EMS Timely Tips: Tranexamic Acid (TXA) use in Pediatric Trauma
Massive transfusion protocols have become vital tools used within trauma centers across the country. Appropriately so, as many emergency providers know that hemorrhage is the most common cause of death within the first hour of arrival to a trauma center. Most recently, a medication called Tranexamic Acid or TXA has been found to assist in life-saving measures for trauma victims in both the pre-hospital setting and the emergency department. But is TXA a recommended medication for kids? This podcast segment highlights the safe use of TXA in pediatric traumas and beyond.
Featured Speaker:
She is also active on the hospital trauma committee and authored the institutional protocol for tranexamic acid administration in pediatric trauma. She has provided outreach education to local EMS agencies regarding indications for TXA administration in pediatric trauma.
Jennifer Flint, MD
Jennifer Flint, MD, is board certified in internal medicine, pediatrics and pediatric critical care and spends most of her clinical time as a cardiac intensivist. Dr. Flint currently fulfills multiple roles as the hospital’s pediatric burn critical care director, PICU trauma committee liaison, pediatric stroke committee member, medical director of pediatric critical care transport, and clinical associate professor of pediatrics for the University of Missouri-Kansas City School of Medicine.She is also active on the hospital trauma committee and authored the institutional protocol for tranexamic acid administration in pediatric trauma. She has provided outreach education to local EMS agencies regarding indications for TXA administration in pediatric trauma.
Transcription:
EMS Timely Tips: Tranexamic Acid (TXA) use in Pediatric Trauma
Dr. Andrew Wilner: Welcome to another episode of Pediatrics in Practice with Children's Mercy, Kansas city. I'm your host, Dr. Andrew Wilner, Associate Professor of Neurology at the University of Tennessee Health Science Center, Memphis, Tennessee. My guest today is Dr. Jennifer Flint, Clinical Associate Professor of Pediatrics, University of Missouri, Kansas City School of Medicine and Medical Director, Pediatric Critical Care Transport at Children's Mercy, Kansas City. Today,
Dr. Flint will discuss the use of tranexamic acid in pediatric trauma. Welcome, Dr. Flint.
Dr. Jennifer Flint: Thank you.
Dr. Andrew Wilner: Thanks for joining us. Dr. Flint, let's get started. What's tranexamic acid anyway?
Dr. Jennifer Flint: Yeah. So tranexamic acid is a medication that's commonly used for a lot of things, specifically to help with the breakdown of a clot. So it inhibits plasminogen activation and plasmin activity and it helps prevent the fibrin clot that has formed from breaking down during a blood clot formation.
Dr. Andrew Wilner: So does it prevent bleeding or enhance bleeding?
Dr. Jennifer Flint: It enhances bleeding so it prevents that clot breakdown.
Dr. Andrew Wilner: Okay. So tell us, when would you want more bleeding rather than less?
Dr. Jennifer Flint: Well, so we're talking about trauma here, and in trauma, we know that hemorrhage is the most common cause of death within the first hour of trauma, and that's why we call that the golden hour. And coagulopathy, we know causes 80% of trauma deaths in the operating room as well as 50% of trauma deaths within the first 24 hours. So that's when it's important, when you've got a traumatic patient who is bleeding to try to do things to stop the bleeding. And that's where TXA comes into play.
Dr. Andrew Wilner: So does TXA then help stop bleeding?
Dr. Jennifer Flint: Yeah, so it is one of the things that can help prevent the clot from breaking down or if I bring a fibrinolysis and help the body form a better clot, a more formed clot during that clotting process.
Dr. Andrew Wilner: Ah, so it helps the body make a better clot and to keep the clot from breaking down.
Dr. Jennifer Flint: Correct.
Dr. Andrew Wilner: Okay. So it's supporting the clotting system rather than the other way around. Okay. That makes sense. That's great. So trauma, you mentioned the golden hour, so this would be, I don't know, some sort of accident, usually like a car accident or a gunshot, something like that?
Dr. Jennifer Flint: Sure.
Dr. Andrew Wilner: Right. Okay. So is there anything special about children and the way that their blood clots that's different than adults?
Dr. Jennifer Flint: Well, we do know that there are some differences within the clotting cascade in children. In a traumatic injury, we know both in kids and adults, we have what's called traumatic-induced coagulopathy and there's two forms of that. There's acute traumatic coagulopathy and that's intrinsic to the patient. That's where you have an injury that causes activation of your clotting cascade. And you serve to deplete all your internal clotting factors, and then you get hyperfibrinolysis, which causes a decrease in clot formation and clot stability. And that's where TXA can come into play to help stabilize that clot. You also have iatrogenic coagulopathy, which is all the things that we do to patients after they've been injured, such as giving them too much saline, hypothermia, not getting them warm. And both of these entities contribute to trauma-induced coagulopathy and more bleeding after traumatic injury, even for children.
Dr. Andrew Wilner: Is TXA something you would always use? In other words, patient in a protocol, patient rolls in the emergency room, they're bleeding and just hang the TXA regardless or is it something you wait and see whether the patient can kind of manage the bleeding with their own intrinsic clotting factors?
Dr. Jennifer Flint: Yeah. So, what we found in CRASH-2, CRASH-2 is a study that was published back in 2013 where they gave patients who had traumatic injury TXA. And what we found was that it's actually most effective if given within the first hour of injury and up to three hours after injury. If you give it three hours after their injury, there's actually some harm that can be associated with giving TXA. So for this medication, the sooner, the better.
Dr. Andrew Wilner: Well, clotting is kind of tricky because, well, I work with stroke and, of course, we're always trying to get rid of the clot that caused the stroke. So we give medication to dissolve the clot and it sounds like TXA is kind of the opposite. You want the blood to clot to stop the bleeding. Is that right?
Dr. Jennifer Flint: That is correct. So in hemorrhagic shock associated with trauma, a lot of centers will activate what's called a massive transfusion protocol. So we'll give things like, FFP and platelets and cryo and blood and TXA really augments that, because really, at the end of both of those clotting cascades, when you're activating your clotting system, holds that hyperfibrinolysis. So it shuts that down and it helps that clot from breaking down and makes it more stable.
Dr. Andrew Wilner: Since early is better, is this something that the EMS providers could give in the ambulance, when they, you know, arrive at the scene of an accident? Just here they come and put in the IV and start the TXA right away, or does the patient need a more thorough evaluation?
Dr. Jennifer Flint: This is absolutely a medication that we can give them by first responders and there are many local EMS agencies who carry TXA with them. So this is a medication that absolutely can be given in an IV form. It doesn't need to be diluted. And if you have a patient who has sustained a traumatic injury, even a pediatric patient, if they meet certain criteria, and they're a candidate for the TXA, it's something that is even best and most effective if given early in the field.
Dr. Andrew Wilner: Now, every medication that I've ever used has a downside. So what's the downside here of TXA?
Dr. Jennifer Flint: Well, in the studies that we have, in higher doses in children when they were studying TXA not related to trauma, but for other things, there was perhaps an increase incidence of seizures with higher doses. Now, the doses that are recommended for children for traumatic injuries have not been associated with seizures. You know, of course, we also worry that if we're stabilizing a clot, that perhaps you might cause more clots such as DVTs or strokes or other forms of blood clots, but we have not seen that in the literature when we've compared TXA to standard care.
Dr. Andrew Wilner: How new is TXA?
Dr. Jennifer Flint: It's been around for a long time. So we actually started using it in the 1980s for dental procedures for hemophiliacs. And we've used it quite a bit in the operating room for cardiac surgery in children, for spinal surgeries in children, for heavy menstrual bleeding. We've used it for a long time now and have started using it in traumatic injuries in 2013 when CRASH-2 came out.
Dr. Andrew Wilner: Are there any ongoing studies now to learn more about patient selection and dosing and things like that?
Dr. Jennifer Flint: Yeah. So, you know, of course, the adult literature always comes before the pediatric literature and we have very nice data in CRASH-2 and CRASH-3, as well as the MATTERs I and MATTERs II studies for adult patients. But we don't have a lot of good prospective data for children. We have the PTAC study, which is a retrospective study that also showed an improvement in mortality with the use of TXA. The pediatric TIC-TOC study is one that is coming down the pipeline. So, this is a pilot study that's trying to evaluate the feasibility of being able to enroll children in a randomized controlled trial using TXA for trauma. The study is closed and we are waiting for the paper. So I'm hopeful that will give us some more information and I'm hopeful that we'll be able to get a larger randomized controlled study for children.
Dr. Andrew Wilner: I'm just curious, how do you go about getting a consent when time is at such a premium, you want to give it right away. And usually, these events are unplanned, I would imagine. And the parents may or may not be readily available and you're dealing with minors. It seems like a lot of obstacles. How do you do a study like that?
Dr. Jennifer Flint: Yeah, and that is definitely one of the obstacles. So the TIC-TOC study is going to look at that process and the feasibility of getting consent or even potentially waiving consent. It'll depend on the study design and what the IRB will allow. But that's part of what the TIC-TOC study will be getting at, is this easibility of being able to enroll children in a timely manner.
Dr. Andrew Wilner: And of course, well, it's important to protect all of the subjects, but it's also important to get the research done so that people can get the optimal care.
Dr. Jennifer Flint: Yes. absolutely.
Dr. Andrew Wilner: Does the TXA kind of wash out of the system? So if a week later, you need to give the patient heparin or there's some other issue, like you mentioned DVT, it's all ancient history by the time those problems come around?
Dr. Jennifer Flint: Yeah. So the protocols for TXA and trauma call for a bolus dose that you run over 10 minutes. And then you run another eight-hour infusion. And so it's really just during the duration of that critical time period, right after a traumatic injury where they're at highest risk for bleeding. And so by that eight hours, your infusion is done. And then, you know, it clears from your systems. And if you needed to anticoagulate someone later on down the road for that, it would not interfere with that.
Dr. Andrew Wilner: You know, if you could sort of have a seminar for first responders about TXA, what would be your take-home message?
Dr. Jennifer Flint: So my take-home message is think about it and think about it early. If you have a patient, even a pediatric patient who has suffered a traumatic injury and they meet criteria, which a systolic blood pressure of less than 80 if you're five years or less, if your systolic blood pressure is less than 90 and you're older than five, or if you're hypotensive or not responding to a fluid bolus, or if you have obvious bleeding, if you come upon a scene and you have obvious bleeding, they're a candidate for TXA. If they're greater than 12 or they look an adult, give the adult dosing 1 gram IV over 10 minutes followed by a gram over eight hours, and we'll continue that when you get into the hospital. If they're less than 12, use how you estimate a child's weight in the field per your protocol, 15 per kilo over 10 minutes is the bolus dose. If you get that started, that is awesome. And then we would continue the infusion once they get to us at the hospital.
Dr. Andrew Wilner: Oh, that's fantastic. This has really been very informative, Dr. Flint. Is there anything else you'd like to tell our listeners before we conclude?
Dr. Jennifer Flint: I think it's really important, if your team is interested in coming up with a TXA protocol, to get with your local trauma center, your pediatric trauma center, and just make sure that you're on the same page, that everybody agrees on the dose and the criteria for administering it. And just make sure that your trauma center is supportive and that everyone agrees on the protocol that your team is considering implementing.
Dr. Andrew Wilner: Well, thanks very much, Dr. Flint. This has been a very informative discussion. Thanks for joining me on Pediatrics in Practice.
Dr. Jennifer Flint: Thank you very much. This was a great discussion today.
Dr. Andrew Wilner: This has been Pediatrics In Practice with Children's Mercy, Kansas City. Please remember to subscribe, rate and review this podcast and all the other Children's Mercy podcasts. To learn more, visit childrensmercy.org/ems. I'm your host, Dr. Andrew Wilner. Thanks for listening,
EMS Timely Tips: Tranexamic Acid (TXA) use in Pediatric Trauma
Dr. Andrew Wilner: Welcome to another episode of Pediatrics in Practice with Children's Mercy, Kansas city. I'm your host, Dr. Andrew Wilner, Associate Professor of Neurology at the University of Tennessee Health Science Center, Memphis, Tennessee. My guest today is Dr. Jennifer Flint, Clinical Associate Professor of Pediatrics, University of Missouri, Kansas City School of Medicine and Medical Director, Pediatric Critical Care Transport at Children's Mercy, Kansas City. Today,
Dr. Flint will discuss the use of tranexamic acid in pediatric trauma. Welcome, Dr. Flint.
Dr. Jennifer Flint: Thank you.
Dr. Andrew Wilner: Thanks for joining us. Dr. Flint, let's get started. What's tranexamic acid anyway?
Dr. Jennifer Flint: Yeah. So tranexamic acid is a medication that's commonly used for a lot of things, specifically to help with the breakdown of a clot. So it inhibits plasminogen activation and plasmin activity and it helps prevent the fibrin clot that has formed from breaking down during a blood clot formation.
Dr. Andrew Wilner: So does it prevent bleeding or enhance bleeding?
Dr. Jennifer Flint: It enhances bleeding so it prevents that clot breakdown.
Dr. Andrew Wilner: Okay. So tell us, when would you want more bleeding rather than less?
Dr. Jennifer Flint: Well, so we're talking about trauma here, and in trauma, we know that hemorrhage is the most common cause of death within the first hour of trauma, and that's why we call that the golden hour. And coagulopathy, we know causes 80% of trauma deaths in the operating room as well as 50% of trauma deaths within the first 24 hours. So that's when it's important, when you've got a traumatic patient who is bleeding to try to do things to stop the bleeding. And that's where TXA comes into play.
Dr. Andrew Wilner: So does TXA then help stop bleeding?
Dr. Jennifer Flint: Yeah, so it is one of the things that can help prevent the clot from breaking down or if I bring a fibrinolysis and help the body form a better clot, a more formed clot during that clotting process.
Dr. Andrew Wilner: Ah, so it helps the body make a better clot and to keep the clot from breaking down.
Dr. Jennifer Flint: Correct.
Dr. Andrew Wilner: Okay. So it's supporting the clotting system rather than the other way around. Okay. That makes sense. That's great. So trauma, you mentioned the golden hour, so this would be, I don't know, some sort of accident, usually like a car accident or a gunshot, something like that?
Dr. Jennifer Flint: Sure.
Dr. Andrew Wilner: Right. Okay. So is there anything special about children and the way that their blood clots that's different than adults?
Dr. Jennifer Flint: Well, we do know that there are some differences within the clotting cascade in children. In a traumatic injury, we know both in kids and adults, we have what's called traumatic-induced coagulopathy and there's two forms of that. There's acute traumatic coagulopathy and that's intrinsic to the patient. That's where you have an injury that causes activation of your clotting cascade. And you serve to deplete all your internal clotting factors, and then you get hyperfibrinolysis, which causes a decrease in clot formation and clot stability. And that's where TXA can come into play to help stabilize that clot. You also have iatrogenic coagulopathy, which is all the things that we do to patients after they've been injured, such as giving them too much saline, hypothermia, not getting them warm. And both of these entities contribute to trauma-induced coagulopathy and more bleeding after traumatic injury, even for children.
Dr. Andrew Wilner: Is TXA something you would always use? In other words, patient in a protocol, patient rolls in the emergency room, they're bleeding and just hang the TXA regardless or is it something you wait and see whether the patient can kind of manage the bleeding with their own intrinsic clotting factors?
Dr. Jennifer Flint: Yeah. So, what we found in CRASH-2, CRASH-2 is a study that was published back in 2013 where they gave patients who had traumatic injury TXA. And what we found was that it's actually most effective if given within the first hour of injury and up to three hours after injury. If you give it three hours after their injury, there's actually some harm that can be associated with giving TXA. So for this medication, the sooner, the better.
Dr. Andrew Wilner: Well, clotting is kind of tricky because, well, I work with stroke and, of course, we're always trying to get rid of the clot that caused the stroke. So we give medication to dissolve the clot and it sounds like TXA is kind of the opposite. You want the blood to clot to stop the bleeding. Is that right?
Dr. Jennifer Flint: That is correct. So in hemorrhagic shock associated with trauma, a lot of centers will activate what's called a massive transfusion protocol. So we'll give things like, FFP and platelets and cryo and blood and TXA really augments that, because really, at the end of both of those clotting cascades, when you're activating your clotting system, holds that hyperfibrinolysis. So it shuts that down and it helps that clot from breaking down and makes it more stable.
Dr. Andrew Wilner: Since early is better, is this something that the EMS providers could give in the ambulance, when they, you know, arrive at the scene of an accident? Just here they come and put in the IV and start the TXA right away, or does the patient need a more thorough evaluation?
Dr. Jennifer Flint: This is absolutely a medication that we can give them by first responders and there are many local EMS agencies who carry TXA with them. So this is a medication that absolutely can be given in an IV form. It doesn't need to be diluted. And if you have a patient who has sustained a traumatic injury, even a pediatric patient, if they meet certain criteria, and they're a candidate for the TXA, it's something that is even best and most effective if given early in the field.
Dr. Andrew Wilner: Now, every medication that I've ever used has a downside. So what's the downside here of TXA?
Dr. Jennifer Flint: Well, in the studies that we have, in higher doses in children when they were studying TXA not related to trauma, but for other things, there was perhaps an increase incidence of seizures with higher doses. Now, the doses that are recommended for children for traumatic injuries have not been associated with seizures. You know, of course, we also worry that if we're stabilizing a clot, that perhaps you might cause more clots such as DVTs or strokes or other forms of blood clots, but we have not seen that in the literature when we've compared TXA to standard care.
Dr. Andrew Wilner: How new is TXA?
Dr. Jennifer Flint: It's been around for a long time. So we actually started using it in the 1980s for dental procedures for hemophiliacs. And we've used it quite a bit in the operating room for cardiac surgery in children, for spinal surgeries in children, for heavy menstrual bleeding. We've used it for a long time now and have started using it in traumatic injuries in 2013 when CRASH-2 came out.
Dr. Andrew Wilner: Are there any ongoing studies now to learn more about patient selection and dosing and things like that?
Dr. Jennifer Flint: Yeah. So, you know, of course, the adult literature always comes before the pediatric literature and we have very nice data in CRASH-2 and CRASH-3, as well as the MATTERs I and MATTERs II studies for adult patients. But we don't have a lot of good prospective data for children. We have the PTAC study, which is a retrospective study that also showed an improvement in mortality with the use of TXA. The pediatric TIC-TOC study is one that is coming down the pipeline. So, this is a pilot study that's trying to evaluate the feasibility of being able to enroll children in a randomized controlled trial using TXA for trauma. The study is closed and we are waiting for the paper. So I'm hopeful that will give us some more information and I'm hopeful that we'll be able to get a larger randomized controlled study for children.
Dr. Andrew Wilner: I'm just curious, how do you go about getting a consent when time is at such a premium, you want to give it right away. And usually, these events are unplanned, I would imagine. And the parents may or may not be readily available and you're dealing with minors. It seems like a lot of obstacles. How do you do a study like that?
Dr. Jennifer Flint: Yeah, and that is definitely one of the obstacles. So the TIC-TOC study is going to look at that process and the feasibility of getting consent or even potentially waiving consent. It'll depend on the study design and what the IRB will allow. But that's part of what the TIC-TOC study will be getting at, is this easibility of being able to enroll children in a timely manner.
Dr. Andrew Wilner: And of course, well, it's important to protect all of the subjects, but it's also important to get the research done so that people can get the optimal care.
Dr. Jennifer Flint: Yes. absolutely.
Dr. Andrew Wilner: Does the TXA kind of wash out of the system? So if a week later, you need to give the patient heparin or there's some other issue, like you mentioned DVT, it's all ancient history by the time those problems come around?
Dr. Jennifer Flint: Yeah. So the protocols for TXA and trauma call for a bolus dose that you run over 10 minutes. And then you run another eight-hour infusion. And so it's really just during the duration of that critical time period, right after a traumatic injury where they're at highest risk for bleeding. And so by that eight hours, your infusion is done. And then, you know, it clears from your systems. And if you needed to anticoagulate someone later on down the road for that, it would not interfere with that.
Dr. Andrew Wilner: You know, if you could sort of have a seminar for first responders about TXA, what would be your take-home message?
Dr. Jennifer Flint: So my take-home message is think about it and think about it early. If you have a patient, even a pediatric patient who has suffered a traumatic injury and they meet criteria, which a systolic blood pressure of less than 80 if you're five years or less, if your systolic blood pressure is less than 90 and you're older than five, or if you're hypotensive or not responding to a fluid bolus, or if you have obvious bleeding, if you come upon a scene and you have obvious bleeding, they're a candidate for TXA. If they're greater than 12 or they look an adult, give the adult dosing 1 gram IV over 10 minutes followed by a gram over eight hours, and we'll continue that when you get into the hospital. If they're less than 12, use how you estimate a child's weight in the field per your protocol, 15 per kilo over 10 minutes is the bolus dose. If you get that started, that is awesome. And then we would continue the infusion once they get to us at the hospital.
Dr. Andrew Wilner: Oh, that's fantastic. This has really been very informative, Dr. Flint. Is there anything else you'd like to tell our listeners before we conclude?
Dr. Jennifer Flint: I think it's really important, if your team is interested in coming up with a TXA protocol, to get with your local trauma center, your pediatric trauma center, and just make sure that you're on the same page, that everybody agrees on the dose and the criteria for administering it. And just make sure that your trauma center is supportive and that everyone agrees on the protocol that your team is considering implementing.
Dr. Andrew Wilner: Well, thanks very much, Dr. Flint. This has been a very informative discussion. Thanks for joining me on Pediatrics in Practice.
Dr. Jennifer Flint: Thank you very much. This was a great discussion today.
Dr. Andrew Wilner: This has been Pediatrics In Practice with Children's Mercy, Kansas City. Please remember to subscribe, rate and review this podcast and all the other Children's Mercy podcasts. To learn more, visit childrensmercy.org/ems. I'm your host, Dr. Andrew Wilner. Thanks for listening,