Hello, I'm Dr. Kenneth Remy from University Hospitals in Cleveland and Rainbow Babies and Children's Case Western University School of Medicine. I have the pleasure today to report on a recent group of publications that our group has been fortunate to publish upon with the Taxi Cab Control and Avoidance of Bleeding Initiative led by Dr. Mary Ann Nellis. I'm going to add to the conversations this morning from the other two presentations by presenting on the research priorities and implementation. And just as a review, Transfusion Anemia Expertise Initiative or TAXI, Control Avoidance of Bleeding and CAB convened an expert panel to rigorously evaluate the medical literature with goals to develop evidence-based and when evidence is lacking, expert-based consensus statements to guide transfusion and blood management practices to create an implementation initiative and then to develop research priorities. I will be discussing the last two. Our team has been led by a unique group of individuals, including Robert Parker, Stacey Valentine, Scott Bateman, Oliver Karam, and our leader in chief, Mary Ann Nellis at Cornell, who were funded by the NHLBI R13 mechanism to be able to get this initiative executed. In the assembly of the expert panel, we had a number of individual pediatric intensivists, pediatric anesthesiologists, pediatric surgeons, CT surgeons, neurosurgeons, emergency medicine physicians, and individuals as part of pediatric transfusion medicine. And this expert panel met over a period of two years and at the conclusion of this made guidelines that were recently published in the Pediatric Critical Care Medicine Journal of the Society of Critical Care Medicine. This endeavor was also led by the Pediatric Acute Lung Injury and Sepsis Investigators and has partnered with a number of different societies. To this vein, we were fortunate to be able to develop research priorities after an exhausting evaluation of the literature. It provided opportunities to unearth areas that were ripe for potential early research so that we could best improve the current quality of the level of evidence. And this was published in January of 2022. From our defined subgroups, which had an original primary objective, we were able to identify these research priorities in each area. These areas included laboratory measures used to guide transfusion, product characteristics, TBI intracranial hemorrhage, trauma, cardiac surgery, ECMO, oncology and stem cell transplantation patients, liver failure and transplantation, sepsis and DIC, invasive procedures outside of the operating suite, and non-cardiac surgery. This group then developed these overarching research priorities that were applicable first to across all critically ill children, as well as some specific to each subgroup. The general and specific areas of these research priorities centered in and around four areas. We defined bleeding and blood loss. We had endeavored to understand mechanisms driving both efficacy and harm in plasma and platelet transfusions. We wanted to identify thresholds or triggers to weigh the risk-benefit ratio. And we wanted to identify optimal dosing timing and the order in which transfusions could be administered. And four overarching themes across all subgroups of critically ill patients were identified. Number one, we recommend studies to validate the definitions of bleeding and blood loss with specific impact of the location of bleeding in critically ill children. Two, we recommend studies to examine the mechanisms driving both efficacy and harm in platelet and plasma transfusion. Three, we recommend studies that describe thresholds or triggers to weigh the risk-benefit ratio in tolerating a coagulation abnormality or thrombocytopenia versus a risk-benefit ratio of giving a plasma or platelet transfusion in a critically ill child. And finally, we recommend studies that seek to determine that optimal dose timing and order in which plasma and platelet transfusions are administered with respect to each other and to hemostatic interventions in order to decrease the risk of bleeding or stop active bleeding in critically ill children. One unique thing that came from this TAXICAB initiative is that many observational studies, both retrospective and small prospective studies, have certainly tempered our enthusiasm to understand where areas are ripe for future research. Clearly, the field needs to grow in these areas. We need to define functional research areas that endeavor research laboratory studies that are functional-based and not just quantitative-based, and then conduct robust prospective randomized control trials that utilizes these indices. Let's take a look at each of the subgroups. In severe trauma TBI and non-traumatic ICH, we identified that in children with these issues, we recommended future studies to determine if goal-directed resuscitation compared with an empiric ratio approach may provide benefit in predetermined patient-centered outcomes. Secondarily, in TBI, especially children with severe TBI, we recommend future studies to determine if and at what laboratory cutoff platelet or plasma should be administered to ensure safe placement of an ICP monitor. For cardiopulmonary bypass, in children and infants undergoing cardiac surgery with bypass, we need to further refine and determine the benefits and risks associated with the administration of platelet and plasma transfusions, either in the prime, on bypass, after separation of bypass, and certainly taking into account the patient's age and weight. For ECMO, similar to cardiopulmonary bypass, we recommend that all blood product exposure, including plasma and platelets, within the circuit prime be reported in the pediatric ECMO transfusion studies and in quality improvement projects. In our stem cell and oncology patients, we recommend investigations surrounding continuous versus bolus infusions of platelets, various platelet products, and indications for and efficacy of transfusion, not just count, in pediatric oncology transplant patients. Two, we recommend studies to determine the optimal platelet and plasma transfusion strategies for, number one, prophylaxis, and two, control of clinically relevant bleeding in these patient populations, especially those with specific nervous system pathologies, including brain tumors, ischemic hemorrhagic stroke, subdural hematomas, spinal cord tumors, metastases, and others. For our liver failure and transplantation patients, we recommend investigations that evaluate diagnosis and treatment of these underlying coagulopathic bleeding and transfusion indications, including specific targets and thresholds in bleeding and non-bleeding critically with acute liver failure and following liver transplantation. We do recommend that in these research priorities that we should develop an individualized patient approach to diagnose and management coagulopathic bleeding with an emphasis on toleration of coagulopathy and in promoting restrictive transfusion strategies when indicated. For non-cardiac surgery, we recommend research that seeks to evaluate the optimal plasma and platelet transfusion thresholds and targets and transfusion strategies for critically ill children undergoing non-cardiac procedures. This additionally should also include an individualized patient approach to diagnose and manage these coagulopathic bleeding with emphasis on a restrictive transfusion strategy. Similar research priorities we developed were related to invasive procedures. We recommend that in children undergoing lumbar puncture to understand the relationship between abnormal hemostasis and coagulopathy and the risk of bleeding and or adverse events with the effect of plasma transfusions or platelets. Furthermore, we recommend with central venous line placement insertion to determine whether prophylactic platelet or plasma transfusions are needed and to determine the minimal platelet count, the maximal INR-PT ratio, and to maximize their activated partial thromboplastin time for safe placement of the catheter. In DIC and sepsis, we recommend studies to evaluate specific indications and or transfusion strategies to direct platelet and plasma transfusion on all patients with degrees of bleeding. So if you look at the subgroup so far, there seems to be a common theme. One thing that's certainly true is that we've governed and guided our transfusions, generally in pediatrics and in adults, by using a quantitative measure. Specifically, we look at use of PT-INR, PTT, and platelet count, but these necessarily do not measure a function of platelets and or of the plasma that's delivered, let alone what's going on in vivo with hemostasis and coagulation. And so clearly, there's an undefined area that needs to be defined as we move forward in this field. And so in the laboratory assays to predict need for plasma transfusion, as one can imagine, we need and recommend future investigations to determine the efficacy of functional tests of hemostasis and coagulation. Both standard coagulation assessment and viscoelastometric testing into prediction of critically ill children with development of test-based triggers for both platelet and plasma transfusion. We believe that this research priority will help guide the others so that we can develop robust, objective, functional measures that can guide individual platelet and plasma transfusion. And finally, in the product selection and in processing, we recommend studies to investigate how physiologic measures and outcomes are affected by the transfusion of different types of plasma and platelet. We recommend understanding and examining the effect of these different types of plasma and platelet products on endothelial function, as well as adverse reactions associated with these. And furthermore, we recommend the same with platelets. So we're fortunate in our group that we were able to develop a robust research priority list so that the next couple years of transfusion research could be guided by these areas that certainly are ripe and have unclear areas that need to further be evaluated and developed. Now in this process, one might imagine that we need to develop a robust implementation strategy so that we can help guide based off of our recommendations from this Taxi-Cab Initiative changes perhaps in the way that we manage children with platelet and plasma transfusion. Now one of the challenges. So what you're looking at here is in publication from Marian Nellis in Pediatric Critical Care Medicine from our primary executive summary are the two decision trees that go on for clinicians specifically when deciding whether or not to transfuse plasma or platelets. I show this because implementation certainly an alteration in how we transfuse presently is certainly going to be tempered and understanding how clinicians at the bedside make these careful decisions and it's not as simple as just, nope, you need to just only transfuse under these circumstances because we know that in vivo patients are more complicated than just a simple guideline and certainly understanding what goes into decision making for transfusion would be important as we attempt to implement new strategies for better evidence-based practices. And so as you look at these different decision trees, each of these decision points allows an opportunity where implementation could occur and this occurs not only in the clinician at the bedside, it also occurs with those developing the products, those individuals that are sending those products to the bedside and then certainly understanding the implications of the response of these products. In one article that came out of Delaforce and Implementation Science in 2020, the authors evaluated barriers and implementation strategies to understand specifically across a number of different studies in a systematic review, how to better improve barriers and delivery of new blood transfusion strategies. And as you can see here, a common theme certainly arise in multiple of these publications. If you look, conducting local consensus discussions, developing education materials, reminding allowing incentive and allowance structures, providing feedback based off of transfusion practices across the board, many of these are certainly common. Education is going to be a much of a need here in our implementation strategy of these taxicab initiatives. Understanding local practices is going to be vital to be able to develop robust education at the local level, and more importantly, develop systems that are specific to each institution, whether that's development of new electronic medical record implementation strategies, whether that's using paper at the bedside with clinicians and nurses partnering to develop better ways to understand which child requires a transfusion, or if it's going to provide different opportunities for feedback for clinicians that are driven by objective evidence-based practices, not just historic dogma that, oh, the platelet count is 10,000. We need to transfuse this patient. That may not be robust enough in going into the future as we develop these additional research priorities and further refine the level of evidence that supports the way that we transfuse our children with plasma and platelets. And so one such implementation strategy as recommended by taxicab could be the development of a best practice advisory that exists in your individual electronic medical record that provides you the opportunity when making a decision to transfuse a child. Why am I getting this? So in red blood cell, for instance, as the previous taxi group came up with in implementation, is this stop measure that at the time of transfusion, it queries the individual that's ordering the transfusion to make sure that the patient truly requires this. As we know, blood products are not benign. They certainly have very significant adverse consequences, and understanding which patients would best benefit based off of a rigorous evidence-based approach with defined research studies is important, and it's certainly paramount, so that we can limit this scarce resource to only be reused under the circumstances that it would be beneficial while minimizing harm. And one such implementation strategy is to certainly integrate this within local electronic medical records. So in conclusion, although plasma and platelet transfusions are administered frequently to critically ill children, evidence to guide this practice is lacking. There is a clear need for large-scale studies of plasma and platelet transfusion studies in critically ill children. Future studies should be focused on efficacy and harm, thresholds to balance the risk-benefit ratio, optimizing dosing and timing, as well as validated outcomes in critically ill children receiving these plasma and or platelet transfusion. And finally, a robust implementation strategy is needed at individual centers across these centers and by societal recommendations that can subsequently change our current practices to reflect the best evidence-based practices so that we can ultimately move this field forward and help save children's lives. I'd like to first give thank you to our leader, Marianne Nellis. You know, it's said that it takes a village to be able to accomplish a lot of different endeavors such as this, but certainly at that village level, you need to have that leader, and Marianne has been exceptional in her development of this program and in leading the individual subgroups and across an interaction all with different societies so that we can disseminate this information. And for that, Marianne, congratulations, you did an outstanding job, and I'm most proud to have worked with you. And this is the list of other individuals who have certainly robustly put time into this effort, and thank you very much for that. Thank you for your time. I look forward to any questions.

Taxi Cab Control and Avoidance of Bleeding Initiative

evidence-based guidelines

transfusion and blood management practices

Pediatric Critical Care Medicine Journal

research priorities