Neil Blumberg

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.

No such accreditation or regulatory need for a separate room to my knowledge.

In general, based upon the randomized trials, don't even think about transfusing non-bleeding patients with adequate marrow function above 7 g/dl or hematocrit 21%. More harm than benefit. For premature newborns, different guidelines, and each neonatalogist has his or her own ideas. But the guidelines in the literature are way too high with no evidence of benefit, as for most transfusions these days. A moving target and often a controversial area with more dogma than data.

It's a state law issue. Each state sets its own regulations about who can order what, if I recall correctly. It sometimes may be an institutional issue.

If the baby is not anemic and has no evidence for hemolysis, I'd just leave it at that. There are variant plasma antigens that can elicit antibodies and these can be hard to identify using red cell serologic techniques. If the eluate is negative against panel red cells, this is high probability. Perhaps mom is sensitized to a paternal immunoglobulin variant and these immune complexes are adhering to red cells. There are no standardized tests for such anti-plasma protein antigens, to my knowledge. Not very satisfying, but the clinical findings are the most important issues here, not the serologic issues.

We offer RhIgG to Rh negative patients who are female and <50 years old who receive Rh pos products, whether plasma or platelets.

Those are theoretical constructs. The data suggest fresh isn't best if there are more infections as there have been in randomized trials of fresh vs. average storage period. More study needed, but the data are more important than the dogma. Infection is the most common cause of morbidity and mortality in all hospital patients, including newborns.

Sickle trait cells do not sickle under physiologic conditions compatible with life. Purely a theoretical construct. Oxygen transport is also normal under physiologic conditions compatible with life. The evidence that sickle trait cells present any risks to any patient through transfusion is exactly zero. Patients with sickle trait rarely, if ever, have any problems attributable to sickle trait. The epidemiologic evidence is likewise weak, if not zero.

There is reason NOT to use the freshest possible units. They may be more toxic than intermediate stored units. This is something that made sense but was almost certainly wrong. See below for the reasoning and published data. We use <21 days as fresh for this reason and avoid <7 days storage for everyone based upon the randomized trial data. BMJ 2019;366:l4968 doi: 10.1136/bmj.l4968 (Published 5 August 2019) Page 1 of 1 Letters Trivella and colleagues present some caveats around the subject of duration of red cell storage and clinical outcomes.1 Studies have been widely interpreted as showing that transfusion is not associated with adverse clinical outcomes. I think this is a serious misinterpretation of the data. In addition to the concerns raised by the authors, another valid hypothesis, which has received little attention, is that very short storage red cells might be more dangerous than medium storage periods (say 7-21 days) and equally dangerous as longer storage red cells (say 28-42 days). An inverted U shaped curve. The evidence for this comes from a meta-analysis finding that “ultra short” storage of red cells was associated with a post-transfusion increase in nosocomial infection.2 Shorter storage red cells have a greater imbalance of oxidation-reduction potential than longer storage red cells in preliminary studies in vitro.3 Red cell storage duration is also a poor predictor of post-transfusion free haemoglobin and heme, putative mediators of toxicity from transfusions.4 5 We need better metrics for predicting red cell transfusion efficacy and toxicity. The simple expedient of fresher red cells is clearly not that metric and might be leading us to transfuse more toxic red cells (very fresh) in the most fragile patients, such as premature newborns. A new approach is clearly called for by the current data. At our centre we define fresh as <21 days of storage, and we generally never transfuse a red cell that has been stored for much less than 7-10 days, for the above reasons as well as logistics of supply. Competing interests: None declared. 1 Trivella M, Stanworth SJ, Brunskill S, Dutton P, Altman DG. Can we be certain that storage duration of transfused red blood cells does not affect patient outcomes?BMJ 2019;365:l2320. 10.1136/bmj.l2320 31186250 2 Alexander PE, Barty R, Fei Y, etal . Transfusion of fresher vs older red blood cells in hospitalized patients: a systematic review and meta-analysis. Blood 2016;127:400-10. 10.1182/blood-2015-09-670950 26626995 3 Schmidt A, Gore E, Cholette JM, etal . Oxidation reduction potential (ORP) is predictive of complications following cardiac surgery in pediatric patients[abstract]. Transfusion 2016;56(Supplement S4):20A-1A. 4 Cholette JM, Pietropaoli AP, Henrichs KF, etal . Elevated free hemoglobin and decreased haptoglobin levels are associated with adverse clinical outcomes, unfavorable physiologic measures, and altered inflammatory markers in pediatric cardiac surgery patients. Transfusion 2018;58:1631-9. 10.1111/trf.14601 29603246 5 Pietropaoli AP, Henrichs KF, Cholette JM, etal . Total plasma heme concentration increases after red blood cell transfusion and predicts mortality in critically ill medical patients. Transfusion 2019;59:2007-15. 10.1111/trf.15218 30811035 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/ permissions LETTERS

If the unit if leukoreduced, as all red cell transfusions should be, there is no need for CMV negative in my view.

This is a clinical call that we make between the senior medical technical staff present and the attending physician. We routinely switch male patients, and older females who are Rh negative to Rh positive red cells when transfusion rate is significant and supply constrained. No policy. Just a clinical decision, which we communicate to the treating team. Typically a liver transplant that has gone badly, an exsanguinating trauma patient and similar situations.

We use either ABO identical or washed O red cells. Usually volume reduced so the hematocrit is around 70-80% either by centrifugation or washing with Plasmalyte. We have data that saline washing is likely associated with more hemolysis and metabolic acidosis. Leukoreduced and <21 days old. We prefer not to use the very short storage red cells (<7 days) as there is evidence they are more dangerous from randomized trials, albeit in mostly adult patients. We do not CMV test or test for hemoglobin S, except for exchange transfusions. No evidence that hemoglobin S trait is a problem for transfusion in any situation, but particularly for smaller volume transfusions. We do irradiate for newborns since immunodeficiencies, while very rare, are often not diagnosed until later in infancy or early childhood.

In New York State, we also are inspected by the state. FDA, NY State, AABB, CAP. You can make a sound argument that this is wasteful and duplicative. Obviously we don't have any choice about FDA and NY State. CAP and AABB, as accreditation organizations, will accept the results of each other's inspections, which is a plus, but you are still dealing with two sets of requirements. My advice to smaller facilities is to pick one if you can do so, and not duplicate your efforts and expense. Both organizations are essentially trade organizations, not scholarly/research societies. They both provide important educational opportunities, but you don't need both to keep your staff current, in my view. With the shortage of medical technologists, reducing non-productive non-clinical effort is a priority to prevent staff burnout and keep everyone focused on the main mission, patient care.

Amen to the comments above. 28% is pretty good. About 5% of our patients have antibodies detectable in the indirect antiglobulin test, so we'd rather receive more samples rather than fewer.

If there is detectable anti-D in the antibody screen, would usually transfuse Rh negative blood, although the risk of clinically significant hemolysis is low. We do not know that mild hemolysis is benign, for one thing. As for "freshness" this turns out to be one of the things we got totally wrong. Fresher blood (<7 days say) is probably less safe for reasons unknown than blood stored 7-21 days. Fresher blood is associated with increased infections in the recipient in randomized trials, so our approach to this in our center has turned 180 degrees. We prefer not to use <7 day old red cells, but define fresh as 7-21 days. Randomized trial data. Thus in your situation I would strongly prefer 7-21 day old Rh negative red cells to giving <7 or <5 or whatever Rh positive red cells to a child with anti-D from Rh IgG. Freshness is harmful nonsense with a long history of expert opinion that, regrettably has been proven wrong by data.

Bottom line is believe the lab test results (data) and make clinical decisions weighing the risks and benefits :). A patient who has anti-K (mimicking, auto, passive, or otherwise) should receive K negative red cells.

The observation that antigen negative cells can yield an eluate with an antibody for an antigen not present has been known for more than half a century I believe. It's often referred to as the Matuhasi-Ogata phenomenon, first reported in the 1950s and 1960s. My mentor, Joe Bove and Patrick Mollison wrote about this a bit later in the 1970s based upon work Bove did during a sabbatical in London. Needless to say, I heard about this often as a resident physician under Bove's supervision :). Brings back memories.... Immunology,1973,25,793. Non-specificBindingofIgGtoAntibody-coated RedCells (The'Matuhasi-OgataPhenomenon') J.R.BOVE,*A.M.HOLBURNANDP.L.MOLLISON MRCExperimentalHaematologyUnit, StMary'sHospitalMedicalSchool,LondonW21PG Summary.Severalobservershavereportedthatredcellscoatedwithaspecific blood-groupantibodymaytakeupasecondblood-groupantibodynon-specifically, aneffectknownasthe'Matuhasi-Ogataphenomenon'.Inthepresentwork, thiseffectwasinvestigatedusingeither'25I-labelledantibodiesofvarious specificitiesora1311-labelledpreparationofIgGlackingrelevantantibodies.In confirmationofmuchpreviouswork,itwasfoundthatredcellstookupappreciableamountsofIgGnon-specifically;however,thisuptakewasnotincreased bypreviouscoatingoftheredcellswithspecificantibody.WhentheIgGtakenup non-specificallyincludedablood-groupantibodyinrelativelyhighconcentration, aneluatesubsequentlypreparedfromtheredcellscontainedsufficientoftheantibodytobedetectable.Thus,thefindingofunexpectedantibodiesineluatesmay beduetonon-specificuptakeofIgGratherthantoadherenceofantibodiesto antigen-antibodycomplexes.

Why would you want to transfuse blood at such a high rate? Perhaps I'm misunderstanding, but I would never transfuse a patient who wasn't exsanguinating at 300 ml/min. And having that level of flow isn't necessary for transfusion, so I'm a bit clueless about why you picked that number. It's a dialysis issue, not a transfusion issue, no? Vascular access is not the transfusion service's purview, in general, so I'm not clear why you are concerned. Have you had lots of red cells returned because they didn't have vascular access?

Thanks Malcolm. One issue with a very long life is that few are left who remember you. Larry was a remarkable and important contributor to progress in transfusion medicine, particularly on the subject of autoimmune hemolytic anemias, along with his long time collaborator, the late George Garratty. I remember both of them well and wish peace to their family and friends.

All potentially clinically significant antibodies like this can be managed pretty well by non-invasive fetal monitoring for anemia by ultrasound (doppler velocity), so the management should be the same for all such antibodies. Clinical variation is great, as you all know, so the drill is to monitor the fetus. No anemia, no worries. Anemia leads to intervention. Serology is largely irrelevant (e.g., titers) but habit is to measure them by most clinicians.

It is true that group O patients are more likely to bleed if injured or on anticoagulants. Not something easily adjusted for, but many O patients (they are 45% or so of the patients in NYC) received ABO identical platelets and did not bleed or have increased mortality. When we switched to ABO identical platelets, cryo (and plasma) for all, our mortality rate per red cell transfused in surgical patients went down by about 15% or so. Transfusing ABO major incompatible red cells is bad for patients. The same apparently holds true for platelets. What is surprising is that it took us this long to realize that transfusing incompatible cellular antigen is bad for patients, whether those cells are red cells or platelets. Soluble incompatible antigen (e.g., AB plasma to group O patients) as mentioned above, also seems to be bad for patients as well. Animal models of immune effects of administering incompatible antigen support these observations. In vitro models show that immune complexes of ABO antigen and antibody interfere with endothelial cell integrity, clot formation, platelet function and stimulate inflammation, which worsens bleeding and organ function.