[Automatically generated] From the JAMA Network, this is JAMA Clinical Reviews, Interviews and Ideas about Innovations in Medicine, Science and Clinical Practice. Here's your host. I'm Dr. Gregory Curfman, and I'm the Executive Editor of JAMA. I'm speaking today with Dr. Ryan Metcalf, who is Section Chief of Transfusion Medicine at University of Utah Health. Dr. Metcalf is the lead author of a recent special communication, now published at jamanetwork.org, which is titled, PLATELET Transfusion International Clinical Practice Guidelines. Welcome to the podcast, Dr. Metcalf. Oh, it's my pleasure. Thank you for having me. Now, Dr. Metcalf, your JAMA article includes many details about the clinical use of PLATELET Transfusion. But today, we want to focus on some of the main principles. And one central issue is the distinction between restrictive and liberal application of PLATELET Transfusion. And I wonder if you could please define that distinction for our listeners and talk a little about its clinical importance. Absolutely. That's a great question. And readers and listeners might be familiar with the terms restrictive and liberal transfusion strategies for red blood cell transfusion trials, the very hemoglobin thresholds and clinical practice guidelines for red blood cell transfusion. And we applied a similar concept or paradigm for PLATELET Transfusion. In general, you can define restrictive PLATELET Transfusion strategies within a randomized trial as the arm that got fewer amounts of platelets, whereas the liberal arm got greater amounts of platelet transfusions. And what we did was we evaluated randomized trials across different patient populations where patients were randomized to either get restrictive or liberal PLATELET Transfusion strategies. And then we looked at common effects across populations for the most important outcomes the panel decided upon, which were mortality and bleeding related outcomes. I wonder if you could give our listeners two or three examples of specific clinical situations in which a restrictive PLATELET Transfusion strategy as compared with a liberal strategy would be indicated just to sort of ground these general principles in some clinical examples. Absolutely. So I think one example that might sound a little familiar to those familiar with PLATELET Transfusion strategies, a lot of trials have been performed in hematology, oncology, patient populations, those with hypo proliferative thrombocytopenia, who may get considered for PLATELET Transfusion for prophylaxis to prevent bleeding. And we made a recommendation in non-bleeding patients with hypo proliferative thrombocytopenia, actively receiving chemotherapy or undergoing allogeneic stem cell transplant for a restrictive strategy that we defined as transfusing when the PLATELET count drops below 10,000 per microliter, because when we evaluated randomized trials in this patient population or broader patient population of hypo proliferative thrombocytopenia, we found no important benefit to liberal strategies or evidence of important harm with restrictive strategies. And so for that reason, we made a recommendation for restrictive. And when we chose a restrictive threshold that was particular, we tried to do it in a practical way that was practical for clinicians to implement, because we recognized that different trials, even within the same population, may have had slightly different restrictive versus liberal platelet transfusion strategies chosen. And so that was part of what we discussed as a guideline panel, and ultimately tried to come up with what we thought were rational and practical for implementation strategies for platelet transfusion. So that's one example. Another example that I'd like to mention, because we took a little bit of a different approach to analysis, would be we made a strong recommendation for restrictive platelet transfusion strategy in patients undergoing lumbar puncture who have thrombocytopenia. And in contrast to a lot of other areas where we evaluated evidence if randomized trials existed, we didn't have randomized trial evidence here, but we were still able to generate what we called moderate certainty evidence under Gray and Methodology because we hypothesized that the most important outcome of spinal hematoma, which is a very important catastrophic outcome, was near zero even among patients with very low platelet counts. And so we looked at observational studies rather than randomized trials, because they really didn't exist comparing different platelet strategies. Indeed, we found across multiple studies, reporting spinal hematoma rates, that the rates were exceedingly low. And for that reason, we made a more restrictive recommendation than, for example, the 2015 AABB guidelines where 50,000 as a platelet count threshold, less than 50,000 was used. Here we used less than 20,000, which will be a bit of a change compared to the prior AAB guidelines. But we also observed, again, exceedingly low event rates for that most important outcome. That's another example of rationale for what we applied. And then another important patient population. I'd like to talk about adult patients with spontaneous or traumatic non-operative intracranial hemorrhage with platelet counts greater than 100,000, including those receiving anti-platelet agents. The prior AAB guideline actually did not make a recommendation for this patient population. But as we evaluated evidence across multiple clinical settings and then considered really the lone clinical trial for this patient population, we didn't see clear evidence of benefit for liberal transfusion strategy again. And here, interestingly, even though this was not a patient population like hematology, oncology, where no prophylaxis or no platelet transfusion is commonly used, this is another setting where the patient maybe already is bleeding, but the restrictive arm involved no platelet transfusion. And if anything, the trial suggested the possibility for harm with platelet transfusion. There's some additional nuances that I probably won't go into today, but at any rate, we made a conditional recommendation in that setting for no platelet transfusion, meeting those specific patient population clinical criteria based on low to very low certainty evidence. Okay, that's excellent. And I wonder for our general listeners, I wonder if you could say a little more about to what extent the platelet count affects the decision to transfuse. This may be different in different clinical situations, but are there any overarching principles regarding the use of the platelet count as a guide? One way to think about it, at least when we think about biological plausibility, patients with thrombocytopenia, if they have important rates of bleeding, the possibility of transfusing platelets could reduce the risk of bleeding or could help to treat bleeding. So as far as what exact platelet count becomes pertinent, well, if we look at the randomized trials that exist, they vary the restrictive and liberal definitions platelet counts used for trials that evaluated those, depending on the clinical population. And one way perhaps to think about it is sort of like stress to the hemostatic system. So in settings where bleeding is not occurring yet and there are perhaps lower stresses to the hemostatic system, restrictive and liberal definitions might have included lower platelet counts in general. So hematology, oncology patients getting prophylactic platelet transfusions, for example. Whereas other examples, major non-neuraxial surgery, the platelet count threshold that we recommended was less than 50,000. So that's a higher platelet count. And part of the rationale there, even though we didn't really have great direct evidence for that particular group, was stress to the hemostatic system would be expected to be greater in a patient population like that. The extreme restrictive strategy would be to administer platelet transfusions in therapeutic situations, but not prophylactic situations. And I wonder if you could comment about the advisability of that more extreme approach. When we think about the benefits of restrictive strategies, one of them based on our patient values and preferences is avoiding adverse events. Another one is to help maintain an adequate platelet supply for those most likely to benefit. And our thinking there is that the bleeding patient could be the patient that is most likely to benefit on average, potentially compared to a patient that is not bleeding. So I think there's a potential rationale there. But at the same time, we see in trials, even among patients that perhaps aren't bleeding yet, bleeding rates still remain, but some might consider high, important bleeding rates. And that's regardless of whether restrictive or liberal platelet transfusion strategies are used. So we recognize also that there may still be important rates of bleeding. And that's why thinking about other things in future research directions related to alternatives to platelet transfusion, of course, additional randomized trials are always welcome as well. That is one way to think about things, but at the same time, it's important to recognize that rates of bleeding still may remain relatively high, even in the prophylactic setting. Your guideline covers both the adult population and the pediatric population. Are there any general differences in the way you would think about the use of blood transfusions in adults versus children? We talked to our pediatric colleagues about this, and some have cited there's some data to suggest that potentially bleeding rates are perhaps a little bit higher in pediatric populations in hematology, oncology, for example, compared to adult populations. But nevertheless, we looked at where we had evidence available, the relative effects of restrictive versus liberal, and again, did not find great evidence to suggest that there was a benefit to liberal, rather we favored the unequivocal benefits of restrictive, avoiding adverse events, and maintaining the blood supply. So we did want to have as much impact as possible, pediatric patients as much as it was possible and applicable. So where we had evidence certainly from randomized trials, we would include pediatric patient populations as much as possible, and recommendations related to those and other populations where we didn't have any evidence in pediatric patient populations. We tried to be careful to make the recommendations just for adult patients and be explicit about that. So mentioning which ones applied more broadly to adults and pediatric patients, more to neonates for neonatal recommendation versus adults, where we explicitly said adults, that meant it was limited to adults. I wonder if you might have any final thoughts or lessons learned for our listeners. What do you consider the principal messages of your new clinical practice guideline for our listeners? So the principal message for us is that really the recommendation is overarchingly to implement restrictive platelet-less transfusion strategies across at least the populations that were included in the guideline. And we made 11 overall recommendations, four strong and seven conditional. And the reason we made what we called restrictive recommendations was that we didn't see clear evidence of benefit with liberal strategies for the most important outcomes of mortality and bleeding. And for that reason, we turned our attention to less important outcomes that were still important, but not as important as our main outcomes, but that were in a quivically beneficial for restrictive strategies. So, avoiding acute adverse events, maintaining adequate platelet supply for those most likely to benefit, and lastly, probably least importantly, based on our rankings, health care related costs. So, I think that's the overarching message. And with the publication of guidelines, implementation is another important project. That's something that we're going to turn our attention to. But, that's the gist of what we recommended. And then, I also want to just mention to listeners that we included a good practice statement that essentially says, look at the patient overall clinical context. We chose what we thought were practical thresholds for implementation. For example, if it's a platelet count threshold, we felt it was practical. But of course, there can be important variation in clinical context. And so, we tried to describe that a bit in our good practice statement to help clinicians make optimal decisions in line with patients' values and preferences. Well, thank you very much, Dr. Metcalf, for this very interesting discussion on a very important clinical topic. Thanks so much for having me. Appreciate it. I'm Dr. Gregory Curfman, and I've been speaking with Dr. Ryan Metcalf about a new clinical practice guideline on platelet transfusion. You can find a link to his JAMA article in this episode's description. This episode was produced by Shelly Steffens at the JAMA Network. To follow this and other JAMA Network podcasts, please visit us online at jamanetworkaudio.com or search for JAMA Network wherever you get your podcasts. Thanks for listening. This content is protected by copyright by the American Medical Association with all rights reserved, including those for text and data mining, AI training and similar technologies.