Hello, everyone. My name is Ryan Kitagawa. I'm the Director of Neurotrauma for UT Houston and Memorial Hermann Hospital, and today we're going to be talking about VTE prophylaxis, clinical practices and guidelines. So I have no disclosures. So across this session, you'll hear multiple speakers. I am specifically going to be talking about venous thromboembolism practice guidelines. I'm going to stay a little bit away from the literature and the advances because you'll hear about that later on, and I'm going to try to keep it generally broad. So if you look at my training, how things have developed in my residency 15 years ago, at that time, we didn't do any chemoprophylaxis. We used TEDS and SCDs only, sort of your traditional compression devices. Over the course of my residency going into my fellowship, we became much more comfortable with DVT chemoprophylaxis. Most of the time we started it within 24 to 48 hours, but we were still not okay with things like aspirin or feral anticoagulation. But now in my current practice, we are very aggressive in DMT chemoprophylaxis, and at the end of the talk, I'll actually address some of the things with aspirin and anticoagulation because if we're more comfortable with that, then our level of comfort with traditional DVT chemoprophylaxis should be more. So the biggest problem, when is it safe to start or restart antiplatelets or anticoagulants after traumatic intracranial hemorrhage? The main purpose of this talk is to talk about DVT chemoprophylaxis, but we'll also talk about aspirin as well as ibuprofen and anticoagulations along the way. So we look at these cases. These are different diseases in traumatic brain injury. You have the subarachnoid hemorrhage, epidural hematoma, contusions, and acute and chronic subdural hematomas. These all behave very, very differently, and therefore we have to kind of guide our clinical practice based on these different diseases. And we also need to look at other things other than traumatic brain injury in terms of our neurosurgical practice. Now, what patient population is at risk for developing DVTs and PEs? Well, if you look at the literature, intensive care unit patients, cancer, stroke, pregnancy, and most important for us, those that are immobile, whether it be traumatic brain injury, spinal cord injury, orthopedics, traumas, or in our case, post-operative patients. These patients are definitely an at-risk population. There's a lot of different scoring systems out there to kind of rate how risky chemoprophylaxis is, how urgent it is. In my practice, quite frankly, I'm not doing risk stratification and risk scores. In my practice, everybody gets DVT chemoprophylaxis. It's how soon after their trauma or how soon after their surgical procedure do we actually do it. So in my practice, immediately upon admission, everyone gets pneumatic compression devices, unless there's obvious open wounds on their legs or they have a DVT in that arm or lymphedema in one location, I'm starting pneumatic compression devices. 24 hours after stability scan, if surgery is not imminent in my traumatic brain injury patients, or 24 hours after their surgery for pretty much all comers. Most patients I use sub-q heparin in your standard TBI or your, for example, awake and alert spine patient or elective cranial surgeries where they're doing quite well. For those that are high risk, immobile, severe TBI, you know, I tend to use enoxaparin at the high-risk dose. I don't stop the sub-q heparin for LPs, lumbar drains, ventriculostomies, or drain removals. In your post-op craniotomy patient who I start them on their DVT chemoprophylaxis, they need the drain in for a few extra days because of high output. I have no hesitation in keeping the sub-q heparin with the drain removal. If a patient unexpectedly later in their hospitalization requires ventriculostomy or an ISP monitor placement, I will hold one dose if it's possible. If it's not possible, I'm just going to proceed forward with the intervention. I'm not going to reverse with something like protamine. I just will treat them as they are. So in these patients, both your traumatic brain injury patients and your post-surgical patients, we have to have a rational approach to these blood thinners because these are many different diseases that we tend to treat as one disease, and so we have to think about it in a rational way. So in high-risk lesions, contusions, surgical lesions, mass effects, complex surgeries, lots of blood loss, tenuous hemostasis, those are the ones that the risk of hemorrhage is high and we tend to delay their chemoprophylaxis a little bit longer. Low-risk patients, a post-traumatic subarachnoid hemorrhage patient, post-traumatic IVH patient, DAI, routine surgery, you know, a routine spine surgery, those are ones that are fairly low risk for hemorrhage and that we can really plan to start them relatively early. And then, of course, the risk for thrombosis. If they're immobile, have cancer, have a hypercoagulant state, those are the ones that we need to be starting them on DVT chemoprophylaxis relatively quickly. You know, the lower issues, those that are going to be relatively mobile, those are the ones that we can wait a little bit longer. And so we need to have a rational approach to how we do these blood thinners. So, for example, you know, a patient who has an elective lumbar disc removed, okay, that patient is going to be ambulatory. It's a relatively low risk of thrombosis. They're probably, frankly, either going to go home from the recovery room or go home the next day. Those are the ones where, you know, I tend to delay a little bit longer. If they're just going to go home the next day, I don't necessarily have to start it. You know, versus a patient who, for example, a traumatic brain injury patient who's comatose, who's immobile, those are the ones where I want to be a little more aggressive along the way in terms of treating them. So, you know, the point of my talk also is to talk about the guidelines. And it turns out the guidelines are very challenging. They really don't have a great influence over our clinical practice. So, if you look at the American Society of Hematology, for medically ill patients, hemoprophylaxis is favored over mechanical. The injectables, low molecular weight heparin and unfractionated heparin are favored over oral medications. They suggest enoxaparin. They do not recommend it for extended outpatient therapy, meaning after the patient's discharge, they should not necessarily be on that constantly. But this doesn't give us any good guidance on what do we do for traumatic brain injury patients, how soon do we start it, not good guidance for us to really be able to influence our clinical practice. So, we look at the European guidelines for perioperative period. And again, these are really, don't guide us very much into how we deal with these things on a day-to-day basis. So, for someone with a craniotomy, they recommend pneumatic compression and low molecular weight heparin when the risk of bleeding is presumed to be decreased. What does that mean? How does that influence our practice? For hypertensive hemorrhages, when the breeding list is presumed to be low. For spinal surgery, if there's no risk factors, then it doesn't necessarily need thromboprophylaxis. For those with higher risk factors, they recommend giving it when the risk of bleeding is presumed to be decreased. Well, what do we do with that information? How does that actually influence our clinical practice other than to say that they should be on it? So, what are some other guidelines? So, the CNS, insufficient evidence, but they are recommended. Routine screening for DVTs are not recommended, but when do we give it? How do we judge that? North American Spine Society, not always needed for elective cases in the ambulatory patient. Pneumatic compression devices are recommended when needed, and chemoprophylaxis should be used cautiously for high-risk hemorrhage patients. Again, doesn't really help us guide our day-to-day therapies, and the AHA recommends it for high-risk patients, especially brain tumors, but again, doesn't give us good guidance on when to start it. So, that's what we're here for. So, the most helpful, in my opinion, is the Neurocritical Care Society. So, in just your standard ischemic patients, pneumatic compression devices and low molecular weight heparin immediately after the stroke has occurred. For intracranial hemorrhages, pneumatic compression devices immediately, unfractionated heparin or low molecular weight heparin within about 48 hours. Aneurysm rupture, about 24 hours after the aneurysm is secured. And traumatic brain injury, pneumatic compression within 24 hours of the TBI or their craniotomy, and then chemoprophylaxis within 24 to 48 hours. Brain tumors, if they're non-surgical, both interventions right away. If they are surgical, then it becomes a lot more complex of a challenge. For spinal cord injury, they recommend within 72 hours or as soon as the bleeding is controlled. They recommend against just using pneumatic compression devices alone without some sort of chemoprophylaxis. In elective spine, no unless the intervention is considered to be elevated risk. In complex spine, which you should be getting an entire lecture on, they recommend both pneumatic compression devices and chemoprophylaxis. However, they do not recommend prophylactic IVC filters. And for elective craniotomies, chemoprophylaxis and pneumatic compression devices within 24 hours. So how do we synthesize all of this information? Well, I think that as soon as it is possible in your clinical practice and your level of comfort is when you should be doing these. In my practice, pretty much every patient who's not going to be discharged the next day gets chemoprophylaxis. In my opinion, even if the patient is ambulatory, a mild TBI, those sorts of things, when you're in the hospital, you're not as mobile as you are at home. You get up, you move around maybe two, three times a day, as opposed to our regular lives where we're constantly mobile. So I think that chemoprophylaxis in that stressed situation is appropriate. I think DVT chemoprophylaxis is indicated in all patients when they are safe. And what I personally feel are safe is 90, 95% of patients, 24 hours post-op after their surgeries, unless there's something I'm specifically concerned about, or stability head CT after a trauma. In the majority of my head trauma patients, I will repeat a scan at four to six hours after their trauma. If that head CT is stable, 24 hours after that, I'm starting them on sub-q heparin. If it's just an isolated mild TBI, anoxaparin for the overwhelming majority of those other patients along the way. If it's a tiny little traumatic subarachnoid hemorrhage, it's stable on scan, less than 24 hours, perfectly fine. If there are contusions that are blossoming, sometimes you have to wait closer to 36 hours, but in general, 24 hours is fine. And I only stop DVT chemoprophylaxis for active bleeding or major surgical interventions. And that's something that has changed over the years. And so the reason I've developed my practice in this way is that some of my experience with aspirin and full dose anticoagulation have sort of guided me to realize that it's not as dangerous as we would expect. This is a deviation from the topic at hand, but I think it is important because if we're comfortable in this, then clearly DVT chemoprophylaxis is something we should be comfortable with as well. So we take our same TBI patients. Okay. When do you start DVT chemoprophylaxis? When do you start aspirin? When do you start IV heparin? I can tell you in every one of these patients, 24 hours after stable scan, I'm starting them on DVT chemoprophylaxis. Simple, straightforward, very low risk. But what do we do about aspirin? And what do we do about IV heparin? So the literature out there is minimal. The current recommendation from the American Heart Association is to hold all blood thinning agents for a minimum of two weeks after a head injury. There is a lot of patients where we don't have that time to wait. You know, a patient who has a cardiac stent in that was placed two weeks ago, they fell, hit their head, had a hemorrhage. We're not going to wait two weeks to restart aspirin or potentially clopidogrel on those patients. So how do we define the outcome? Okay. Well, we got to look at several things. We've got to look at radiographic progression, meaning that the hemorrhage is worse on the scan, but the patient is fine after we started these agents. The clinical decline, did we start aspirin? The patient had a hemorrhage, got worse, had to require some sort of intervention. We also need to look at delayed complications. You know, a patient with a traumatic subdural hematoma who does not require a surgical intervention, comes back with a chronic, and we've already started them on aspirin. Is this our fault? Did we cause this to happen? Then we also have to look at the complications of not starting these medications. So the thromboembolic events, patient had a heart attack, a PE, or a stroke after their trauma that we could have prevented. What does it mean that we could have prevented? Well, perhaps we knew about their problems, their preexisting conditions that required blood thinners, or perhaps we knew that they had a blunt cerebral vascular injury, a carotid dissection. We didn't start them on the aspirin as we should have. They got the stroke. This is a potentially preventable event. So what is the natural history of subdural? So we understand what happens with the chronic subdural as well. The literature is very variable. In this particular study of a fairly large number of patients, it was about 15% of the time, a non-operative acute subdural hematoma turned into a operative chronic subdural hematoma. So we can judge our numbers based on that. So what is the data that we've published on this? So the use of antiplatelet agents after traumatic intracranial hemorrhage. Fairly large patient population, over 200 patients. About 40% of them, we started the aspirin because they had a previous history of it, or they had a condition that required it just from their general medical conditions. About 40% of the patients had some sort of dissection, carotid or vertebral, that required the antiplatelet agent. The median age was 61. The median GCS was pretty good in the mild range of 13, but over 20% of the patients in our patient population did require some sort of neurosurgical intervention, whether it be an ICP monitor or a craniotomy and open procedure. And so those are important patients for us to look at as well. So what were the results? So the median time of injury from time of injury to starting the medication was about four days. In my residency, where we didn't even use DVT chemoprophylaxis, that was unheard of to start it within four days. So what were the complications? One radiographic complication that did not require any intervention. Six clinical complications. Two of them were delayed hemorrhages along the way, 11 days and 14 days after starting the aspirin. And we do have to ask the question of, was it the aspirin that was the cause, or was this related to the patient's disease, given that it was so far out from the initiation? And four chronic subdural hematomas that require an evacuation, which is fairly consistent with the natural history. But what thrombotic events occurred in our patient population? Well, around 10% of them had some sort of heart attack or stroke or otherwise. With around 13 of those patients, we knew they had a problem that needed an antiplatelet agent that we didn't start it. Most commonly was the blunt cerebral vascular injury patient. We didn't start the aspirin because the intracranial hemorrhage patient had a stroke before we were able to initiate that. So no significant difference in age, GCS, ISS, or the time to start the medications. But if we look at the patient populations and when we started it, we start to see some trends along the way. So if you look at the blunt cerebral vascular injury patients here, days from injury to initiation of the aspirin was usually within seven days, with the highest being around three days afterwards, with very few complications as we see from our overall patient population. From those that had preexisting conditions that needed it, some of them same day, most of them up to a week afterwards with very few complications as well. The big question is the dangerous patients, the surgical patients. There's quite a few patients who we started it either almost the day of their surgery or within the first few days of their surgery. And there's patients with severe TBI where we're starting them on aspirin very, very close to their time of injury, usually for blunt cerebral vascular injury patients. What thromboembolic events occurred? Well, as we see from this, it's very early in the process, very early, and that's the reason why a more aggressive approach to these blood thinners is usually necessary. So what is the conclusions and what do I do for my practice? So if the patient is a low risk for heart health, okay, if they just are taking it for their own heart cardiac conditions, I'm very comfortable in waiting for the full two weeks as recommended by the American Heart Association. But if they're moderate risk, coronary artery disease, they have old stents in place to say something that they need it sooner rather than later, 72 hours to one week, perfectly fine. High risk patients, recent stents, BCVIs, 24 to 48 hours after stability CT. So our protocol is if a patient comes in with a traumatic intracranial hemorrhage with a standard, maybe a grade one blunt cerebral vascular injury patient injury, 24 hours after stability scan, they get their subcuhepin or their Lovenox. 48 hours after that, we start their aspirin, that sort of standard protocol. If the patient has a higher level of injury, a grade three injury, we'll start them within 24 hours without much concern. We start both their DVT chemoprophylaxis and their aspirin at 24 hours. And then the very high risk patients, for example, someone who's having an SC segment elevation MI, some of those we start immediately. My most recent recollection of a patient who came in with a STEMI and some traumatic subarachnoid hemorrhage, the patient had their scan. We watched them for about four to six hours, repeated the scan at four to six hours. The CT scan was stable. They went straight to the cath lab, got dual antiplatelet agents in a stent place without any complication along the way. What do we do about anticoagulants? Not just DVT chemoprophylaxis, but full anticoagulation. Well, we studied this as well. We had about a hundred patients. We had several patients who developed DVTs and PEs and required anticoagulation. Others resuming their previous medications or MIs where we had to start them on those anticoagulants. Median age of 54, around 28% of those patients had some sort of neurosurgical procedure prior to initiation of their anticoagulation. So this is a high risk patient group for bleeding. So the median time from injury to starting their anticoagulation was about a week. And the reason for this is that most of the DVTs and PEs did not develop until days later, and therefore they did not require their anticoagulation for days later. What complications did we see? Around 3% of the patients had some sort of increasing hemorrhage on their CT scan that did not have a clinical issue. Around four patients had some sort of non-neurological bleeding complication, like a GI bleed related to that. One patient developed a surgical chronic subdural hematoma. Again, fairly consistent with the natural history of this. We had one delayed acute hematoma that developed weeks after their anticoagulation. And in retrospect, it was actually a ruptured aneurysm that caused that hemorrhage in a delayed fashion. So it turns out that these really aren't as dangerous as we had suspected. So we have here the time from injury, the time from procedure, and the time from stability scan. And what you see is most of these patients are within a week to two weeks, but we do have a fair number of patients who are starting them on anticoagulation almost the day of, or two to three days afterwards. And these were the high, high risk patients along the way. So what is my practice? If they're low risk, just plain atrial fibrillation, I usually get a CT scan at follow up at two weeks and then start them on their anticoagulation at that point. Most of these patients, I will start them on an aspirin, you know, 48, 72 hours after their trauma, after their stability scan, and then treat them at follow up. You know, if someone has a known DVT or a history of PE, moderate risk, I'll usually wait, you know, a little bit shy of a week to start them on their heparin. For the very, very high risk patients, Factor V Leiden has a mechanical mitral valve, you know, 24 hours to 48 hours after their stability scan, I found is fairly safe and is consistent with this literature along the way. Much the same as I described in the antiplatelet, my most recent anticoagulant case that of course was very anxiety provoking, was a patient who had superior sagittal sinus thrombosis, had an intracranial hemorrhage, required a decompressive hemicraniectomy for the cerebral edema. The patient clearly requires anticoagulation, otherwise everything is going to get much, much worse. Knowing about that ahead of time helped me gauge my surgery, obtained outstanding hemostasis, very careful hemostasis throughout that. Within 12 hours of their craniotomy, they were on IV heparin. Within 12 to 18 hours after their surgery, they were fully therapeutic on their IV heparin without complications, something that, you know, 10, 15 years ago in my residency, I never would have even considered, but now we're finding that it's less dangerous than we expected. So what's our protocol? We use IV heparin without a bolus. When we reach our therapeutic goal, which in most patients is 60 to 80, we repeat the head CT. If the head CT is stable while therapeutic on the IV heparin, we transition them over to warfarin. You know, we do the IV heparin because it's very easy reversible within seconds, if it's protamine within hours, if you just want to turn it off. And that way, if there is a hemorrhage, we can catch it before it becomes clinically significant. And then if they're clinically stable over several days on IV heparin or on their Coumadin, we use sometimes we'll transition them over to enoxaparin or the novel anticoagulants. So in conclusion of all of this, as you can see, aspirin and IV heparin were less risky than what we thought. You still have to have a very rational approach to this. Don't start IV heparin on a patient who doesn't require it right away. Don't start it on patients who have extremely high risk intracranial lesions or extremely high risk surgeries that were done. But the risk of a problem is less than we thought. Aspirin is generally safe within 48 to 72 hours. Subq heparin or low molecular weight heparin for DVT chemoprophylaxis usually within 24 hours is very safe for pretty much all comers unless it's extremely high risk. And I hope this helps you gauge your clinical treatment. Thank you.

VTE prophylaxis

chemoprophylaxis

patient populations at risk

DVTs

PEs

clinical practice