at room temperature, nowhere close to refrigerator temperatures.

After all that rambling, I meant to say that I don't why anyone would test "cold autoantibodies" at temperatures below that of typical (surgical) rooms. However, I'm sure there is a a whole library of circumstantial, anecdotal evidence supporting such extreme testing protocols.

I am also of the opinion that the "cold" antibodies discussed here are insignificant in virtually all cases (except as an artifact to get rid of when antibody screening!). 

Occasionally we will see an order for cryoglobulins--which may be a problem at RT during pump by-pass procedures.

Scott

Hi Scott and Exlimey, perhaps the idea of a hemolytic reaction is remote when considering cold agglutinins but if the patients body temp and OR temp are below normal body temp and room temp respectively, and, if the cold agglutinin is strong enough, either by way of concentration therein of bonding strength, does the cold agglutinin not have the capability of causing rbc agglutinins to form and remain stable long enough to cause damage to the microvasculature in the same manner as with Lupis Erythmatosis.?

10 hours ago, rravkin@aol.com said:

Hi Scott and Exlimey, perhaps the idea of a hemolytic reaction is remote when considering cold agglutinins but if the patients body temp and OR temp are below normal body temp and room temp respectively, and, if the cold agglutinin is strong enough, either by way of concentration therein of bonding strength, does the cold agglutinin not have the capability of causing rbc agglutinins to form and remain stable long enough to cause damage to the microvasculature in the same manner as with Lupis Erythmatosis.?

That is exactly the theoretical risk that concerns the medical staff, but in my non-medical, laboratory-based opinion, the risk is extremely low. Extreme testing protocols (below 30 C) for cold-agglutinins are rarely informative, often having very specious clinical relevance. Does anyone really know what the results mean ? How high must a titration be to be significant ? If you look hard enough, you can find cold-reactive autoantibodies in most people, hence why routine testing protocols now deliberately avoid test phases below 37 C. Modern, super-sensitive test systems (PEG-IAT, CAT) don't even allow tests below 37 C and openly admit that IgM antibodies may not be detected (typically the form that "colds" take). Even with these "deficiencies" they still are licensed/approved for antibody detection and ID.

If a patient is in such a dire situation that they're undergoing radical surgery, with the selective use of hypothermia and/or by-pass procedures, the least of their worries is a cold agglutinin.

The easy fix to the transfusion of "cold blood" is a blood warmer, but obviously this would be contraindicated during hypothermic processes.

On ‎6‎/‎26‎/‎2018 at 7:07 PM, rravkin@aol.com said:

But can I ask what kind of incubators were used in your blood bank to test at 10, 15, and 20C? The reason for my question is that I have only done cold incubations at BB Room Temp and 1-6C BB Refrig temp.

We simply used a beaker with water and ice and maintained the temperature during the 15 minute incubation period. 

This procedure was brought to us by a perfusionist who had been an MLS prior to becoming a perfusionist.  She developed these procedures as part of a project when she was in perfusionist school.

On ‎6‎/‎27‎/‎2018 at 5:16 AM, exlimey said:

Perhaps I'm a little naive, but I find some of the "old time" logic somewhat illogical. I appreciate that a unit of red cells being transfused would potentially be "cold" - 1 - 6 C at the start of infusion, i.e., might cause a cold-agglutinin issue, but almost immediately, the infused portion would equilibrate to the temperature of the circulating blood. Additionally, the unit itself would start to warm-up to room temperature.

Certainly additional problems could arise from "by-pass" procedures, but are the devices\pumps "cold" - 1 - 6 C ?? I suspect they operate at room temperature, nowhere close to refrigerator temperatures.

After all that rambling, I meant to say that I don't why anyone would test "cold autoantibodies" at temperatures below that of typical (surgical) rooms. However, I'm sure there is a a whole library of circumstantial, anecdotal evidence supporting such extreme testing protocols.

The physicians would use cold cardioplegic solution -- 4 degrees - when putting the patient on bypass.

13 hours ago, exlimey said:

That is exactly the theoretical risk that concerns the medical staff, but in my non-medical, laboratory-based opinion, the risk is extremely low. Extreme testing protocols (below 30 C) for cold-agglutinins are rarely informative, often having very specious clinical relevance. Does anyone really know what the results mean ? How high must a titration be to be significant ? If you look hard enough, you can find cold-reactive autoantibodies in most people, hence why routine testing protocols now deliberately avoid test phases below 37 C. Modern, super-sensitive test systems (PEG-IAT, CAT) don't even allow tests below 37 C and openly admit that IgM antibodies may not be detected (typically the form that "colds" take). Even with these "deficiencies" they still are licensed/approved for antibody detection and ID.

If a patient is in such a dire situation that they're undergoing radical surgery, with the selective use of hypothermia and/or by-pass procedures, the least of their worries is a cold agglutinin.

The easy fix to the transfusion of "cold blood" is a blood warmer, but obviously this would be contraindicated during hypothermic processes.

Hey Exlimey, very well put. 

15 hours ago, TreeMoss said:

The physicians would use cold cardioplegic solution -- 4 degrees - when putting the patient on bypass.

Wow. Thank you for that information. That certainly could influence the concern some of the medics demonstrate. Is the surgical room also chilled ?

7 hours ago, exlimey said:

Is the surgical room also chilled ?

They usually are, so I'm sure that is the case in heart surgeries, as well.

On ‎6‎/‎29‎/‎2018 at 2:38 PM, TreeMoss said:

They usually are, so I'm sure that is the case in heart surgeries, as well.

So Treemoss, do you know if rbc agglutination, and the damage it can do to the microvasculature,  is a concern with this surgical patient group if a cold antibody is demonstrating?

On ‎7‎/‎2‎/‎2018 at 3:56 PM, rravkin@aol.com said:

So Treemoss, do you know if rbc agglutination, and the damage it can do to the microvasculature,  is a concern with this surgical patient group if a cold antibody is demonstrating?

I'm sure that would only be in cases where the patient was cooled down.  I'm sure there have been times when a blood warmer was used in surgery just as it can be on the floors.

On ‎7‎/‎16‎/‎2018 at 4:16 PM, TreeMoss said:

I'm sure that would only be in cases where the patient was cooled down.  I'm sure there have been times when a blood warmer was used in surgery just as it can be on the floors.

Thank you TreeMoss but I was asking about Open Heart Surgical patients where their body temp would be lowered and as such some surgeons request a cold Ab screen be performed as part of the blood bank pre-surgical  work up. If a blood warmer were used the cooler blood from a cooler surgical suite would course through a blood warmer and into a cooler then normal body, thus lowering the temp of the now transfused blood. Therefore, even if a blood warmer were used for this patient would a cold reacting antibody still be of some concern with respect to the minimal possibility of agglutination of these transfused rbc's?

On ‎8‎/‎1‎/‎2018 at 6:17 PM, rravkin@aol.com said:

I was asking about Open Heart Surgical patients ... would a cold reacting antibody still be of some concern with respect to the minimal possibility of agglutination of these transfused rbc's?

I would suspect so -- if agglutination is happening at lower temperatures in a test tube, I would expect the agglutination to be occurring in the cooled down patient.