Transfusion for a group A2B with anti-A1 sickle cell disease patient

[Malcolm Needs ☆]

On 11/07/2017 at 3:46 PM, Neil Blumberg said:

In general we do our best to not detect antibodies that do not react at 37 degrees and IAT, but obviously reverse grouping is performed at room temperature, so you are occasionally going to find an anti-A1.  We would probably not ignore this, despite the evidence that clinically evident hemolysis is very unlikely to nil.  Our approach would probably be washed group O red cells.  The reasoning is to minimize the infusion of incompatible soluble antigen and antibody from the ABO blood group.  It may well be overkill in this setting, but we are now convinced that the use of so-called universal donor group O red cells and group AB plasma is likely harming some patients by increasing bleeding, multi-organ failure and infection through an immune complex/hemolysis mechanism. 

Traditionally, hematologists and transfusion professionals are only worried about massive hemolysis.  Recent work by many groups suggests that low levels of hemolysis (say 10-50 mg/dl) are not benign. Free hemoglobin, heme and iron are clearly not benign in animal models.  We know from experiments of nature such as sickle cell anemia and paroxysmal noctural hemoglobinuria that these sorts of "invisible" levels of hemolysis likely cause vasculopathy, platelet activation and thrombosis and predispose to nosocomial infection.  Hence we are trying to never give transfusions that may contribute to hemolysis by infusing incompatible ABO antibody or soluble/cellular antigen.  Hence the saline washing of group O red cells in some instances in order to avoid both antibody as well as antigen incompatibility.  We have randomized trial data that this approach is safe (no excess bleeding) and reduces inflammation in cardiac surgery and improves survival in acute myeloid leukemia.  Moreover use of ABO identical and washed (and leukoreduced) transfusions almost completely abrogates the last platelet refractoriness seen in patients with hematologic malignancy.  Yes it's extra work and costs a bit more, but HLA matched platelets are expensive too :).

Finally, since converting to this policy of ABO identical everything for all recipients we have seen our febrile and allergic transfusion rates decrease substantially, and our red cell alloimmunization rates to CcEe and K have decreased by 50% or so.  We consider this good news.

 

One reason patients with sickle cell anemia have such high alloimmunization rates, we suspect, is the tendency to use group O red cells (unwashed) which creates low levels of ABO immune complexes in non-O recipients that predispose to immune activation.  No data on this, just suspicion and extrapolation from our clinical data.

Whilst I have no doubt that your findings are valid Neil, and, having not read your findings, it is difficult (if not impossible) to argue with what you say with any degree of certainty (certainly no scientific certainty), I do find it difficult to accept the need for expensive washed group O red cells, resuspended in AB plasma, in such a situation (particularly as any manipulation of a unit of red cells, and/or plasma, is a situation where a bacterial [and/or viral, fungal and/or parasitic] contamination may be introduced, however asceptic the technique used may have proved in the past.  Surely, in a situation where anti-A₁, not detected by standard serological techniques, blood found to be compatible by an IAT cross-match at 37^oC is efficacious?  One only has to look at the published evidence (such as that quoted in Reid ME, Lomas-Francis C, Olsson ML.  The Blood Group Antigen FactsBook.  2012, 3^rd edition, Academic Press) to see that an anti-A₁, not detected by standard serological techniques is not clinically significant.

In addition, there is evidence that transfused donor red cells take on the Lewis type of the recipient (Sneath JS, Sneath PHA.  Transformation of the Lewis groups of human red cells.  Nature, Lond, 1955; 176: 172.  doi 10.1038/176172a0) and that red cells, in the situation of a minor ABO-mismatch bone marrow transplantation, also take up the ABO type of the recipient (Needs ME, McCarthy  DM, Barratt J.  ABH and Lewis antigen and antibody expression after bone marrow transplantation.  Acta Haematologica 1987; 78: 13-16.  doi 10.1159/00020582B); this latter paper was very much a theory at the time of publication, rather than proven fact.

Recently, however, a paper has been published (Hult AK, Dykes JH, Storry JR, Olsson ML.  A and B antigen levels acquired by group O donor=derived erythrocytes following ABO-non-identical transfusion of minor ABO-incompatible haematopoietic stem cell transplantation.  Transfusion Medicine 2017;  27 : 181-191.  doi: 10/1111/tme.12411), that suggests that even transfused red cells, including washed group O red cells, rapidly take up ABO antigens from the plasma, when the recipient is an A and/or B secretor positive recipient, and to a lesser extent, transfused washed group O red cells, more slowly, but "speed" and secretor status notwithstanding, still take up ABO (or, as I should really write, ABH) antigens from the plasma, and possibly even from "host" red cells to transfused red cells.

All of this theory suggests that, at worst, there may be a little destruction of A₁ red cells, when transfused to an A₂ individual, when there is an anti-A₁ present that is not detected at 37^oC by standard serological techniques, but that, given only a certain percentage of donor red cells survive for an acceptable time frame, A₁ red cells transfused to an A₂ individual, where an anti-A₁, not detected by standard serological techniques, are quite acceptable, and. more to the point, efficacious.

[Yanxia]

12 hours ago, Malcolm Needs said:

 

All of this theory suggests that, at worst, there may be a little destruction of A₁ red cells, when transfused to an A₂ individual, when there is an anti-A₁ present that is not detected at 37^oC by standard serological techniques, but that, given only a certain percentage of donor red cells survive for an acceptable time frame, A₁ red cells transfused to an A₂ individual, where an anti-A₁, not detected by standard serological techniques, are quite acceptable, and. more to the point, efficacious.

Sir, do you mean the anti-A1 in the A2 individual will destruct the transfused A1 cells where the circulation temperature is lower than 37^oc, even the anti-A1 has no reaction at  37^oc

[Malcolm Needs ☆]

1 hour ago, yan xia said:

Sir, do you mean the anti-A1 in the A2 individual will destruct the transfused A1 cells where the circulation temperature is lower than 37^oc, even the anti-A1 has no reaction at  37^oc

No, not as such.  It is just that a certain number of the red cells contained in the unit of blood will be close to the end of their life anyway, and so will be destroyed by apoptosis.  An anti-A₁ that does not react at strictly 37^oC will not accelerate this process.

[Neil Blumberg]

"I do find it difficult to accept the need for expensive washed group O red cells, resuspended in AB plasma, in such a situation (particularly as any manipulation of a unit of red cells, and/or plasma, is a situation where a bacterial [and/or viral, fungal and/or parasitic] contamination may be introduced, however asceptic the technique used may have proved in the past.  Surely, in a situation where anti-A₁, not detected by standard serological techniques, blood found to be compatible by an IAT cross-match at 37^oC is efficacious?"

 

We don't use AB plasma as universal donor unless the blood type of the recipient is unknown.  We believe giving AB plasma to group O individuals in large amounts probably increases morbidity and mortality through an immune complex mechanism (see reference below).

 

I agree that anti-A1 not reactive at 37 degrees and/or IAT can be safely ignored.  anti-A1 reactive at 37 degrees or IAT probably should be honored by full crossmatch compatible group A red cells, or, if essential with washed group O red cells.  At least, that is our approach.

[Neil Blumberg]

Vox Sang. 2009 May;96(4):316-23. doi: 10.1111/j.1423-0410.2009.01167.x. Epub 2009 Feb 24.

Post-transfusion mortality among recipients of ABO-compatible but non-identical plasma.

Shanwell A¹, Andersson TM, Rostgaard K, Edgren G, Hjalgrim H, Norda R, Melbye M, Nyrén O, Reilly M.

Author information

 

Abstract

BACKGROUND AND OBJECTIVES:

The consequences of ABO-compatible non-identical plasma for patient outcome have not been studied in randomized clinical trials or large cohort studies and use varies widely in the absence of evidence-based policies. We investigated if transfusion with compatible instead of identical plasma confers any short-term survival disadvantage on the recipients.

MATERIALS AND METHODS:

The cohort of all 86 082 Swedish patients who received their first plasma transfusion between 1990 and 2002 was followed for 14 days and the risk of death in patients exposed to compatible non-identical plasma compared to recipients of only identical plasma.

RESULTS:

After adjustment for potential confounding factors, there was an increased mortality associated with exposure to ABO-compatible non-identical plasma, with the excess risk mostly confined to those receiving 5 or more units (relative risk, 1.15; 95% confidence interval, 1.02-1.29). Stratification by blood group indicated higher risks in group O recipients, especially when the compatible plasma was from a group AB donor.

CONCLUSIONS:

This study suggests that ABO-compatible non-identical plasma is less safe than identical plasma. Subanalyses by blood group suggest a role for circulating immune complexes. Our findings may have policy implications for improving transfusion safety.