Neil Blumberg

Transfusion Medicine in our institution includes the Blood Bank/Transfusion Service, Donor Service and Stem Cell Processing Laboratory. Outside each facility we have the relevant signage. Some places it includes Therapeutic Apheresis, which in our institution is both physically separate (so is our Donor Room) and located in the Dept. of Medicine (Cancer Center). As long as the facilities are well defined, I'm not sure the overall name matters much, except on stationery, which no one uses much anyway :).

No AABB standard requires a crash cart. Donors do not develop anaphylactic reactions, but this type of reaction is why offices or facilities that administer transfusions or IVIgG (and similar products) need to be able to administer epinephrine emergently. Most of the rest of the stuff in a crash cart would never be needed and certainly not for blood donors. So no crash cart unless you are administering human blood products or drugs that can cause anaphylaxis.

"Just curious, can one give a group A1 kidney to a group B patient who has a very low isoagglutinin titer ?" It's been done. Depends on the ability to suppress the anti-A titer low enough through immunosuppressive drugs and plasma exchange, the usual preparative regimen. Obviously ABO identical is best, but this is an alternative at some centers with experience doing these transplants.

"The bottom line was, if the treating physician wanted to use up the entire inventory trying to save a life, we could not deny them the blood, even though it places other patients at risk. " I would call this some combination of cowardice and insanity, speaking purely personally. Taking responsibility for difficult decisions is why physicians get paid well, and avoiding decision making is irresponsible.

We are inspected by FDA, NY State, AABB, CAP and FACT. Lots of opportunities for self-important, obsessive folks to make useless work for the people trying to take care of patients. The stories I could tell. We've also had many rational, balanced, thoughtful inspectors who clearly are only focused on the important stuff, to be fair. But a significant portion of our profession(s)' people do not realize that getting staff to focus on minutiae that will not affect patient outcomes distracts staff from doing the important things well. A well known psychologic/cognitive fact. Keep it simple and avoid worrying about unimportant stuff. The notion that documentation is more important than anything else is the most pernicious piece of rubbish in medicine, and driven by the administrative/legal model (and billing of course). And people proudly spout this nonsense as if it actually helped anyone but those in accounts receivable. I'd personally like the technologist doing my pre-transfusion testing to get the ABO and antibody screen correct as a trillion fold more important relative to them documenting what time, date or temperature all of that was done. Not to mention what that person had for lunch or dinner before the crossmatch (coming soon to an inspection near you). For the record I'm a Gemini, which I assiduously and loyally document in every interpretation and progress note I write.

Just the person you want operating on your brain or reading your prostate biopsy, no doubt. Makes one proud to be a part of the same profession. Not. Pettifogging fool. Perhaps he is nice to his dog and children.

I am waiting for some conscientious, firm inspector to insist we add the blood bank director's hat size and astrological sign to each procedure. About as relevant to health care as most of the stuff the accreditation and regulatory agencies obsess about.

There are no data suggesting a particular limit. Survival is very unusual after 30-50 units of red cells, but everyone has exceptional cases like those mentioned above. We have discussed futility of care many times, and our practitioners are quite amenable and forthcoming. We have stopped resuscitation in a young man having a liver transplant go badly, when there was no surgical path to hemostasis after about 250 units, but this is unusual too. Bottom line, a case by case decision as to whether care is futile and/or the patient's needs endanger the well being of other patients needing transfusion. Those are the key issues in each case to my way of thinking.

Another bureaucratic authoritarian idiocy? Sorry, couldn't restrain myself, but there is a cadre of "quality gurus" who are constantly thinking up irrelevant, pointless make work stuff for the rest of us. This is how civilizations come to an end. Why in the world would an SOP have to have the address, name, GPS co-ordinates, topographic elevation and postal code of the facility? How does that address any patient care issue in the universe?

I can see why they make this recommendation. But it is wrong if one has the ability to be sure that the ABO type is known without doubt (the discrepancy has been resolved by drawing another sample and repeating the front typing, for example). We have become quite casual in assuming group O red cells are safe as "universal donor." While this is safest when the ABO is not known, we should never forget this is sub-optimal for non-O patients. Any therapy that has significantly greater risk than the preferred therapy (ABO type specific/identical) is sub-optimal, and we seem to have forgotten this due to the logistic convenience (and sometimes necessity) to give group O red cells to non-O patients. It can be fatal not to mention impairing the blood supply. The absence of isoagglutinins, if anything, makes transfusion safer. The use of universal group O red cells in an emergency may make clinical sense, but exposes the patient to potentially fatal (if very rare) hemolysis due to few dozen milliliters of incompatible plasma when transfused to the 55% of patients who are not group O. To my knowledge, I have never seen or read about a patient whose front typing led to an ABO hemolytic reaction because it was "wrong." The front typing is immunohematologic gold and clinically critical. Not so much the back typing which is merely confirmatory. Granted that in the absence of technical and medical expertise it may not be possible to execute my suggestions, but we should be aware that following the AABB Standards advice is inferior clinical care if implemented as an absolute, because on occasion it will cause great harm.

"No full blood type means you should be giving type O red cells and type AB plasma, which no one wants to do unless warranted! " The AABB standards, if that's what they say, are totally wrong from a clinical perspective and shear bureaucratic rigidity. If you know the patient's ABO type with total certainty from the front type, the correct and safest transfusions are ABO identical red cells, platelets, plasma and cryo. We never transfuse antigen positive cells, obviously, in the face of even weak anti-A or anti-B. But when things are clear and there is no antibody present, ABO identical is the clear clinical imperative. I always put the patient's best interest before regulatory or accreditation bad advice, and as a physician, that is both my responsibility and authority. Happy to defend this approach in public, court or any other venue :).

"Again, the issue at play is that we cannot confirm the patient ABO and the ABO is not clear at initial testing. We understand that weak positive is positive but the issue is having no reaction at all. You cannot confirm type with discrepancy present." My point is that if the front type is unambiguous and also reproducible on the same sample and on a repeat sample, the back type is almost totally irrelevant clinically. It's a useful check on the front type, but not indispensable for determining the ABO type. As a tertiary care children's hospital we treat infants, children and occasional adults with no detectable isoagglutinins all the time, and we simply rely on the front type for transfusion, if necessary. Thus far, no problems in my 42 years here. If there is any uncertainty, we use washed group O red cells, which are not available at most hospitals. Unfortunately the entire field of blood banking/transfusion medicine labor under the convenient but incorrect belief that stored supernatant of red cells and platelets, particularly ABO mismatched, causes no harm to patients. Randomized trials suggest otherwise. If it were up to me, every hospital would be required have the capability of removing supernatant from red cells and platelets in select patients.

Instead of fooling around with the back type why not consider doing an anti-globulin crossmatch, or confirming the ABO type of the unit and the patient? There is no clinical reason to have a stronger backtype if the patient's ABO is clear on repeat samples. If it is considered important for non-clinical reasons, perhaps do an antiglobulin backtype rather than just arbitrarily increasing the serum to cells ratio, which makes sense but is hard to validate in any convenient way. Patients with agammaglobulinemia, whether congenital or acquired, may have no isoagglutinins to detect, and it's not worth getting obsessive about it in my view. Here's another way of looking at this. The absence of isoagglutinins actually makes transfusion safer, as an ABO hemolytic transfusion reaction is very unlikely to occur if there are no detectable anti-A/anti-B.

Let me ask the basic question is this necessary? If the weak back type agrees with the front type, you know everything you need to safely transfuse the patient. Why bother with serologic make work? It has no clinical relevance that I can think of.

Agreed. We don't use the ADCC, we just give M negative. Even a little, sub-clinical hemolysis probably isn't good for patients :).

As a general rule, an anti-M that doesn't react with heterozygous cells probably isn't very biologically potent or clinically relevant, so that's my take on that issue. We honor anti-M antibodies that react at 37 or antiglobulin phase, but many of these probably would not cause significant hemolysis in all likelihood.

Some of the platelet and endothelial injury and impaired hemostasis after ABO mismatched transfusions may be due to our transfusion practices of routinely using ABO non-identical transfusions. This involves infusing ABO incompatible cellular (platelet) and soluble (plasma, cryo) antigen and antibody (group O red cells and whole blood). These antibodies and immune complexes have been modeled in vitro and interfere with endothelial integrity, platelet function, thrombin generation, and are pro-inflammatory. When a greater effort is made to avoid ABO non-identical transfusions, mortality per unit of red cells transfused drops by 30% and mortality in cardiac surgery is decreased by 75%. Refaai MA, Fialkow LB, Heal JM, Henrichs KF, Spinelli SL, Phipps RP, Masel E, Smith BH, Corsetti JP, Francis CW, Bankey PE, Blumberg N. An association of ABO non-identical platelet and cryoprecipitate transfusions with altered red cell transfusion needs in surgical patients. Vox Sang. 2011 Jul;101(1):55-60. doi: 10.1111/j.1423-0410.2010.01464.x. Epub 2011 Mar 18. PMID: 21414009; PMCID: PMC3115402. McRae HL, Millar MW, Slavin SA, Blumberg N, Rahman A, Refaai MA. Essential Role of Rho-Associated Kinase in ABO Immune Complex-Mediated Endothelial Barrier Disruption. Biomedicines. 2021 Dec 7;9(12):1851. doi: 10.3390/biomedicines9121851. PMID: 34944667; PMCID: PMC8698390. Refaai MA, Carter J, Henrichs KF, Davidson DC, Pollock SJ, Casey AE, Spinelli SL, Phipps RP, Francis CW, Blumberg N. Alterations of platelet function and clot formation kinetics after in vitro exposure to anti-A and -B. Transfusion. 2013 Feb;53(2):382-93. doi: 10.1111/j.1537-2995.2012.03718.x. Epub 2012 May 25. PMID: 22624532; PMCID: PMC3566315. Refaai MA, Cahill C, Masel D, Schmidt AE, Heal JM, Kirkley SA, Blumberg N. Is It Time to Reconsider the Concepts of "Universal Donor" and "ABO Compatible" Transfusions? Anesth Analg. 2018 Jun;126(6):2135-2138. doi: 10.1213/ANE.0000000000002600. PMID: 29099432. Blumberg N, Heal JM, Hicks GL Jr, Risher WH. Association of ABO-mismatched platelet transfusions with morbidity and mortality in cardiac surgery. Transfusion. 2001 Jun;41(6):790-3. doi: 10.1046/j.1537-2995.2001.41060790.x. PMID: 11399821. Malvik N, Leon J, Schlueter AJ, Wu C, Knudson CM. ABO-incompatible platelets are associated with increased transfusion reaction rates. Transfusion. 2020 Feb;60(2):285-293. doi: 10.1111/trf.15655. Epub 2020 Jan 8. PMID: 31912889; PMCID: PMC7769037. Magid-Bernstein J, Beaman CB, Carvalho-Poyraz F, Boehme A, Hod EA, Francis RO, Elkind MSV, Agarwal S, Park S, Claassen J, Connolly ES, Roh D. Impacts of ABO-incompatible platelet transfusions on platelet recovery and outcomes after intracerebral hemorrhage. Blood. 2021 May 13;137(19):2699-2703. doi: 10.1182/blood.2020008381. PMID: 33649761; PMCID: PMC9635530. Inaba K, Branco BC, Rhee P, Holcomb JB, Blackbourne LH, Shulman I, Nelson J, Demetriades D. Impact of ABO-identical vs ABO-compatible nonidentical plasma transfusion in trauma patients. Arch Surg. 2010 Sep;145(9):899-906. doi: 10.1001/archsurg.2010.175. PMID: 20855762. Shanwell A, Andersson TM, Rostgaard K, Edgren G, Hjalgrim H, Norda R, Melbye M, Nyrén O, Reilly M. Post-transfusion mortality among recipients of ABO-compatible but non-identical plasma. Vox Sang. 2009 May;96(4):316-23. doi: 10.1111/j.1423-0410.2009.01167.x. Epub 2009 Feb 24. PMID: 19254234.

"I am still wondering if there is really so much difference of transfusing equal volume of mismatched RBCs vs. plasma/platelets." There's some truth to this. The notion of universal donor red cells (group O) and plasma (group AB) turns out to be more of a relative thing than a virtue. Group O red cells have 20-40 ml of donor plasma that is incompatible with 55% of recipients (groups A, B and AB, obviously). This is usually not a huge problem, but when given in large amounts or from a high titer donor, hemolysis and organ failure can occur, including death. When group AB plasma is given to groups O, A and B recipients, there is soluble antigen incompatible with all of these patients and observational studies show an increase in sepsis, organ failure (particularly lung) and death. Thus we need to emphasize avoiding infusion of ABO incompatible antibody, cellular and soluble antigen. This can be accomplished by giving ABO identical or washed group O cells and ABO identical plasma. Platelets are a particular problem since inventory is limited. ABO identical is best. When ABO minor mismatched (group O platelets to a non-O patient) are transfused, the hemolytic transfusion reaction rate is about 1 in 700. Of course, we may be missing harm to donor endothelial cells, for one thing, since they carry ABO antigens. When ABO major mismatched platelets are administered (e.g., group A to a group O recipient) the increase in mortality/bleeding is about 20%, so harm to at least 1 in 5 patients. We need to stop doing this.

When the major hematology and transfusion medicine textbooks acknowledge the data showing that ABO mismatched transfusions don't provide hemostasis, actually increase bleeding, and increase platelet transfusion refractoriness, then hematologists will change their approach. Probably some time before the heat death of the universe. Instead, one major textbook quotes methodologically unsound data from a study that classified platelet transfusions as ABO identical based upon the first transfusion, even if large numbers of ABO mismatched transfusions were subsequently given to that patient. Total scientific nonsense. No doubt medical education is also to blame. I've been here 42+ years and haven't been invited to give a single talk to medical students about transfusions for many years (this is changing in 2023). The curriculum bears little resemblance to what physicians need to know, unfortunately. Highly dysfunctional when the single most frequently performed inpatient procedure, transfusion, doesn't have a major role in the curriculum. Ah well.

I realize this is "fighting city hall" but is there a more useless requirement than having everyone review and sign off on procedures that haven't changed one iota? In our laboratory, this is many hundreds of procedures (including the one on how to write a a procedure :). Bureaucratic make work of no value whatever. An unfortunate example of the administrative/legal mindset versus the scientific/clinical mindset in our society. Probably an early small sign of the coming end of our civilization when non-productive work receives such priority. Seriously.

Short answer would be any ABO type if a one time thing, along with a prayer card for no hemolysis or post-transfusion purpura. You could make a case for type A as the anti-B is likely to be lower titer, lower biologic activity than the anti-A in group O platelets (unless low titer) or group B platelets. But this is largely theoretical hand waving.

I should add the good news is that when one starts prioritizing ABO identical platelets over inventory management, one reduces the platelet transfusions needed by perhaps 50%. So our platelet shortages will disappear in large part if we stick with ABO identical as much as possible. See attached randomized trial from eons ago :). ABO identical reduces transfusion reactions as well, HLA and rbc alloimmunization. Not to mention decreasing bleeding and mortality. ABO randomized trial UR european j haematology 1993 copy.pdf ABO plt tx revisited cumulative effects.pdf Platelet transfusion worsens ICH Stroke 2020 copy.pdf

Another point. Since group O whole blood has proven as safe or even safer than typical component therapy (A platelets, A or AB plasma) in massive transfusion of trauma patients, perhaps group O low titer platelets would be safer than group A or B platelets for an AB patient :)? No one knows, but worth considering. The big problem is probably giving non-O platelets to O patients. There is evidence this increases bleeding and mortality. Just like red cells, only O platelets for O recipients is a good practice. The AB patient may be less of a problem, since giving some small amount of antibody may be less dangerous. A risk of hemolytic reaction of about 1 in 700 or so. The risk of mortality in transfusing an O patient with A platelets is probably 1 in 5 (see attached). ABO incompatible platelets intracranial bleeding 2021.pdf ABO plasma incompatible platelets and hemolytic reactions.pdf

"Since AB+ people are considered the "universal recipient" , we give them any type platelets, usually starting with the one with the closest out date. " I grant you that this is widely shared idea in our field for decades. It is also seriously wrong. It prioritizes inventory management over patient wellbeing. Our approach to ABO and platelets is distinctly different from ABO and red cells with no rational basis. Antibody and complement destroy red cells and platelets equally well. The only difference is that instead of free hemoglobin being released, it's mediators such as VEGF, IL-6 and other platelet pro-inflammatory, immunomodulatory and pro-thrombotic granule contents are released. ABO mismatched platelet transfusions at least double the refractoriness rate in repetitively transfused patients (see attached for references), and actually increase bleeding and mortality. The answer to the question is ABO identical is by far most effective and safest. If you have to give ABO mismatched, there is probably no good answer other than washed/volume depleted O's, A's or B's, where most of the incompatible plasma is removed. If that's not possible, postponing platelet transfusion until ABO identical is available when feasible, giving half doses of ABO identical if two patients need the one available unit, etc. are also reasonable. Sadly, ABO mismatched platelets are probably worse than no platelets at all. They provide little or no hemostatic benefit and increased risks of bleeding, organ injury and death for the patient. If I were the attending physician, I would generally give no platelets if ABO identical or washed O's weren't available in a stable, non-bleeding patient with a count of over 5,000. The good news is we can improve outcomes by just doing what we do for red cells. Do not transfuse ABO incompatible antigen or antibody. It's bad for red cells, platelets and endothelial cells, all of which have complement and Fc receptors that bind immune complexes, and all of which bear ABO antigens on their surfaces. Carr ABO mismatched refractoriness copy.pdf ABO story expanded.docx ABO endothelial cell paper.docx NEJMc2034764 copy.pdf NEJMc2034764_appendix copy.pdf

Hard to know what to do. Most weak D patients will not make antibodies to D epitopes. Most antibodies to D epitopes will not cause serious hemolysis. But we don't have enough clinical data to predict which patients will make antibodies and which antibodies will be dangerous after transfusion or cause hemolytic disease of the newborn. Hence we usually treat these patients as Rh positive for purposes of administering Rh immune globulin to the mother, and as Rh negative for transfusion purposes. Not a major public health problem, but challenging. Interestingly, automated gel technologies, and manual versions of these, often type patients as strongly Rh (D) positive when tube testing shows weaker reactions (2+ or less has semi-arbitrarily been chosen). So we will soon be finding whether these patients can make anti-D antibodies and whether these antibodies are clinically significant. My best guess is mostly not an issue. It does solve the Rh immune globulin question, since the baby is Rh positive and one administers RhIgG to Rh negative mothers.