Neil Blumberg

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.

"the presenter stated specifically that NOTHING has been grandfathered. " I think the presenter is mistaken. The FDA specifically noted that the area of rare reagents and cells, and similar testing would not be subject to LDT enforcement. Of course, all the opinions in the world matter not a bit until the FDA actually acts or does not act. I cannot imagine they want to be inspecting every tertiary care hospital and blood center reference laboratory for this purpose. And most of the things we are discussing in the transfusion service and immunohematology lab are not used to provide diagnostic results to practitioners, but rather used for internal resolution of therapeutic decisions. Quite different from your average laboratory test which provides quantitative or semi-quantitative result to physicians and other practitioners who make decisions based upon lab results. Perhaps a nuance, but a real difference. If the FDA insists we validate the use of a potent anti-HPA1 anti-platelet antibody in our decision making, we're out of luck :). Ain't happening. Interestingly, much of what we do in clinical medicine has not been "validated" or subjected to FDA-like regulation. Such as using autologous or allogeneic stem cell transplants, liver transplants, using a stethoscope or looking at a patient's retina with an ophthalmoscope. No validation. No data to speak of at all.

I think most blood bank reagents and tests have been grandparented in. The FDA knows there is no alternative to these home brew reagents and testing procdures.

There are no data to answer your questions, as far as I know. It's important to make sure that the fetal cell quantitation is not measuring maternal cells with increased fetal hemoglobin, as this would overestimate the RhIgG dose needed. This is not a problem with some methods (anti-Rh(D) quantitation of fetal cells but can be a problem with acid elution (K-B) staining, for examples. If there is convincing evidence these are fetal cells, give the correct dose IV even if many vials. IM injections are cruel and unusual punishment if IV injectables are available. For patients who are not planning future pregnancies, this should be discussed with the patient. For sick patients who have received transfusions, we do not infuse RhIgG except for younger women (<40-50) who plan future pregnancies and have a prognosis for survival. Hemolysis from RhIgG can be a problem at high doses of RhIgG and large transfusion volumes. On balance we usually elect not to give RhIgG to women who have received entire or multiple units of Rh(D) positive red cells. It's a complex clinical decision with little science to guide us.

We do not use enzyme treated cells when trying to detect or work up cold agglutinins. No reason to enhance their reactivity in vitro. If they are not detectable by routine LISS at body temperature or antiglobulin methods they are not of clinical importance.

Another inspector who is a bureaucratic and clinically ignorant rigid thinker. My sympathies. There is no reason to document early infusion rates, and these vary by patient due to clinical condition. This is just a guideline and not a requirement, as the inspector would know if they had any bedside clinical practice experience. Just say it's a rough guideline, not a requirement, and clinical judgement will determine the infusion rate for each patient.

If the antibody does not react at 37 or antiglobulin phase, we would not recommend a blood warmer. Agree that in patients with cold agglutinin disease or hemolysis after exposure to cold, would use a warmer. Remember that our techniques in the lab routinely detect antibodies of no clinical significance. For one thing, we never centrifuge patients at 170g to enhance binding of red cells to antibody :). So on balance, unless you have an antibody of known clinical significance historically (antibodies in the Rh, Kell, Duffy, Kidd, S, etc. systems) and it reacts at body temperature, it's probably not significant. Cold antibodies of wide thermal range may be significant but usually not if they don't react at body temperature in vitro.

As you know a difficult question. The use of group O blood for non-O patients should be limited as soon as the ABO type is known, and ABO type specific given. There are some old admonitions to never transfuse type specific after X numbers of group O red cells or whole blood. This is nonsense, so do not follow this old precept. Give only ABO type specific as soon as possible. As for giving non-O blood to O patients when all other options are exhausted, I would only do this if death were imminent due to bleeding, not ever for routine transfusion. There are case reports of no hemolysis in such situations, including the one below from my original mentors from half a century ago. Accidental error but no consequences. But giving non-O blood to O recipients has the potential to cause rapid death in many instances. We don't know why there are such varied responses. Case Reports Transfusion . 1975 Nov-Dec;15(6):577-82. doi: 10.1046/j.1537-2995.1975.15676082233.x. Unusual response to ABO incompatible blood transfusion D H Buchholz, J R Bove PMID: 1198685 DOI: 10.1046/j.1537-2995.1975.15676082233.x Abstract Three units of group A blood were inadvertently administered to a group O recipient during surgery without evidence of hemoglobinemia, hemoglobinuria, hypotension, disseminated intravascular coagulation, acute renal tubular necrosis, or other signs and symptoms of transfusion reaction. The recipient had normal concentrations of IgG, IgA, and IgM as well as complement (C3) prior to transfusion and anti-A agglutinins titered to 64 (titer of 128 by the antiglobulin technic). Seventeen hours following the transfusion, 28 per cent of the circulating red blood cells were group A (equivalent to 475 ml of packed cells); they were eliminated by day 5 without evidence of hemoglobinuria, hemoglobinemia or hyperbilirubinemia. Anti-A titers (antiglobulin) had risen from a posttransfusion low of 4 to 4,096 by day 10. After treatment of serum with 2-mercaptoethanol, however, hemolytic activity which was first noted on day 5 was lost and the antiglobulin titer dropped to 24 which suggested that most of the anti-A produced in response to the transfusion was IgM rather than IgG. The anti-A titer had dropped to essentialyy pretransfusion levels and the majority of anti-A present was IgM by day 91. The recipient suffered no untoward effects from the transfusion and was in good health three months following the transfusion.