We're moving on to the next speaker. I would ask Dr. Muschlin, please, to come up and report on traumatic intracranial hemorrhage in the setting of four-factor PCC. My name is Harry Muschlin. I'm a PGY-5 at University of Maryland School of Medicine. And this work was done using patients through the Shock Trauma Center in Baltimore. I have no disclosures. The coagulation cascade, as we know, has an intrinsic and extrinsic pathway that allows particular drugs to target different clotting factors that can put you in an anticoagulated state. Warfarin is going to target 2, 7, 9, and 10. And then we have the new novel oral anticoagulants, or NOACs. They're going to target 10A and 2A. In trauma patients also, a hypocoagulable state is from a multifactorial system. And so there's not one reason why these people are at risk for bleeding. But overall, a combination of being a patient on oral anticoagulation and being a TBI patient makes you a difficult trauma patient to treat from a coagulation standpoint. So when I was an intern, which is that me, our INR levels were what we would target for patients that would come in who were hypocoagulable, particularly in a Warfarin state. Now, we had fresh frozen plasma was the standard. And that gives you all the clotting factors. There's known risks, though, volume being one of the main ones, 200 to 250 cc's per unit. People at cardiac risk who are already cardiac patients usually from being volume overloaded. You have to thaw the FFFP. It takes longer to give it. And the ability to reverse. Anecdotally, I feel like we all have a different experience, perhaps, of what you can get to. But a lot of times, the ICU will give you pushbacks saying, we can't get below 1.5. So then no more FFP is given. And then vitamin K is another method, but that's slower and induces clotting factors from the liver, but it's not an immediate fix. So Kcentra is a 4-PCC product, or a prothrombin complex concentrate, approved by the FDA in 2013 for Warfarin reversal. It did have a longer use in Europe before it was approved here. It has 2, 7, 9, and 10. It is also derived from human plasma. Because it's a concentrated form, though, it's 1 to 10 cc's for FFP. So it has a much smaller volume, which is critical. Smaller volume, it also can be delivered more quickly. And so faster reversal times, 4 and 1 half times faster on some studies. And it can be measured 10 to 30 minutes after administration. Anecdotally, I'll tell you that in our system, I'm getting these almost immediately after as well. So safety profile compared to FFP. Hinckley et al. in 2014 had an ER patients and showed a half reduction in serious adverse events compared to Kcentra versus FFP. So in the traumatic side of usage, it's really been small sample size in literature, which kind of drove me to do this project. Sample sizes in 2013, there were seven subdurals that were reported in the setting PCC, but it was treated with a three PCC, not the four PCC. So only three may clotting factors. 2014, there were two patients in a study. Frontera et al. is more the common paper that's cited for Kcentra use. And there were 19 subdurals, but it was very unclear if any of them were traumatic. And they did exclude all other traumatic bleeds, so it was unclear if these were spontaneous or not. Probably a mixed bag, but still don't know. And then in 2015, there was eight patients. So you kind of get the gist. That's a small sample size. Hemorrhagic expansion or recurrence rates were also small, 10 to 66%, so a varied amount. Frontera et al. did show that PCC groups had significantly less than FFP group in 2014. Now, thromboembolic events, about zero to 10%. And then limited use with NOACs. They're more common, of course, to be on Warfarin, but nowadays, in our clinical setting, we'll see more and more people on a NOAC. And so this has been varied in terms of the literature as well, how much data we have or experience. 2015, all neurosurgical patients on NOACs, but only eight were TBI. In 2017, Melmed et al. had nine NOAC patients, but only one was treated with a PCC. And then there was a very large German study, multiple institutions, 146 patients, but they were all spontaneous ICHs, so they had no trauma. So at Shock Trauma, we did a retrospective review. We just wanted to look at coagulopathies, and I divided them between Warfarin and TBI and NOAC patients. Treated with Kcentra, they had to have a intracranial hemorrhage. I wanted two CTs within, at least two CTs within 72 hours, and 44 patients were identified. The demographics, majority were male at 72%. Reason they were on anticoagulation, majority were AFib, and their emission INR mean was 2.34. Warfarin was the most common medication. Only had five NOAC patients. Most commonly was an acute subdural at 38%. Pre and post Kcentra INR, overall 2.4 to 1.3, which was significant. Warfarin group had a reduced from 2.5 to 1.3, and the other group, or TBI and NOAC coagulopathy, went from two to 1.4. Now, secondary endpoint was looking at hemorrhagic progression or recurrence. I did find that of the whole group, 17 patients, or 38%, had progression or recurrence of their bleed. And no other of these factors were significant. Either type of coagulation didn't matter. And the bleed type was nearing significance with the most common type of bleed that grew or recurred was an acute subdural. And we looked at disposition, home, rehab, or death. And in this group, we found that, even though it was a small number, it came up significant, that all people who had a history of stroke died, and that if you had hemorrhagic expansion at any point or recurrence, no one went home. You either went to rehab or died. And then, as expected, your admission GCS did predict where you would go for Dyspo. And just to report our experience with the thromboembolic events, we had eight patients, or around 18%, seven DVTs and one PE. Conclusion, I think K-Center is a safe and effective and better alternative to FFP for reversal of INR, even in the trauma setting. We can, even though the data is still small, even with my study, I think it's probably worthwhile to use in a TBI patient who's coagulopathic or a NOAC patient or the combination of above. All these patients are TBI patients in addition to having anticoagulation. And then, it just stresses the importance of preventing hemorrhagic progression or recurrence as none of the patients were able to go home who had this event. Those are my references, and thank you. Thank you.

traumatic intracranial hemorrhage

four-factor PCC

coagulation cascade

anticoagulation medications

Kcentra