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Neil Blumberg

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Everything posted by Neil Blumberg

  1. TACO is congestive heart failure. Hypertension is not congestive heart failure, but may be of concern. Transient rises in the range of 170 to 200 that last minutes, not hours, are usually not of concern. That can happen with rapidly climbing a flight of stairs.
  2. Most CMV infections are acquired through environmental exposure, including breastfeeding from and close contact with a CMV infected mother. The likely source of the infection in question was exposure to family members, not transfusion. That's why close to 80% of adults in some populations are CMV seropositive. The virus is ubiquitous and highly infectious, but rarely causes any serious clinical effects except in utero and in severely immunocompromised patients.
  3. There remains controversy about this, but we have been using leukoreduction as our only method of CMV risk reduction for close to 30 years, with no reported cases of CMV transmission. We have a 70 bed newborn intensive care unit, do about 180 stem cell transplants (about 40% allogeneic), and do the occasional intrauterine exchange transfusion. CMV serotesting is never necessary for donor blood in my opinion. The existing literature isn't entirely definitive but studies have not shown that combining leukoreduction and CMV serotesting has much, if any clinical benefit. Both observational series and randomized trials demonstrate that CMV transmission after leukoreduction is not any more common than after CMV serotesting. Indeed, most CMV transmissions are likely due to seronegative donors who have recently acquired virus, but are still seronegative, or at least that's one theory. Bottom line, if you are 100% leukoreduced there is no need for CMV serotesting.
  4. In my 40 years of practice since finishing training we have never ordered Lewis negative units for transfusion. We give crossmatch compatible (IgG/37 degrees) units, although even that is probably overkill. Lewis antibodies do not cause hemolytic transfusion reactions with IgG/37 degree non-reactive units. Your pathologist is perhaps not a full time transfusion medicine physician? Not that there's anything wrong with that :).
  5. Because of the rare risk of a fatal hemolytic reaction, we only use washed group O red cells for our premature newborns. For other newborns and readmits we use ABO identical unless there is detectable maternal anti-A and/or anti-B, in which case we again use washed group O's. There is about 20-40 ml of residual plasma in almost all red cell units, more than enough to cause severe hemolysis in rare instances. We should not ignore that risk for our own convenience/inventory management/etc. in my view. We only transfuse unwashed group O red cells to patients of unknown ABO type in emergencies. There is additional evidence that ABO non-identical transfusions of incompatible antibody or soluble antigen causes harm to patients, in addition to the rare risk of life-threatening hemolysis. We have published a summary of this evidence. Is It Time to Reconsider the Concepts of "Universal Donor" and "ABO Compatible" Transfusions? Refaai MA, Cahill C, Masel D, Schmidt AE, Heal JM, Kirkley SA, Blumberg N. Anesth Analg. 2018 Jun;126(6):2135-2138. doi: 10.1213/ANE.0000000000002600.
  6. Sorry about the incomplete references. Here are the full references for the two missing :). ABO identical and washed blood transfusions as candidate strategies to reduce early mortality in acute promyelocytic leukemia. Sahai T, Henrichs K, Refaai M, Heal JM, Kirkley SA, Schmidt AE, Mendler JH, Masel D, Liesveld J, Aquina C, Blumberg N. Leuk Res. 2017 Nov;62:1-3. doi: 10.1016/j.leukres.2017.09.011. ABO-immune complex formation and impact on platelet function, red cell structural integrity and haemostasis: an in vitro model of ABO non-identical transfusion. Zaffuto BJ, Conley GW, Connolly GC, Henrichs KF, Francis CW, Heal JM, Blumberg N, Refaai MA. Vox Sang. 2016 Apr;110(3):219-26. doi: 10.1111/vox.12354.
  7. Transfusion of ABO-mismatched platelets leads to early platelet refractoriness. Carr R, Hutton JL, Jenkins JA, Lucas GF, Amphlett NW. Br J Haematol. 1990 Jul;75(3):408-13. The role of ABO matching in platelet transfusion. Heal JM, Rowe JM, McMican A, Masel D, Finke C, Blumberg N. Eur J Haematol. 1993 Feb;50(2):110-7. ABO and platelet transfusion revisited. Heal JM, Rowe JM, Blumberg N. Ann Hematol. 1993 Jun;66(6):309-14. Association of ABO-mismatched platelet transfusions with morbidity and mortality in cardiac surgery. Blumberg N, Heal JM, Hicks GL Jr, Risher WH. Transfusion. 2001 Jun;41(6):790-3. ABO identical and washed blood transfusions as candidate strategies to reduce early mortality in acute promyelocytic leukemia. Sahai T, Henrichs K, Refaai M, Heal JM, Kirkley SA, Schmidt AE, Mendler JH, Masel D, Liesveld J, Aquina C, Blumberg N. ABO-immune complex formation and impact on platelet function, red cell structural integrity and haemostasis: an in vitro model of ABO non-identical transfusion. Zaffuto BJ, Conley GW, Connolly GC, Henrichs KF, Francis CW, Heal JM, Blumberg N, Refaai MA. An association of ABO non-identical platelet and cryoprecipitate transfusions with altered red cell transfusion needs in surgical patients. Refaai MA, Fialkow LB, Heal JM, Henrichs KF, Spinelli SL, Phipps RP, Masel E, Smith BH, Corsetti JP, Francis CW, Bankey PE, Blumberg N. Vox Sang. 2011 Jul;101(1):55-60. doi: 10.1111/j.1423-0410.2010.01464.x. Providing ABO-identical platelets and cryoprecipitate to (almost) all patients: approach, logistics, and associated decreases in transfusion reaction and red blood cell alloimmunization incidence. Henrichs KF, Howk N, Masel DS, Thayer M, Refaai MA, Kirkley SA, Heal JM, Blumberg N. Transfusion. 2012 Mar;52(3):635-40. Is It Time to Reconsider the Concepts of "Universal Donor" and "ABO Compatible" Transfusions? Refaai MA, Cahill C, Masel D, Schmidt AE, Heal JM, Kirkley SA, Blumberg N. Anesth Analg. 2018 Jun;126(6):2135-2138.
  8. Both Plasma-Lyte A and Normosol are FDA approved in addition to saline. They are almost certainly better for the patient. The circular of information and AABB guidances need to be changed to reflect this old information (FDA label approval) and new information (normal saline is more toxic than other crystalloids--see the early March 2018 issue of NEJM for example; first authors Semler and Self, respectively).
  9. I agree that discussing the risks with the ordering provider is essential. Most physicians have zero formal training about transfusion risk. Medical school students today receive at most one lecture on transfusion, the most commonly coded procedure for inpatients in the USA. The medical curriculum is a political muddle where there is almost no relationship between what needs to be learned and what is taught. That said, every uncrossmatched blood order (with no ABO typing, no antibody screen) should be questioned, if possible. But signing a form isn't the key step :). A brief, to the point discussion of the risks of the giving ABO non-identical blood components, and in the absence of an antibody screen should be had if time permits. Clinicians, whether physicians, nurses, NPs, PAs, etc. often have no idea that these emergency transfusions are substantially less safe than waiting 20-30 minutes for ABO type specific, antibody screen vetted red cells.
  10. If anyone wants references to read supporting the above rant, I'm happy to post them. Or just go PubMed and search on Blumberg ABO platelets. I'm afraid on this issue, the academic medical community is pretty much doing the ostrich thing :). They are waiting for definitive proof when the evidence is already more than enough to change practices. The cavalier practice of using group O red cells as universal donor, equivalent to ABO identical, and AB plasma, in routine (as opposed to emergency) use should be stopped.
  11. There are multiple problems here that have not been adequately addressed by either the bedside practitioners and by the blood bankers/transfusion medicine community. The problems relate to assumptions that have turned out to be false. The first assumption is that platelet transfusion is very effective at treating or preventing bleeding. It turns out that's not really true, at least as currently practiced. Randomized trials show that, for example, in autologous stem cell transplant patients, prophylactic transfusion provides minimal benefit. In acute myeloid leukemia induction therapy (really sick patients with active disease), prophylactic transfusion provides some benefit. But at great cost to the patient. The more platelet transfusions you receive, the less likely you are to have your disease cured in our cohort study. So more conservative transfusion practice is actually a good idea. There is also no big rush. Waiting a few hours to receive a prophylactic transfusion of platelets is of no real concern in my view. Unless there is active bleeding, or a history of bleeding at certain counts, waiting for an ABO identical platelet makes great sense. It turns out that ABO mismatched platelets may not actually work to prevent bleeding and we have evidence they may actually make bleeding worse. In addition, platelet transfusion predispose to nosocomial infection, thrombosis and multi-organ failure in observational studies. And mortality. Clinicians should think six times before giving a platelet transfusion in many settings. The risks are vastly worse than we knew. As for us. We've vastly misread the efficacy and safety of platelet transfusions that are ABO mismatched. In our surgical cohorts, the more ABO mismatched transfusions you receive, the higher the mortality rate, as well as increased bleeding. The problem with titers is that antibody quantity is only one of the factors that influence biologic activity and clinical outcomes. Ability to fix complement, avidity, etc. are probably as important. There is absolutely no evidence for the common sense and likely partially true assumption that lower titer is safer. But what titer? Some places use 1:200 and some 1:50. No evidence. I'd obviously go with 1:50 before 1:200. But the real answer is ABO identical, even if waiting a few hours is necessary, or platelets stored without plasma (then group O would be best) or supernatant removal by washing. I'm sure Terumo or Haemonetics could come with a simple, fast, automated washing system (it probably won't be free ) if they thought people would buy them. They should and we should. Our current practices are probably doing minimal good, great harm and are not consistent with what we now know about ABO mismatched platelet transfusions. Hope this helps explain my passion on the subjects.
  12. To my knowledge there is not a shred of evidence that titers (or titres:)) have any clinical benefit in this situation. We are treating ourselves, not the patient. I understand the need to "do something." In our case, our something is always giving ABO identical platelets, or, when this is not possible, we wash group O platelets. Titer/titre then becomes a moot point. I also get that blood bankers hate to wash anything, especially platelets, but we have randomized trial data this improves survival in younger patients with leukemia. Also avoids positive DATs, hemolysis and refractoriness to transfusion. A culture change is needed in which we accept what we've know for decades. Transfusing a group O red cell (or platelet) to a non-O patient can very rarely result in fatal hemolysis. Why we keep doing this despite the ability to avoid this rare fatal complication is a mystery to me, except for inertia and inconvenience. Of course a long standing practice that we assumed completely safe without a shred of data is hard to change. But the evidence is quite clear that group O platelets and rbc are not universal donor unless you accept a small but real risk of death for the patient. Not a practice to be defended in this day and age. As hard as it will be, I hope we will all start doing that which is best for recipients. Not what is best for inventory control or reducing wastage, which are important but lesser values.
  13. I agree that somewhere the responsible transfusion service physician should have signed the SOP, or if the SOP could not be followed, signed a deviation report. Where I part company from the conventional way of doing things at some centers is asking that the ordering physician also sign an additional form confirming what is hopefully in the medical record, that this was an urgent situation where standard serologic testing could not be performed. Adding more bureaucracy in this way is obstructive, time wasting and energy sapping, and serves no clinical purpose in my view.
  14. This use of a signature as a bludgeon against ordering physicians is something we should give up. We all know that in most cases of life-threatening bleeding, even 5-10 minutes delay can be fatal, so why pretend that our testing is the key element in good care? We are partners in providing the appropriate care that the clinical situation calls for. If a physician says he or she cannot wait for testing (ABO/Rh, or antibody screen, or physical crossmatch) it makes no sense to contest that claim or ask them to document it with a signature putting all the responsibility for outcomes on their shoulders. Physicians give verbal orders for all sorts of things, and documenting that verbal order for blood transfusion prior to whatever testing is missing should include the verbal order. Signatures are a waste of everyone's time and an attempt to shift responsibility for outcomes for what we have to do onto the ordering provider. Your mileage may vary, but I thought we were a team.
  15. This is a controversial subject. Firstly, ABO identical is by the most effective and safest. ABO mismatched platelets are associated in randomized trials with a 2-5 fold increase in refractoriness to transfusion, with is in itself associated with early mortality. ABO mismatched platelets in observational studies are associated with increases in febrile transfusion reactions, allergic transfusion reactions, increased bleeding and mortality. Is a single transfusion likely to be lethal? Probably not, but the blithe use of any old ABO type for multiple transfusions is highly likely to cause morbidity and mortality. In a pinch, when the ABO is not known or ABO identical aren't available, washed or plasma reduced group O platelets are probably safest. If not available, group A is probably safest. My last choice in all instances would be plasma replete group O, because there is a tiny but real risk of a fatal ABO hemolytic reaction due to the 250 ml of incompatible plasma. Incompatible antigen is probably less risky, hence the recommendation of group A platelets. Group A plasma has anti-B, which is the least dangerous of the two isoagglutinins in every respect. Is It Time to Reconsider the Concepts of "Universal Donor" and "ABO Compatible" Transfusions? Refaai MA, Cahill C, Masel D, Schmidt AE, Heal JM, Kirkley SA, Blumberg N. Anesth Analg. 2018 Jun;126(6):2135-2138. doi: 10.1213/ANE.0000000000002600.
  16. The whole blood being used in Pittsburgh is leukoreduced. They have chosen a titer of 50, which I would think is much safer than 200, but who knows? It would nice to have high quality data, or any data whatever, comparing the results with whole blood with similar patients transfused with the usual group O red cells, platelets of whatever group (usually) and AB plasma. I'd speculate that there is no difference because mixing group O red cells with AB plasma gives patients a substantial dose of iatrogenic ABO immune complexes, which we have demonstrated leads to impaired platelet function (in vitro), endothelial damage (unpublished in vitro data) and increased bleeding (observational clinical data). Thus low titer group O whole blood might well be safer than our current practices, which have only been validated not to cause acute massive hemolysis, which is only one of many disastrous clinical outcomes that can result from crossing ABO barriers. Focusing on red cells is fine, but there are other cells in the body that carry ABO antigens (endothelial cells for example) and loads of soluble antigen.
  17. "Stupid question - why is group O whole blood better than group O pack cells and group A thawed plasma? " Not stupid at all. There is no clinical evidence that it is superior or inferior. In fact, no clinical evidence whatever. The main attraction is that it simplifies transfusion in the patients who require red cells, plasma and platelets. One bag instead of three. That it provides better hemostasis is a supposition that may or may not prove to be wrong. It's concerning to me that it's very hard to predict who really needs anything but red cells. One estimate from London is 25% but that includes everyone with an elevated PT/INR and PTT, which are not good tests for predicting bleeding. We examined the last half year of our ED uncrossmatched blood cooler release in our Level 1 trauma center in a medium sized American city. We do not routinely start the massive transfusion protocol with the first cooler (or even the second, unless asked to do so). Of the 230 or so patients, only 2 wound up using more than 8 red cells (0.86%). I suspect this is typical of many university hospitals and almost all smaller teaching hospitals. Hence, no whole blood, no massive transfusion protocol routinely started on arrival, unless requested. I would think that whole blood as the first product to be infused for our patients would harm more patients than help (TRALI, TACO, etc.).
  18. Probably not helpful, but there is not a shred of scientific or clinical evidence for the efficacy and safety of this time limit. Totally expert opinion based upon a group of white haired males (like me) sitting around a table eating tuna fish sandwiches 60 years ago :). We document such stuff for the two regulatory agencies and two accreditation groups we are inspected by. How's that for efficiency? Four inspections.
  19. Not to my knowledge. Indeed, I don't believe free standing EDs should have blood available, unless there is no hospital within 20-30 miles and no helicopters are available for transport. I would want patients with life threatening bleeding or anemia to be taken only to a facility with on-site surgical facilities, surgeons, interventional radiology, etc. which are generally not available in free standing EDs. In other words, a fully staffed hospital. I would advocate taking such critically ill patients to the nearest level 1 or 2 trauma center, whenever one can, and bypass the free standing ED.
  20. "How many techs work in your Blood Bank on a daily basis?" Typically 9-10 on days, 6-7 on evenings and 3-4 on nights, with fewer on holidays and weekend shifts. All are full-time transfusion service only licensed medical technologists. Also 5 supervisory level staff (3 of whom also work at the bench), 2 full-time education/reference specialists, 2 full-time stem cell processing. "How do you keep up with washing units during a surgery? Or do you wash units before the surgery?" We don't. We wash in advance if need be, and if that isn't enough, we do the best we can. Thanks to the fact that manufacturers have focused on apheresis devices and the 2991 and ACP-215 are much older technology, we do not have a closed system. In any case, storing washed red cells for more than a few days would defeat the purpose of removing the supernatant containing free hemoglobin, red cell microparticles, etc. "If they do not use the units, what can you do with them? What is your RBC/PLT unit loss rate (washed but not used?)?" We transfuse 20,000 red cells per year so finding a patient who needs an O or A red cell isn't difficult. Same for platelets. On a typical weekday we transfused 80-100 red cells and 10-20 platelet doses. Essentially no losses. Our platelet outdate rate is consistently about 1-3%, washed or otherwise. Usually these are for scheduled elective transfusions on both inpatients and outpatients. As blood bankers/transfusion service personnel we do many inconvenient things, some quite expensive (CMV serotesting--unnecessary and less clinically valuable than leukoreduction), antigen matching for patients with hemoglobinopathies (quite clinically effective but time consuming and expensive), use of apheresis platelets instead of whole blood platelets (an almost totally unnecessary misuse of donor resources in most cases, additional risk to donors, no clinical advantage of substance, and fabulously expensive). I'd gladly give up apheresis platelets (except for HLA matched) and their cost for universal leukoreduction in the USA and selective washing of ABO minor-incompatible platelets and red cells. The latter on rare occasions kills patients, yet we do nothing about it in most transfusion services, and routinely give group O platelets to non-O recipients. I know these dilemmas are easily ignored and scoffed at, but the facts support these unpopular contentions. I should add that we see perhaps 3-5 platelet transfusion refractory patients per year out of thousands of platelet transfusion recipients. This is a benefit of transfusing only ABO identical platelets and red cells (or washed O's) which our group and Robert Carr of the UK demonstrated 25-30 years ago reduces refractoriness by 2-5 fold in the only randomized trials that exist. We have randomized trial evidence that washed red cells and platelets also contribute to improved long term survival in acute myeloid leukemia patients and reduce inflammation in pediatric cardiac surgery patients. Arguing against washing because it's expensive (it's not really all that expensive compared with apheresis platelets), it's inconvenient (it sure is) andis not "essential" doesn't justify subjecting patients to inferior treatment approaches in our view. Obviously these approaches have not caught on in most places (ABO identical and selective washing) but it's not for lack of data :). Similarly, in our view, transfusing ABO mismatched platelets for our own convenience, inventory purposes and to save outdating does not make sense when there is abundant evidence that this practice seriously harms some patients. Hence, plasma removal by washing when indicated and feasible. Contrary to 75 years or more of practice and tradition, there is no such thing as "universal donor group O red cells" and "universal donor group AB plasma." No patient makes red urine with this approach, and it's necessary when the ABO of the patient isn't known, but patients receiving ABO mismatched platelets use 50% more red cells, develop multi-organ failure more often, have more transfusion reactions and higher mortality rates than patients receiving ABO identical platelets(all observational data, but from multiple centers in surgical patients). O patients receiving AB plasma in large volumes have a 9% increase in mortality rate in Swedish data. We all know of rare case reports of fatal transfusion reactions from group O red cells given to non-O patients. Washed transfusions make these problems go away, in our experience. Is It Time to Reconsider the Concepts of "Universal Donor" and "ABO Compatible" Transfusions? Refaai MA, Cahill C, Masel D, Schmidt AE, Heal JM, Kirkley SA, Blumberg N. Anesth Analg. 2018 Jun;126(6):2135-2138. doi: 10.1213/ANE.0000000000002600. ABO-immune complex formation and impact on platelet function, red cell structural integrity and haemostasis: an in vitro model of ABO non-identical transfusion. Zaffuto BJ, Conley GW, Connolly GC, Henrichs KF, Francis CW, Heal JM, Blumberg N, Refaai MA. Vox Sang. 2016 Apr;110(3):219-26. doi: 10.1111/vox.12354. Epub 2015 Nov 3 Improved outcomes in acute myeloid leukemia patients treated with washed transfusions. Greener D, Henrichs KF, Liesveld JL, Heal JM, Aquina CT, Phillips GL 2nd, Kirkley SA, Milner LA, Refaai MA, Mendler JH, Szydlowski J, Masel D, Schmidt A, Boscoe FP, Schymura MJ, Blumberg N. Am J Hematol. 2017 Jan;92(1):E8-E9. doi: 10.1002/ajh.24585. A randomized trial of washed red blood cell and platelet transfusions in adult acute leukemia [ISRCTN76536440]. Blumberg N, Heal JM, Rowe JM. BMC Blood Disord. 2004 Dec 10;4(1):6. Washing red blood cells and platelets transfused in cardiac surgery reduces postoperative inflammation and number of transfusions: results of a prospective, randomized, controlled clinical trial. Cholette JM, Henrichs KF, Alfieris GM, Powers KS, Phipps R, Spinelli SL, Swartz M, Gensini F, Daugherty LE, Nazarian E, Rubenstein JS, Sweeney D, Eaton M, Lerner NB, Blumberg N. Pediatr Crit Care Med. 2012 May;13(3):290-9. doi: 10.1097/PCC.0b013e31822f173c.
  21. Most patients only need one red cell for surgery, or less. The need for the second is usually emergent and there is insufficient time for washing (takes at least 30 minutes). Just logistics and demographics. Ideally, all patients would receive washed red cells, but there is not yet convincing data that clinical outcomes are improved. There were trends to improved outcomes in our randomized trial (mortality in particular) but the trial was powered to demonstrate that washed red cells reduced post-transfusion reduced inflammation, as measured by IL-6 and CRP, which was conclusively demonstrated.
  22. There are no data. When we wash platelets or red cells, the outdate is 24 hours because of the open system (ancient COBE/Terumo type 2991s). Patients do better in terms of key clinical outcomes (mortality, infection, thrombosis) with washed platelets so I'm not concerned about the container, length of storage, etc. Ultimately clinical outcomes are more important than any of those surrogate in vitro markers. We routinely wash to remove incompatible ABO antibody and soluble antigen, FYI. We do not wash red cells more than 21 days of storage due to increased hemolysis, and poorer clinical outcomes with these components (washed >21 days). We currently wash with normal saline, but Plasma-Lyte A (AJCP in press) causes less hemolysis and we will be moving away from normal saline. Hopefully we remove normal saline from use for all transfusion service and clinical uses, due to recent data that normal saline causes increased mortality and renal failure in ICU patients (in NEJM). See references below. A randomized trial of washed red blood cell and platelet transfusions in adult acute leukemia [ISRCTN76536440]. Blumberg N, Heal JM, Rowe JM. BMC Blood Disord. 2004 Dec 10;4(1):6. Providing ABO-identical platelets and cryoprecipitate to (almost) all patients: approach, logistics, and associated decreases in transfusion reaction and red blood cell alloimmunization incidence. Henrichs KF, Howk N, Masel DS, Thayer M, Refaai MA, Kirkley SA, Heal JM, Blumberg N. Transfusion. 2012 Mar;52(3):635-40. doi: 10.1111/j.1537-2995.2011.03329.x. Epub 2011 Sep 2. Washing red blood cells and platelets transfused in cardiac surgery reduces postoperative inflammation and number of transfusions: results of a prospective, randomized, controlled clinical trial. Cholette JM, Henrichs KF, Alfieris GM, Powers KS, Phipps R, Spinelli SL, Swartz M, Gensini F, Daugherty LE, Nazarian E, Rubenstein JS, Sweeney D, Eaton M, Lerner NB, Blumberg N. Pediatr Crit Care Med. 2012 May;13(3):290-9. doi: 10.1097/PCC.0b013e31822f173c. ABO identical and washed blood transfusions as candidate strategies to reduce early mortality in acute promyelocytic leukemia. Sahai T, Henrichs K, Refaai M, Heal JM, Kirkley SA, Schmidt AE, Mendler JH, Masel D, Liesveld J, Aquina C, Blumberg N. Leuk Res. 2017 Nov;62:1-3. doi: 10.1016/j.leukres.2017.09.011. Epub 2017 Sep 23. Improved outcomes in acute myeloid leukemia patients treated with washed transfusions. Greener D, Henrichs KF, Liesveld JL, Heal JM, Aquina CT, Phillips GL 2nd, Kirkley SA, Milner LA, Refaai MA, Mendler JH, Szydlowski J, Masel D, Schmidt A, Boscoe FP, Schymura MJ, Blumberg N. Am J Hematol. 2017 Jan;92(1):E8-E9. doi: 10.1002/ajh.24585. Longer RBC storage duration is associated with increased postoperative infections in pediatric cardiac surgery. Cholette JM, Pietropaoli AP, Henrichs KF, Alfieris GM, Powers KS, Phipps R, Spinelli SL, Swartz M, Gensini F, Daugherty LE, Nazarian E, Rubenstein JS, Sweeney D, Eaton M, Blumberg N. Pediatr Crit Care Med. 2015 Mar;16(3):227-35. doi: 10.1097/PCC.0000000000000320. Transfus Apher Sci. 2018 Feb;57(1):127-131. doi: 10.1016/j.transci.2018.02.021. Epub 2018 Feb 21. 0.9% NaCl (Normal Saline) - Perhaps not so normal after all? Blumberg N1, Cholette JM2, Pietropaoli AP3, Phipps R4, Spinelli SL5, Eaton MP6, Noronha SA7, Seghatchian J8, Heal JM9, Refaai MA9. Crystalloid infusion is widely employed in patient care for volume replacement and resuscitation. In the United States the crystalloid of choice is often normal saline. Surgeons and anesthesiologists have long preferred buffered solutions such as Ringer's Lactate and Plasma-Lyte A. Normal saline is the solution most widely employed in medical and pediatric care, as well as in hematology and transfusion medicine. However, there is growing concern that normal saline is more toxic than balanced, buffered crystalloids such as Plasma-Lyte and Lactated Ringer's. Normal saline is the only solution recommended for red cell washing, administration and salvage in the USA, but Plasma-Lyte A is also FDA approved for these purposes. Lactated Ringer's has been traditionally avoided in these applications due to concerns over clotting, but existing research suggests this is not likely a problem. In animal models and clinical studies in various settings, normal saline can cause metabolic acidosis, vascular and renal function changes, as well as abdominal pain in comparison with balanced crystalloids. The one extant randomized trial suggests that in very small volumes (2 l or less) normal saline is not more toxic than other crystalloids. Recent evidence suggests that normal saline causes substantially more in vitro hemolysis than Plasma-Lyte A and similar solutions during short term storage (24 hours) after washing or intraoperative salvage. There are now abundant data to raise concerns as to whether normal saline is the safest replacement solution in infusion therapy, red cell washing and salvage, apheresis and similar uses. In the USA, Plasma-Lyte A is also FDA approved for use with blood components and is likely a safer solution for these purposes. Its only disadvantage is a higher cost. Additional studies of the safety of normal saline for virtually all current clinical uses are needed. It seems likely that normal saline will eventually be abandoned in favor of safer, more physiologic crystalloid solutions in the coming years. N Engl J Med. 2018 Mar 1;378(9):829-839. doi: 10.1056/NEJMoa1711584. Epub 2018 Feb 27. Balanced Crystalloids versus Saline in Critically Ill Adults. Semler MW1, Self WH1, Wanderer JP1, Ehrenfeld JM1, Wang L1, Byrne DW1, Stollings JL1, Kumar AB1, Hughes CG1, Hernandez A1, Guillamondegui OD1, May AK1, Weavind L1, Casey JD1, Siew ED1, Shaw AD1, Bernard GR1, Rice TW1; SMART Investigators and the Pragmatic Critical Care Research Group. 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 intensive care units at an academic center, we assigned 15,802 adults to receive saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer's solution or Plasma-Lyte A) according to the randomization of the unit to which they were admitted. The primary outcome was a major adverse kidney event within 30 days - a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) - all censored at hospital discharge or 30 days, whichever occurred first. RESULTS: Among the 7942 patients in the balanced-crystalloids group, 1139 (14.3%) had a major adverse kidney event, as compared with 1211 of 7860 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P=0.04). In-hospital mortality at 30 days was 10.3% in the balanced-crystalloids group and 11.1% in the saline group (P=0.06). The incidence of new renal-replacement therapy was 2.5% and 2.9%, respectively (P=0.08), and the incidence of persistent renal dysfunction was 6.4% and 6.6%, respectively (P=0.60). CONCLUSIONS: Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SMART-MED and SMART-SURG ClinicalTrials.gov numbers, NCT02444988 and NCT02547779 .).
  23. "A relapse would involve both the ABO and the Rh types, would it not?" One can have a relapse with recipient cells, and still have donor cells present, which in this case would be Rh positive, yes? If both donor and recipient types are present (as Malcolm suggests testing) you could have both O+ and A- cells, something we've seen on rare occasions. Sometimes one cannot rely on mixed field typing to explain what's going on clinically. Usually with relapse, the graft is lost, but not always completely. Relapse is usually obvious on peripheral smear and cytogenetics. If the patient had been typed as A+ elsewhere due to the presence of both donor and recipient red cells, the patient might be transfused with A+ cells if that facility did not have a correct history and did not observe mixed field typing. In this situation, we would probably transfuse washed O+ red cells.
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