So our next presenter will be, yeah, Michael. Just out of curiosity, how many folks here hold the prophylaxis when they remove JP drain? Anybody? How about a ventriculostomy when you remove a ventriculostomy? Right. So some of these are very practical elements that are not really covered in the literature. You know, where do I see hemorrhages? I see hemorrhages sub-gallially when the, you know, it's like the patient gets the triple whammy. They get the dose of Lovenox that we weren't aware of. They get the JP drain changed, or pulled rather, and then they get transferred out of the ICU or stepped down. So they're on the floor. So it's the perfect storm of events. They get this big hemorrhage that occurs unwitnessed while they're getting their DVT prophylaxis at the same time. The other area where we see this is with ventriculostomies and tract hemorrhages that form. We had initially done an analysis back in Philadelphia back about 20 years ago in 1997, 22 years ago now, where we looked at what was the effect of putting ventriculostomies in in patients who were coiled. Well, the key was that we put the ventriculostomy in before the coiling, and that was what changed our approach. Because otherwise, if they have hydrocephalus, you do the coiling from a subarachnoid hemorrhage, and then you want to put your ventriculostomy in, you found that they had a higher incidence of tract hemorrhages associated with that. That's right. That's right. Sure. Yeah, absolutely. Yeah, we'll go ahead and move this up. Well, good morning. Being the last speaker, it's going to be hard to say anything that hasn't been said up until now. When I talked to Rocco before this breakfast seminar, I said this is going to be one of those seminars that's going to be long on talk and short on data. And I think that you've seen that in the problems with meta-analysis and with guidelines, is that they're based on the available scientific literature, which is pretty sparse, admittedly. So let's see if I can come up with any different or novel observations. I have no relevant conflicts for this talk. So I'll start with a case. I like Randy's case, so I have a case, too. This is from civilian practice, a 54-year-old gentleman with multiple comorbidities. He presented to the ER with the worst headache of his life. He was walking into a gym around 5 p.m. and developed a headache. Now, what he was doing in the gym is he was watching his son in a wrestling match. The headache became more severe, so he did the natural thing. He ignored it and continued to watch the wrestling match. Finally, after the headache had been going on for about an hour, his wife convinced him to come to the emergency room. At that time, he had headache, neck pain. He had no other neurologic complaints, and there was no family history of aneurysm. The patient did, however, have a previous history of a left lower limb DVT and a pulmonary embolism from that. And he was apparently followed by the vascular surgery service at our institution, and he had been on Coumadin for over a year. This is a fairly recent case. His BMI was 47.3. That will give you the idea, the sort of spine patients I operate on, whether or not it's minimally invasive. And he was neurologically intact. Okay, so here's the CAT scan, and you can go ahead and look at the CTA, but Randy and Rocco, we have some experts here. Looking at that CT scan, does this look like an aneurysmal hemorrhage to you? Yeah, that was our sense is that, you know, it's not a typical aneurysmal picture. It's most likely going to be one of these folks that you're going to arteriogram up front. You're going to have a negative arteriogram, and then according to the literature in your practice, you're going to keep them in the hospital for 10 to 14 days and repeat that angiogram. You can also look for other sources of hemorrhage, like spine MRI for spinal AVM, but that's what we did, and it was negative. So what do we do with this guy? He is a picture of a, he's got like the stamp, I am going to get a VTE on his forehead. And he's had one negative arteriogram. He's had a previous VTE, and he's had a pulmonary embolism. So what do we do? Well, yeah, we probably should get another arteriogram, but in the interim, what are you going to do with this guy? You're going to put an IVC filter in him. We already talked about that. The potential complications, probably around 5%. A couple of things that weren't mentioned was, you know, you can clot off your IVC, go into renal failure and lose your kidneys, and that's been reported with IVCs. And also, they go on to chronic venous stasis changes, which can lead to amputations in the worst cases. So, I mean, that's not a benign procedure to do that. What we need, as our old friend Huey Lewis would say, is we need a new drug, okay? The problem is, you want a drug that's going to prevent clot formation where it's bad, i.e. below your umbilicus, but you want it not to prevent clot formation, or in fact, promote clot lysis up in the brain, right? We need a new drug. It's complicated, and I think that's going to be the theme of this talk here. In looking at the literature for this, I came across Virco's triad, and I was harkening back a lot to medical school days in preparing this, but this is the risk factors for deep venous thrombosis. Endothelial damage, and you can see there, smoking, hypertension, surgery, PICC lines, trauma. Hypercoagulability. Now, I am going to talk a little bit about precision medicine and genomics towards the end of this, and it turns out that if you're doing genomic screening on your patients, which I doubt anybody is doing, I'm certainly not doing it, that there's only a few known genes with risk factor for hypercoagulability. Factor V Leiden, prothrombin G20210A, protein C, and protein S deficiency. So there's really only about five or six that have been reported in the literature to date. And then acquired hypercoagulability, which we have to deal with a fair amount in neurosurgery with regards to metastatic cancer, folks on chemotherapy, pregnancy, obesity, and heparin-induced thrombocytopenia. And then finally, immobility and polycythemia in the stasis well. It's already been mentioned that we know neurosurgery patients have a high rate if they're not prophylaxed at all, and there's a reference for that one. Okay. This is another thing that harkens me back to medical school, and there will be a test on this, so you guys all need to know this, right? You're neurosurgeons. You're supposed to know all this stuff. If for no other reason than you're neurosurgeons, and if it's hard, you can do it, right? It turns out I went to Wayne State University's medical school in Detroit, and the professor of physiology when I was there was a fellow by the name of Walter Seeger, who very nearly won the Nobel Prize for his work on characterizing the thrombin molecule. That was kind of the state of the art back in the 70s, and now you can see he actually, when you're the professor and you're close to getting a Nobel Prize, what do you do? You build the department around yourself, and you hire all this young faculty to come in that are what? They're blood guys and girls, and they're coagulation people, so a lot of this coagulation cascade that you see out here was actually worked out at Wayne State's Department of Physiology back in the day. You'll remember that there's basically two pathways to activate thrombus formation, and then nature has evolved feedback loops here to actually limit that thrombus formation because you don't want it to go on indefinitely. The body would not do well if you triggered a thrombotic event once and it never stopped, so you have to have that, and there's the protein C, which can block some of these cascades here. And then you can see the, this is kind of a cool slide, which you can either get on Google Images or you can just take a picture of it right now, because it shows you the levels of all the activities of the various rat poisons that are out there today that we have to deal with as surgeons and where they actually work in the clotting cascade. This is kind of a neat picture here. If you look at the bottom panel, it reminds us that there is an antithrombin complex, again, that's evolved naturally to limit this process, but it also shows you in addition to the chemical cascade that's involved in forming clots, platelets are also involved, and we have, in order for a platelet to work, you know, again, the evolution of our knowledge, back when I was going to med school, the platelets just showed up, right, and they got enmeshed, and that was cool. But no, it turns out the platelets don't just show up, they have to be activated to do their thing, and they are working out the chemical pathways to actually show how platelets are activated. Why? Because you can interdict that activation and have these antiplatelet therapies that our cardiology colleagues are so enamored of. When we look at VTE, there's a professor of hematology at Chai University by the name of Doyeon Oh, who gives a really nice talk. I would suggest if we ever do one of these things again, we probably ought to invite him to come over and educate us about exactly the precision medicine. What's the goal? The goal is to take everything we know about the basic science, about epidemiology of VTE, and apply it in a precise way to an individualized patient. For this patient on this day, with this set of conditions, what do I do? Okay. It turns out that you can assess risk by a group or by the individual. The advantage of looking at groups is it's simple to do. You don't take into account individual variants. The evidence, which has been collected and been shown in the earlier talks, is strong. And an example of that would be orthopedic surgery procedures. And we have some pretty good guidelines on what to do given elective orthopedic surgery or even non-elective. However, when you're trying to apply that information to the individual, there are individual risk factors that contribute to the variability of VTE rates. When you pool them all together, that kind of averages out, right? But if I'm treating a single patient, there's a whole, beyond just the genetic and genomic factors, which I said, you know, there's only a handful of those, but lifestyle factors. You know, is this person a smoker? Is this person obese? So there are a number of factors that have to be taken into account if we want to apply precision medicine to the question of VTE prophylaxis in neurosurgical patients. We can try to risk stratify groups of patients, and this has been done. Low, moderate, high risk, the highest risks, and the higher your risk, of course, the more likely you are to have a DVT. And there's been a bunch of these things. Probably one of the most common ones out there is the Caprini score, which is over on the far right-hand panel there. And what are we looking in these things? We're looking like, oh, things like age, minor surgery. Is there a family history of thrombosis? Is there a malignancy? Are we doing something in the lower limbs? Is there a paralysis involved? You total up the risk factor, the higher your score. You total up those points, the higher your score, the more likely you are to have a DVT. And so we see the evolution in the panel on this side from when Caprini published the stratification scheme in 2005, now down to the most recent one, APEX 2014. So that's pretty helpful, isn't it? No. I mean, I can walk in a room and size up a patient and say, you know, this patient is at high risk for DVT. First of all, he or she is a neurosurgical patient. That means probably 30% right there. And then we could try to narrow it down a little bit more. Is it acceptable to do nothing in the case where your risk may be 30% of something bad happening? Probably not a good idea. So I think we've beaten the idea of risk factors. This is one scheme that was published in CHEST in 2012. If folks are high risk, Caprini score greater than 5, you probably want to use heparin to prophylaxe them. Moderate risk, heparin, very low risk. Maybe think about the intermittent and pneumatic compression devices. The reason those are safe to use in neurosurgical patients, you know why, right? Because they don't do anything. I mean, come on. You put those on people. If you can put people on heparin, put an IVC filter in, and they still throw a PE and a fairly major one through all that. What do you think compression stockings are going to do? And the guidelines have already been talked about, so I'm not going to belabor that. But it's based on, you know, these are Level 3 recommendations. And we've had the author here, Dr. Sorensen, gave an excellent summary of an excellent paper. It's a good frame of reference for kind of the state of the art of the literature now. And I think he summarized it very well of what's known and what isn't known. Another paper that just came out in neurosurgery, Agarwal et al, this is an interesting paper from Pittsburgh and it's out of the University of Pittsburgh and Allegheny General. What they did is they set up a VTE prevention protocol. And in their protocol, they enrolled prospectively 11,436 patients undergoing a neurosurgical procedure over a 24-month period. The protocol was 5000 IU sub-Q heparin Q8 on POD 1 for spine, POD 2 for cranial procedures, and by POD 4 for subdural, intracerabral, and epidural hematoma cases. And then they looked at the incidence of VTE and bleeding complications. So the incidence of bleeding complications is in orange on that bar graph there and the percent VTE is in blue. And what you see is the highest incidence of VTE, over 6% is in the open cerebral vascular and the deformity spine surgery. The next highest would be the traumas or strokes, intracerebral, subdural, or epidural hematomas. And you'll notice that the percent bleeding was unquestionably highest in that latter group as well, the intracerebral, hematoma, subdural, epidural. So in the very people that have a reasonable about a 3% risk for DVT, they also have about a 3.5% risk of bleeding if you prophylax them with this particular protocol. Okay, this is a good study and I think it kind of takes us into the direction of where we need to be going with these things. But a caveat, what's wrong with this study? And it was actually published in neurosurgery so they published the critical review along with it. And that is, there's no comparison group, okay? Historical comparisons may or may not be useful, but again, as Jamie put it, you know, it's not pure science. And therefore, the conclusions are subject to question. I think a lot of what you see in practice is observer effect. And I would urge you, if you take one thing away from this breakfast seminar, is number one, your neurosurgeons and your patients are at risk for DVT. And number two, look at it in your institution, know your numbers, and have a protocol. You know, what protocol at this point in time you've seen the state of the art, any protocol, pick one. Pick your own poison based on, you know, these numbers right here. Understanding that the safer you make your prophylaxis, the less likely it is to prevent DVT. But I think if you do that, if you even just go back to your institutions and start collecting, like how many procedures you did and how many of those people had a DVT, you will have a beneficial observer effect. I'm just going to go out on a limb and say that. This is kind of an interesting statement I found from, again, hematologists that tried to address what I thought was going to be one of the keys of this breakfast seminar. And this is a quote from the paper. The potential of genomics to advance medicine will require the integration of personal data obtained in the patient history. Environmental exposures, diet, social data, et cetera. Furthermore, without the ritual of obtaining this information, we will have depersonalized medicine which lacks the precision needed for the research required to eventually incorporate genomics into routine, optimal, and value-added clinical care. So, again, if you think there's a magic bullet that you can do some genomic test on your patient without looking into their, you know, their social history. And, again, some of the things we talked about, do they smoke? The state of the art just isn't there. It's not going to help you right now. Some final thoughts, and then we'll open it up to what I hope will be a very lively discussion because we're long on talk and short on data. It's complicated. Hit was only mentioned once, but it turns out that's 1 to 5% of folks clinically significant hit. 1 to 5% of folks that you put on trauma therapy, according to this paper by Ahmed and colleagues. Technology may help. That's a, that's what we're all hoping and praying for. For example, there's just a paper that came out two weeks ago in Science Translational Medicine where the group, a group at Harvard headed up by Alana Laura, Ana Laura Papa, who's been working on exactly this question, on trying to get something that will clot where we want it to and not clot where we don't want it to. In about a decade, she's come up with these bioengineered platelets where they've actually been able to modify some of those surface molecules that I showed you back on that cartoon a few slides ago and tease them into doing half of the problem. She hasn't, she hasn't solved it all the way, but I think if anybody's on the right trail by my kind of very superficial knowledge of this area of science, I think her group is doing some great work and I would recommend that you look that up, Papa A-L, and have a look at what's being done. And then the final thing is, and Randy talked about this a little bit, is the application of big data to solve some of these problems for you. Versus experience, and that's been kind of a theme in this AANS meeting this year. Several of the sessions that I've been part of, we're talking of experience versus big data mining. My observations on that. First of all, personal experience. You're looking at a guy that is now in his 30th, about to finish his 30th year of practice of neurosurgery. So I finished my residency in 1989. Conservatively, I've probably seen anywhere between 1,500 and 3,000 of these high-risk cranial problems or polytrauma problems in which, you know, the question of what do we do about anticoagulation has come up. And so what do I have to say about it? I don't know. Why don't I know? A couple of things. I wasn't keeping track of that for 30 years, right? You know, it's like the old joke, you know. The guy wakes up and he's 70 years old and he says, if I thought I was going to live this long, I'd have taken better care of myself. You know, if I thought that 30 years from when I started people would care about, you know, my experience, I'd have probably, you know, taken better care of that data. But I didn't. So, you know, along with that experience is coming lapses of memory, right? So that's a problem with experience. Secondly, I am not practicing anywhere near the same way I was 30 years ago. So that's a limited benefit. I would submit to you that there is not a single procedure that I do today that I do the same way that I did when I finished my residency. You try to get better. You come to meetings, you try to find out what the latest is and incorporate that into your practice. So your practice is evolving, okay? Okay, contrast that to big data to answer the questions. Jeff Manley's track TBI in traumatic brain injury I think is a great idea of this. We're collecting, you know, something like just a ridiculous amount of data points. 1,200, 3,000 data points per patient with tens of thousands of patients in the data bank. And then using artificial intelligence programs to actually mine that data. Now I'm old enough to remember that if you tried to submit a grant to the NIH with this 20 years ago, they'd say, oh, you're on a fishing expedition. We're not going to fund this. But, you know, things evolve. Things get better. And it turns out this is probably going to be a really valid way to tease out some more information so that we can take this pooled data, build algorithms without any preset hypothesis and pick out, you know, out of let's say 30,000 traumatic brain injured patients, we can pick out a core cohort that looks like the patient you're treating today. What happened with those 3,000 patients and how can you apply that information to your individual patient? And I think that day is coming. Okay. But it takes enormous amounts of resources to be able to do this kind of information. Enormous amounts of money. And then beware how that data is collected. You know, one of two ways. Some poor little somebody is going to have to sit there and click away at the computer and enter those fields for you. Okay. Especially when we're talking about laboratory data and geographic data, CT data. All right. What's the alternative? Automated data collection. Oh, that's a good one. We just heard how many in another session yesterday, how many charts nowadays which are computerized and would be reasonably easier to collect this massive amount of data are cut and paste. So if you are relying on automated data collection of cut and paste information over time, I would submit to you that your conclusions are going to be dangerously flawed. Again, it's complicated. It was a very great honor to share the breakfast seminar this morning with my colleagues and I want to thank you. And let's open it up to some discussion. Thank you very much.

VTE prophylaxis

neurosurgery patients

hemorrhages during procedures

risk stratification

genomics and precision medicine

big data in clinical questions