Neil Blumberg

I think you do what is practical in your setting. There is no evidence one way or the other for prophylactic use of cold vs. room temp platelets in terms of actual bleeding prevention. Platelet count increments were the metric used, and we now know that platelet count is a relatively minor contributor to bleeding at counts much above 5-10,000/µl. So we're all operating based upon "expert" (often wrong) opinion, not actual data. In general, at platelet counts above 10,000/µl there is virtually no evidence of benefit for platelet transfusion and plenty of evidence of harm (particularly if not ABO identical). So the best clinical decision is often to postpone or eschew transfusion in my view. The long standing view that transfusion is almost always better than no transfusion is tragically wrong.

If the infusion center is part of the hospital and served by the hospital transfusion service, they do not need a separate FDA registration because they are not a transfusion service. The FDA does not regulate nor inspect infusion centers. They regulate and inspect transfusion services and blood banks. Provision of products to an infusion center would not require FDA registration per se. That is determined by what services you provide overall.

If the donor antibody screen is negative then the unit does not need to be labeled. Otherwise it does.

"Just to make sure I've understood, even if a patient just got their total plasma volume replaced with Group O albeit Low titer plasma, we should switch all products to their blood type the second we get a result?" Yes. Even after a one volume blood exchange 30-40% or more of the original red cells (recipient type) are still there, and more will be made during the recovery from anemia. So giving the patient's own red cell type is almost certainly better than infusing more anti-A and anti-B antibody via O red cells to A, B and AB patients. (I am also curious what you think of blood centers labeling red cells from antibody positive units as regular red cells and don't treat them as antibody positive units needing a minor crossmatch. The blood center claims that the Additive Solutions dilute the titer "enough." I admit I haven't looked for any research on this yet. I don't know if they titer the supernatant or what to prove this. I think this is irresponsible and scientifically indefensible, if I understand you. Also against FDA regs as the product is misbranded if the known antibody present is not identified on the label. The remark about additive solutions is totally without merit and once again, irresponsible. There are no data to support this approach. I don't want to be infusing anti-X antibody (that I don't know about) to a patient who might be X positive. Makes no sense and one would be crucified in a court of law.

Switch back to the patient's own ABO type as soon as possible is my advice. For everything. RBC, platelets, cryo, plasma. Worrying about the anti-A and anti-B in low titer whole blood is relevant, but so is the smaller amount of incompatible plasma in group O red cells, which are not low titer. There are rare reports of severe hemolytic reactions to group O red cells in non-O patients. Furthermore, the patient is continually making their own group A, B or AB red cells, so hesitancy about transfusing their own ABO type is not helping things get better. By giving additional group O products we are making the problem worse, not adding safety in any way. Furthermore, the non-O patient's endothelial cells, platelets, von Willebrand factor, hepatocytes, etc. are all incompatible with the transfused group O plasma, and their function is impaired when modeled in vitro, and leads to increased bleeding. Thus there is no benefit whatever in giving group O red cells (or whole blood for that matter) to non-O patients once the hemorrhagic problem is largely under control. And there is likely added risk. It is only adding harm and reducing the inventory of group O blood for group O recipients. A total mistake of the last few decades in my opinion. Giving group O plasma containing products to non-Os is only reasonable when you don't know the patient's blood group, or don't have their blood group in stock, or it's an emergency with no time for giving type specific. No one ever went broke overestimating the importance of the ABO blood group in transfusion. See attached for the literature references. ABO trauma commentary Frontiers bioengineering.pdf Reconsider ABO compatible:universal donor.pdf ABO ARC MAC copy.ppt

There is no evidence that cold stored platelets returned to room temperature need any change in outdating. I wouldn't go beyond 7 days for pathogen reduced platelets or 5 days for non-PRT platelets. Would just use clinical judgement. The reference above relates only to frozen platelets in any case, an entirely different critter, so not necessarily informative.

Just for the record, I am not aware of any data, nor can I conceive of a mechanism by which red cell transfusion would correct base excess. This patient apparently had an extensive and severe infection, so vasodilation due to septic shock seems a real possibility. Transfusing a patient to a hemoglobin of 14.6 is not something I've ever heard experts in anesthesiology and intensive care medicine advocate, and transfusion to this level would be expected to increase the risk of thrombosis greatly. And just for completeness, the diagnosis of septic shock in a patient with a recent serious infection and also likely receiving broad spectrum antibiotics does not require the presence of positive cultures for diagnosis. Hard to grow bugs in vitro when there are high concentrations of anti-microbials. This is why DNA tests are probably a better tool to diagnose infection in such patients, if available. Does not require growth, just the presence of bacterial nucleic acids.

Hemoglobin and hematocrit re-equilibrate over minutes to an hour. Usually minutes. Not five hours. That's not compatible with what we know. Transfusing a patient in this setting is more likely to cause inflammation, thrombosis, congestive heart failure, etc., than help, although it is understandable that the surgeon is trying to "do something" for a patient who is not responding to treatment. The hemoglobin may or may not be precise, but it tells you that the circulating red cell mass isn't likely the problem. If the patient is in shock and not bleeding, the problem is almost certainly not fixable by transfusion of red cells is my thought. But desperation leads people to try stuff that is unlikely to help and may, in some cases, harm. Likely cause(s) of the shock in such patients is cardiac dysfunction, sepsis or something else not easily fixable. Not due to anemia/lack of red cell mass obviously.

The standards probably don't apply to post-mortem transfusions. I cannot imagine why an organ harvest surgery would require transfusion at all, but I'm not a surgeon. I've had requests to transfuse platelets and plasma to organ donor patients, which we've uniformly denied. I'd need some explanation of why transfusion, which is pro-inflammatory, immunomodulatory and pro-thrombotic, would benefit the potential organ recipient. There is so much misinformation, partially promulgated by the transfusion medicine community, of the "benefits" of transfusion, that it is sometimes difficult to explain to clinicians why transfusion is a bad idea in many situations.

"only when delaying the blood to wait for a second sample would affect or delay patient care - some of our outpatient dialysis clinics or sister hospitals are counties away and that would not be good patient care." That is my point, more or less. Transfusing group O to non-Os in non-emergent situations is inferior patient care, contrary to long standing dogma. We don't know what damage is done, but there is almost certainly damage for some patients due to low level hemolysis and brisk hemolysis in rare patients. That's avoidable by giving ABO type specific. The administratively driven requirement for a second sample is the source of this inferior patient care. No thought was given to the possible consequences to patients from hemolysis when requiring O red cells for patients without a second type available. While rare patients got the wrong ABO type due to lack of a confirming specimen, every patient who isn't O who receives O red cells is at risk of hemolysis with rare exceptions. We don't know the consequences because it has never been studied, but it's likely much worse than we think.

The absence of a second sample leading to transfusing group O to everyone without a second sample is an example of why this practice is likely doing more harm than good in my view. Group O red cells are acceptable for all in an emergency, but they are potentially harmful to non-O recipients due to the presence of 20-30 ml, give or take, of incompatible plasma for A, B and AB patients. There are case reports of severe hemolytic reactions in this setting. Low level hemolysis that is not clinically evidence is present in some recipients and is associated with thrombosis, infection and organ injury in animal models. In experiments of nature such as sickle cell anemia/paroxysmal nocturnal hemoglinuria below visually apparent levels of free hemoglobin cause severe complications. Thus, contrary to long accepted practice, Group O is NOT universal donor, except in emergencies when the recipient's type is not known, or the patient's own ABO type red cells are unavailable and there is life threatening bleeding or anemia. The routine use of group O red cells for everyone in routine transfusion is an unfortunate practice that has arisen due to convenience and erroneous assumptions of equivalent safety. Not a good practice for patient safety.

PRP joint injections are not transfusions and thus not governed by FDA or other regulations for transfusion services. Furthermore, they are autologous. So there is no need for transfusion service involvement in any way shape or form. There are no AABB/CAP rules or regulations as this isn't a transfusion and does not involve the clinical lab.

We don't do a second draw for confirming potassiums or troponins either, which, absent transfusion, are much more important than ABOs for whatever reasons they are asking for them.

Agree that if not for transfusion purposes, ABO types do not need repeating. We don't do confirmations for potassiums or troponins either.

"So, you would continue to do IAT XMs for the rest of their life even if the patient's Lewis antibody is not detectable?" No, only if the antibody were detectable in the 37 degree/IAT antibody screen.

Lewis antibodies do not cause HDFN and do not need titration. We do not Lewis phenotype transfusions to patients with anti-Lewis antibodies, but do a manual antiglobulin crossmatch to find units that do not react. I'm sure there are rare patients whose antibodies can cause removal of Lewis positive red cells at an accelerated rate, but this is not something that needs to be considered unless the patient shows signs of hemolysis or rapid red cell removal. Never come across this in 50 years of practice :). But never say never in medicine.

Yes Normosol should be fine.

Yes. And worse, some cells react differently, including having no reactivity, as compared with cells of the same degree of zygosity. Thus the possibility of Kidd antibodies needs to be seriously considered when the recipient is negative for one or both antigens and the panel is reactive but without clearcut specificity for Jka or Jkb.

Forgot to add, Plasmalyte is also FDA approved for use with blood components. No data :). In our OR, there is no normal saline at all, just Ringer's Lactate and Plasmalyte, the latter used for blood component administration. Plasmalyte is slightly more expensive than normal saline, but also somewhat less toxic.

Transfus Apher Sci. 2023 Jun;62(3):103641. doi: 10.1016/j.transci.2023.103641. Epub 2023 Jan 13. Association of crystalloid fluid infusion with intravascular hemolysis and organ dysfunction in hematopoietic stem cell transplant patients Melissa R Holloway 1, Thomas Fountaine 2, Kelly Henrichs 3, Tate Feeney 4, Jeffrey Andolina 5, Kristen O'Dwyer 6, Jane Liesveld 7, Neil Blumberg 8, Eric Huselton 9 Affiliations expand PMID: 36653255 DOI: 10.1016/j.transci.2023.103641 Abstract Endothelial cell activation and injury is common after hematopoietic stem cell transplant (HSCT) and is associated with many post-transplant complications. An underexplored mechanism of endothelial cell damage in this population is the infusion of normal saline (NS, 0.9 % sodium chloride) and other crystalloids, as NS use is associated with adverse outcomes in other patient populations. We hypothesized that the infusion of unbalanced crystalloids during HSCT may lead to changes in biomarkers commonly associated with red blood cell (RBC) hemolysis in patients before and after infusion, and that markers of endothelial and end-organ damage during admission may be associated with markers of hemolysis and total crystalloid use. Samples were collected from 97 patients. From pre-fluid infusion to post-fluid infusion, mean haptoglobin decreased (11.7 ug/ml vs 8.4 ug/ml; p < 0.0001), hemopexin decreased (549 vs 512 μg/ml; p = 0.005), and red cell distribution width (RDW) decreased (15.7 vs 15.6; p = 0.0009). During admission (mean 19.4 days, SD 9.9), all markers of tissue and organ damage, including mean creatinine, lactate dehydrogenase (LDH), blood urea nitrogen (BUN), total bilirubin, AST, and ALT, increased from admission to peak levels (p < 0.0001). On linear regression, fluid volume (ml/kg) of crystalloid infusion positively predicted post-fluid infusion cell-free hemoglobin (r(96) = 0.34, p < 0.0001), free heme (r(96) = 0.36, p < 0.0001), and peak LDH during admission (r(75) = 0.23, p = 0.041), and negatively predicted post-fluid infusion hemopexin (r(96) = - 0.34, p < 0.0001). Unbalanced crystalloids may contribute to hemolysis and endothelial damage in HSCT patients. Alternatives such as buffered crystalloid solutions (PlasmaLyte, Lactated Ringer's) may be worth investigating in this population.

Saline review for TRASCI final[1].pdf

The preferred solution for administration of blood components should be Plasmalyte. Less hemolysis in vitro. Normal saline is toxic to patients and should never be used, in my opinion. Causes a metabolic acidosis and kidney injury. Ringer's lactate is fine too, but as you note, is forbidden (based upon no data whatever) by FDA. The only patients who might benefit from normal saline are those with a metabolic hypochloremic alkalosis, which is very rare. Our enthusiasm for normal saline was entirely misplaced. Randomized trials show it to be harmful and increase mortality in critically ill patients. Balanced Crystalloids versus Saline in Critically Ill Adults. Semler MW, Self WH, Rice TW.N Engl J Med. 2018 May 17;378(20):1951. doi: 10.1056/NEJMc1804294.PMID: 29768150 Free PMC article. BACKGROUND: Both balanced crystalloids and saline are used for intravenous fluid administration among critically ill adults. ...METHODS: In a pragmatic, cluster-randomized, multiple-crossover trial in five intensive care units at an academic center, we assigned 15,802 adul … Balanced Crystalloids versus Saline in Noncritically Ill Adults. Self WH, Semler MW, Wanderer JP, Wang L, Byrne DW, Collins SP, Slovis CM, Lindsell CJ, Ehrenfeld JM, Siew ED, Shaw AD, Bernard GR, Rice TW; SALT-ED Investigators.N Engl J Med. 2018 Mar 1;378(9):819-828. doi: 10.1056/NEJMoa1711586. Epub 2018 Feb 27.PMID: 29485926 Free PMC article. Clinical Trial. BACKGROUND: Comparative clinical effects of balanced crystalloids and saline are uncertain, particularly in noncritically ill patients cared for outside an intensive care unit (ICU). METHODS: We conducted a single-center, pragmatic, multiple-crossover trial comparing balan … Balanced Crystalloids versus Saline in Critically Ill Adults. Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, Stollings JL, Kumar AB, Hughes CG, Hernandez A, Guillamondegui OD, May AK, Weavind L, Casey JD, Siew ED, Shaw AD, Bernard GR, Rice TW; SMART Investigators and the Pragmatic Critical Care Research Group.N Engl J Med. 2018 Mar 1;378(9):829-839. doi: 10.1056/NEJMoa1711584. Epub 2018 Feb 27.PMID: 29485925 Free PMC article. Clinical Trial. BACKGROUND: Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes. METHODS: In a pragmatic, cluster-randomized, multiple-crossover trial conducted in five …

Your guess is as good as anyone else's. . I suspect the FDA will continue doing regulatory stuff until told to stop by Congress or some court. I'd assume they will regulate LDTs as they have proposed.

I just answered this question. My Score PASS  

I believe internal QC or non-patient testing is not covered by the FDA regs. Only tests used to report patient results.