it is my absolute pleasure to introduce if everyone have their seats, please introduce our keynote speaker. My wonderful friend and colleague dr Jeff Barnes from the university of michigan. Um I learned something new about you Jeff, I didn't know you study your a biomedical engineer. He trained, he did his undergraduate work at the universe at washoe in ST louis and biomedical engineering and then really has spent his entire medical career and training at the University of michigan and dr Barnes is a nationally known expert in anti coagulation. He is the co director of the michigan anti coagulation quality improvement initiative known as Mackey. He's an independently funded investigator and he's also a national leader in the vascular professional societies including service as a board member of the anti coagulation forum. He's also a wonderful friend to all of us in vascular medicines who were just excited to have you here Jeff and he is going to give our keynote address. Anti coagulation and VT management, what every vascular specialist must know. Let's give a round of applause and welcome to Dr Barnes. Well thank you so much, it's it's really an honor to be here both locally and heather. I want to thank you especially for this invite. I'm really touched to be asked to give this keynote but to all of you for welcoming a wolverine into this buckeye state, especially after what happened, you know a couple of weeks ago. Um I will say however I was actually born in the state of Ohio so I'm kind of used to this, my entire family like to give me a hard time. And so after 10 years, it's, it's nice to have a little something to celebrate. Although one of them did tell me that they think Ohio State let us win. So we'd re up Harbaugh's contract so they could win for the next nine years I think, you know, remains to be seen how all that plays out. I I, my daughter's in kindergarten, she hasn't learned those letters yet. We're working on some of the others right now. We'll see how that goes. So, I do have a couple of disclosures here that I want to make sure we know about for this talk. Let's see. Is this moving us forward? Um, it mostly relates to companies that either make anticoagulants or make different tools in the care of patients with venous thrombosis embolism. But I'm gonna try and uh, be a little bit above that today and really hit on a couple of key points around care of patients with VT. I think it's helpful to start with a clinical case. So, I want you to think for a minute about a 62 year old woman, she's presented to the emergency department with some chest pain shortness of breath. This has been going on for about six hours now, of course we're here in Cleveland. And so she told us that she recently came back on a flight from Miami and that got her concerned about what may be going on. This is a woman who's not just obese but has morbid obesity A. B. M. I. Of 42 she's got diabetes some chronic kidney disease and has hypertension along with that. And she's on some fairly typical medications that we would expect to see Now in the emergency department. She actually doesn't look that bad. Her heart rate is pretty normal, she's breathing at a comfortable rate, blood pressure looks good, she's actually saturating 94% on room air. They do some typical labs and they get a d dimmer and that dimmer is elevated creatinine is about 1.3 which is about baseline for her and her troponin is normal. You know, nobody gets into the er without a troponin of course, because of that elevated diner and her symptoms, they say let's go ahead and order that P E C. T. Scan and what they find is acute segmental and sub segmental pe in the right upper lobe. But with a normal sized right ventricle, so normal right ventricle to left ventricular ratio. So if we take a minute and we just stop here, there are a couple. I think important questions we can ask ourselves. This is a woman who has an acute pe, does she require admission for treatment? I think that's kind of the first question that many people would ask secondly, what would be the best anti coagulant that we could give her right now And then of course, once we've given somebody a diagnosis of DVD or pe and we start them on anti coagulation, we always ask ourselves, how long do they require anti coagulation for? So I'm going to try and answer those in about the next 15 or 20 minutes. Well, when we think about acute pE risk stratification right now, most of us are looking to the european Society of Cardiology guidelines. Those are really the most updated and probably the most comprehensive set of guidelines and how we approach these patients. I'm gonna walk you through this a little bit. The first thing we always ask ourselves is is this patient hemo dynamically unstable? Do they have a blood pressure? That's so low, we're worried about shock. Are they having such high oxygen requirements? That we think this person is having respiratory failure? If so this is a person in whom we would consider them to have high risk or massive pe that's a patient for whom we don't think about. A whole lot else. We immediately start going to what kinds of advanced therapies are needed in order to help prevent this person from getting any worse, thankfully. That's a small piece of the pie. So after that, once we know this person has normal human dynamics and the respiratory status isn't significantly altered. We then ask ourselves what's the risk that this person could decompensate in the next hours to days and that's where we look at things like the Pepsi or Spc risk scores and then we follow that up with certain other biomarkers, lab findings and imaging tests evidence of troponin elevation due to stress on the right ventricle, or objective evidence that the right ventricle is enlarged, either on a CT scan or an echo. When all of those are normal, then that's a person who's in the green zone, the low risk zone, and this is a group for whom we should actually be thinking about outpatient treatment of PE So, for our patient, when we think about her presentation, she had normal blood pressure, normal respiratory rate was not requiring supplemental oxygen. This is not a high risk patient. Furthermore, her Pepsi score is actually quite low. The only risk she actually gets is due to her age. So, this puts her in class one, the very low risk class for complications. Furthermore, Her echo and her proponents were both normal. I'm sorry, her CT scan and her proponents were both normal. So, this is somebody who does fall into that green zone or the low risk person. So we can think about home treatment for her. How do we know that's the case? Well, there's actually been a recent meta analysis done of a number of different studies saying that if we have a patient who's low risk for complications, can we treat them at home versus hospitalization and whether you look at the top set of figures, which is all cause mortality up to 12 months or the bottom set of figures, which is Evidence of recurrent pulmonary embolism up to 12 months. You see either a similar or favorable outcome for home based treatment. This has been further solidified in a recent trial called the Math V. T. E. Study just published this year. This was a study where they took patients both with DVT and PE. But I'm going to focus on the pE cohort here and they said if you meet these low risk criteria as well as a few other criteria that are er docs like to use, Could we treat you as an outpatient? And what they found is overwhelmingly fairly successful. In fact, of the 518 patients with pe that they treated as an outpatient, only seven had evidence of recurrent pe. That's a pretty low risk 1.4%. And furthermore, most of those had reasons for anti coagulation, non adherence, largely due to financial or prior off issues, some due to some issues around bleeding concerns or the patient just didn't fill the medication whatsoever. So if we can reliably anti coagulate someone that should even further um reassure us that this is an appropriate and safe strategy. Now, why is that the case? Well, this is sort of the way we think about anti coagulation in patients with acute and chronic venous thrombosis embolism right now, I actually want you to start on the bottom part of this figure. You know, anyone who trained in medicine 10 or more years ago, you know that the standard of care was to give a patient a parental anticoagulants. Either unfree action, ated Hepburn if they're being admitted or maybe a low molecular weight heparin. And then you use that as you bridge them over to warfarin therapy, a vitamin K antagonist. And that was really the only therapy option we had for literally decades Roughly. About 10 years ago. We have the introduction of what are now four different direct oral anticoagulants and in many ways they've been game changers. Now some of them have simply replaced Warfarin in that same care model, you still give a parental anticoagulants for anywhere from 5 to 10 days. And then you switch over to something like the big Atran orthodox even. But the real game change has happened on the top side of this figure where we now have oral only strategies, you can start somebody without any parental anticoagulants on oral rival rocks, Urban or oral Epics, Urban and treat them for the first 1 to 3 weeks with an intensified regiment. Let's make sure we stop that acute clotting process after that. You give them their primary treatment phase which lasts up to 3 to 6 months with our standard doses River rock salmon, 20 mg a day, a pixel man five mg twice a day. And then beyond that we have the option but we're not mandated to potentially even reduce the dose of both of those drugs in a secondary prevention or an extended treatment phase that goes out beyond that initial 3 to 6 months. And it's because of this oral only approach that we can really now think about strategies for implementing home based treatment of both DVT but also pe now you may ask how do I operationalize this and I really want to call attention to these starter packs. If you noticed on the last slide, there's this idea that we have to give an intensified regimen in the first 1 to 3 weeks and then we get to sort of our standard treatment doses that can be really confusing for patients especially if they're different strengths of the drugs. If there's different numbers of pills they have to take. So rather than writing multiple prescriptions that gets very confusing and people are taking from two bottles at once or maybe they're not taking any or maybe they're having to pay two copays, simply write a V. T. E. Starter pack for either river rocks Carbonara picks even. They'll get this great card that walks them through the first month and we'll tell them for each day of therapy which pills to take in the morning, which pills to take in the evening and it will automatically transition them if their arrival rocks even patient at day 22 they'll transition from the twice a day to the once a day therapy they don't have to think about it. They just have to follow the days in the card. The same is true if they're on a picks even when they go from day seven to day eight rather than doubling up the dose twice a day, they go to the standard dose twice a day. This is really a much easier way to treat patients with VT but please do not ever refill these. This is not for month 23 or four and do not use this for patients with atrial fibrillation. This is only for patients with acute venous thrombosis embolism. In that first month of treatment after that you just go with your standard prescriptions. Now you may ask me, I've heard that these drugs are great. I use them a lot. But aren't there patients in whom we should not be using them? Well, let's walk through a couple of those scenarios because I want to update you on a little bit of evidence. Um one of the most common risk factors for VT of course is obesity. We see this everywhere. Right. And is it safe to use a fixed dose drug in patients regardless of their body mass index or their body size. We now have some updated data to say perhaps we can this is data from five different U. S. Health claims databases. We're talking over 100,000 patients who had normal weight and even more than 20,000 patients are about 20,000 patients with morbid obesity GMS of greater than 40. And what you can see on the top which is the regular obesity. But the bottom in the red box, this is the morbid obese group. They actually have better outcomes when they're treated with a pixel band. And there's some similar data as well for uh River rocks even than when they get warfarin. So really we can see that recurrent VT. E major bleeding outcomes, even clinically relevant, non major bleeding outcomes are quite favorable. Even in these um these groups of patients who have B. M. I. Is greater than 40 weights greater than 120 kg. Now this is just one set of data but there's really actually a growing body of data to support this. It's not actually coming from the phase three studies, we have pretty limited data available in those randomized trials as you can see on the left side of this table. But on the right side of the top of the table, you'll see the phase four studies the real world data studies are showing similar outcomes in patients who have B. M. I. Greater than 40 with A picks even compared to those who have BMS of less than 40. Same for river rocks, urban and in general for do X as a whole. But we don't have as much data for the day bigotry and Orthodox open group. That's okay because almost all domestic use in the United States is both a pixel band and River rocks even so those are the two you're probably most familiar with the most comfortable with. In fact, this data has actually led to an updated guidance statement from the International society on thrombosis and homeostasis who say you can now use standard doses of a pixel bond or rival rocks even for patients with acute VT regardless of their waiter B. M. I. And importantly they said you no longer need to go and check those anti 10 A peak and trough levels which can be kind of cumbersome to get and we don't even know how well they correlate with clinical outcomes. So feel confident using these drugs. You might want to be a little bit more reserved if you're gonna use too big a train Orthodox man. Just because we don't have quite as much data there yet. But I wouldn't be surprised if that's coming soon now. What about the cancer patient you might say. But I've heard that we have to use low molecular weight heparin for cancer. That's really important. And yes you're right. Low molecular weight Heparin is better than warfarin. But we now have a number of studies. I'm only showing you the most recent one here showing that yes, it's actually safe to use the direct oral anticoagulants in patients who have cancer associated VT. We see similar and sometimes even better outcomes when we have both a pixel ban and we have multiple studies we have a study of river rocks even as well as compared to adult apparent which would be a low molecular weight heparin comparator. And so these are favorable. I'll give one area of caution patients who have G. I. Related cancers especially upper gi cancers. I'm thinking esophageal thinking stomach. I'm thinking pancreatic. They tend to have higher rates of bleeding in that directly available drug may not be quite as good an option for those patients. But for patients who don't have those G. I. Related cancers this is really a nice option and avoids the need for them to give injections. Well then you'll say okay I got one for you. How about anti phosphor lipid antibody syndrome? And I'll say okay I think here maybe you have me but probably not as broadly as you might think. This is actually one of a couple of studies that have shown that vitamin K. And that um direct oral anticoagulants in this case it was River Rock salmon do worse than standard therapy with vitamin K antagonist. This is from six hospitals in spain where patients were randomized. However, I will note that more than half of these patients had what we call triple positive anti foss Philip and antibody syndrome meaning they had three different antibodies that were all elevated. Now that is certainly something that we see but is by no means the most common presentation. Most of the time. We'll only see one or two antibody positive. There was also about a third of these patients who had arterial embolus events or thrombin tick events rather than the more common venus thrombin, thrombin tick events. So the way I look at sort of these different subgroups of patients is we can now use directoral anticoagulants in our full range of body mass, index and weight. We can use these in most patients who have cancer associated VT with the caution around Gi cancers and for anti fossil lipids syndrome. I would not use these drugs for those with triple positive or arterial thrombosis, chick, anti fossil put antibody syndrome. And I think we're still trying to sort out the data on the more common but lower risk, single or double positive studies. I would be cautious, but I wouldn't make it an absolute no. And I realized that's not necessarily in the package label. That's just my read of the data and the way I practice in that space. Okay, I want to move to uh the next question, which is how long should we treat patients? And if you've got a little bit of that snack in your belly and you're starting to zone out, this is the time to wake up because this is the one slide I want you all to think about and remember when you walk home from today, this is actually my favorite study to talk about. These were patients who had venus thrombosis embolism, all of whom received six months of therapy. They all received their anticoagulants. Warfarin for six months at that time, We then randomized them so that half of them continued on warfarin for another 18 months. A total of two years. The other half after a six months course of very good primary treatment course switched to placebo. And as you can see here, the placebo line in orange immediately starts rising as soon as they start on placebo while the warfarin arm in sort of that dark blue or that black stays very low at zero all the way through that treatment phase, which tells me that when patients continue on Warfarin, they don't have recurrent events As compared to when we stop Warfarin. They do have recurrent events but notice what happened at month 18 or total two years 24 months of treatment when we stopped warfarin. At that point, those patients started accumulating events. And what this tells me is not only is Warfarin better than placebo at preventing VT recurrence, but it does not matter how long you were on treatment. It's whether or not you're on treatment. So I see this all the time. People say I'm a little concerned about this person rather than three months. Let me give six or instead of six. Let me give 12. And my answer to them is you're not making any difference except for that three or six month period. The question is whether or not you want to treat that person long term or whether the risk of recurrence is sufficiently low that you think it's okay to stop longer, therapy won't protect them beyond the time at which you stop their antique wagon. And I think that's a really important message to take home. So how do we think about recurrence risk? What we think about what maybe was the factors that led to their initial clot? Was this something that was surgically provoked? A strong yet transient reversible risk factor? Their recurrence risk is quite low. Was there no identical factor? Something we call unprovoked or was it even worse associated with cancer? These patients are at much higher risk of recurrence. We can start to bucket people into different groups. I hear a lot of people talk about air travel and they say, oh well I just came back from a plane flight or this or that could that contribute. This is a really fascinating study where they looked at patients who arrived at Charles de Gaulle airport from all over the world over the course of almost a decade. And they found that the farther you traveled, The higher your risk of thrombosis was. But really, the inflection point was over 7500 km, which basically means you have to have an overseas trip. We're not talking about people traveling between Miami and Cleveland. We're talking about people flying from Tokyo to Cleveland. So if you're in a plane flight that's lasting more than eight hours. If you're in a car ride and you're literally not getting out of that car ride for 68, 10, 12 hours. Those are the people in whom I'm starting to get more concerned about otherwise, it's probably a pretty small risk factor. There's something else underlying going on that's contributing to that VT risk. Now we talked for a minute about the ability to do that secondary phase, that dropping of the dose. And this is the data that supports that. I want to make one point clear here, which is these were patients, all of whom had equipoise about whether they even needed to continue anti coagulation beyond the first six months. So whether you compare two picks even versus placebo or river rocks, even versus aspirin many of these patients, we weren't sure what to do. And in fact in the Einstein choice study, 60% had to provoke VT So even in patients in whom you can identify a risk factor, that risk factor isn't reversible. You may want to think about using longer term courses of anti coagulation. And really there's this spectrum of provoking factor from weak things like travel to really strong like major surgery, major trauma, things like that. And so it's not quite as binary as perhaps many of us have been taught or the ways we often think about this. So the guidelines tell us from the american college of chest physician that for transient risk factors, it's a three month course and with no real risk factors. Then we think about extended or indefinite anti coagulation. The ash guidelines, american society hematology really really echo that same approach. And so they do agree that that would be the way to differentiate these patients. So if we think about our patient this was a 62 year old woman. She had that plane flight, not a very long flight, she was low risk. So we treated her as an outpatient, used that starter pack if you can her B. M. I was 42. It's okay to use the starter pack. You know, she does have obesity which is a persistent risk factor. The plane flight was a pretty weak factor if anything. So I'm gonna think about a longer course of anti coagulation in her. Um and have that conversation with her at that 3-6 month mark. Now I was asked to touch briefly on covid. You know, covid is surging again. I just got a notice from my hospital. We have over 100 patients with covid in our hospital right now and we're thinking a lot about how do we prevent thrombosis complications. There's a couple of trials. I just want to make sure that you're aware of. This was the active for B study. This was a study looking at patients with Covid who were not hospitalized. So the ambulatory patients with covid really saying, hey, are they at risk for thrombosis. Anyone who's been on apart service knows that we see people who come in with a P. E. Who had covid in the last couple of months. Is there a way we could prevent that? Unfortunately this study was not able to identify a good preventive strategy. You can see here that whether they got aspirin or whether they got either a standard or reduced dose of a pixel band or even if they got placebo, there was really no difference in the cumulative incidence of thrombosis tick events. So we should not necessarily be treating patients with ambulatory covid with antiserum biotic agents. We don't have the data to support that yet. What about the person who is hospitalized and is now getting ready to go home? Are they at continued risk of thrombosis? And the answer is I'm not sure. A number of studies initially suggested that risk was probably pretty low. Those are the ones circled in green but we actually have some newer data suggest. Maybe that risk is a little bit higher. One example is circled here in red. We actually have a trial that was presented at the E. S. C. Meeting a couple of months ago. I've heard rumor. It may be coming out in press in the next week or so. So stay tuned. This was the Michelle trial. They randomized patients prior to hospital discharge to either get an extended course of river rocks oven for 35 days or placebo. But importantly these were all patients who are at high risk for thrombosis they use something called the improved score and they combine that with a. D. Dimmer level to try and be really selective. And they were able to show a pretty remarkable reduction in the rate of thrombin, attic endpoints venus arterial M. I stroke limb events and even cardiovascular death from 9.4% To about 3%. And they also reported no major bleeds in either arm. However as a randomized trial was pretty selective. I think we're gonna have to wait and see how well this applies to a more general practice-based population and what some of those real world outcomes look like. But it's certainly something to consider if you have a high risk patient in whom you're somewhat concerned. So this is my strategy for how I'm approaching thrombosis prophylaxis. In patients who have covid my outpatients. I am not recommending anything to them. I am just saying stay hydrated ambulance. Just don't get around anyone else. So do that in the confines of your bedroom for the floor patients. I'm mostly using standard dose prophylaxis. But if they have high risk features I'm considering treatment or therapeutic anti coagulation for the ICU patient. We're sticking to standard doses of prophylaxis and that's based largely on the multi platform trial. Same for patients with a R. D. S. Of course if you have a confirmed or suspected VT we need to treat that like we normally would And in the post hospital phase, I'm only going to think about extended prophylaxis if it's a very high risk patient Um this is likely to change as more studies come out but this is at least where I stand today, December 10, 2021 so you can take that for what it's worth. So I want to say thank you so much for having me. Thank you. Dr Gornick for hosting. This has really been an honor mm hmm. Why don't we take a few questions Dr huber. I don't know if welcome to Cleveland and thank you so much for the great presentation. You focus your presentation on low risk p patients from outpatient setting. And as you heard earlier from DR Shields, you know, we have a very intensive program and a lot of the higher intermediate risk patients are now being treated you know with various technologies if they're appropriate. So the question is that your criteria from the standpoint of the outpatient versus inpatient, Is it based on the acuity of the of the pE or the clot formation or is it based on human dynamics? Meaning that if you have addressed the human dynamics, would you be comfortable with sending those patients home sooner rather than waiting for two or three days in a hospital on heparin or so. Yeah, I think it's a great question And and the thing I always try and remind folks is that we pick up a pulmonary embolism by seeing the clot. But I risk stratify them based on the right ventricle and the lung. So it's about the human dynamics, right? If that heart rate is normal, the blood pressure is normal, the oxygenation is normal, that's very reassuring to me, even when somebody has a large clot volume or more central Claude. Now there's some data to suggest central clot is a bit of a risk factor. But on the whole it's the it's the vital signs that we look at. It's the trend in vital signs that I'm really interested in, to think about who gets advanced therapies, who gets observation and when somebody is ready to go home, Jeff, this is a little off topic, but you can you comment a little bit on deed. I'm er I see a lot of literature on age adjusting D. Dimmer and how are you currently using deed? I'm er yeah, thanks. And it's such a timely question. There was just a paper published looking at this, you know, I think the deed I'm er we now have a pretty robust set of evidence to say it should not be a fixed number for everyone. Many of us are used to the 0.5 or the 500 depending on your units. Um But really as we age we know that that d dimmer can go up. So at a minimum when I'm thinking about diagnosing DVT or pE I'm thinking about using an age adjusted D. Diamond which the base threshold is that 500 or 5000.5. But then it increases it's basically your age times 10 as it goes up. There have actually been some newer studies to try and come up with more complicated regimens using different risk scores like the years score and based on the number of risk factors. Do you have a deed I more of this versus an age adjusted D. Dimmer. And in general they tend to work because they're well thought out. The question of course is are they practical and can you operationalize them in an emergency department? I think if if you're individually seeing a patient you're ordering a deed. I'm er think about using that age adjusted D. Dimmer. The 65 year old could probably have a cut point of .65 or 650. You don't have to use the 500.5 threshold for them. And there's a number of studies that have supported that. Now. Other questions. Dr wong hi dr mars great talk thank you very much. One more patient population so E. S. R. D. On hemodialysis. Um Seeing lots of variation. Um Full dose of pixel band half those two picks a band. Um Not really any of the others but this is a patient population. You'd love to keep out of the hospital. And yet they're the ones you can't use any of this stuff or use it reliably and and so they're gonna and they have no I. D. Access, you're gonna end up on a Hepburn drip. You can't use an ox parents. So comments on on those folks. Yeah, so this is a really challenging situations. So I always make the distinction for your end stage renal disease patients on dialysis. You can use direct oral anticoagulants but it's important to differentiate the indication. So for venus thrombosis embolism, the package inserts would say use the standard dose of a pick Saban. It's contraindicated for patients with a creatinine clearance less than 15 for River Rock Saban. And the Janssen folks in the back will check me on that to make sure I didn't mix that up for a fib. The package inserts would say it's okay to use both of those drugs. Um and the way I usually approaches, I say, ok, I would use the standard doses of them. However, we know that in general with a fib we don't know if there's a ton of benefit from anti coagulation in those patients. And so this is actually a great opportunity from for some emerging drugs, some factor 11 A inhibitors which are going to be tested. This may be a really great opportunity for them to grab some market share. But today I would use a dough act, I would just make sure the patient is aware of the potential increase in bleeding risk. Certainly better than taking Lovenox shots which are also have issues in that space as well. Thanks so follow up question that's about effectiveness. Now the question is about reversal or holding for invasive procedures or for acute bleeding episodes. Yeah. So so so another great question, reversal of anticoagulants. So we do have targeted reversal agents for all of our directoral anticoagulants. Darius is a mob is for the big Atran and excellent alpha is for all of the factor 10 A inhibitors. Many centers mine including have limited when you can use and Excellent Alpha only to inter cranial hemorrhage because of the extremely high cost and so what we tend to find is we're using um P. CcS. So um Kay central would be the brand name for for a lot of those. Note that it's usually being used for acute bleeding. I would much rather you wait two days for your surgery if at all possible. So that drug can clear out and Dixon alpha is not approved for emergent surgery only for acute bleeding. And is it is it predictable how the drug clears out? Yes, it is very predictable how these drugs clear out of your system. Multiple studies, biggest one being the pause study showing that for almost everyone 48 hours is enough time for these to clear out of the system and not have clinically meaningful drug levels. Last question please introduce yourself. I'm sure one of the cardiology fellows here just tell question that I come across multiple times. If you have small sub segmental pE or small infra postprandial DVT. I have seen the practice where you do anti coagulate. Some people would say some people won't. And the guidelines were sort of now updated and suggesting towards not anticoagulants. What's what's your take on those patients? I feel like you all have just read the literature in the last week and you're asking the right questions. This is so great. So distal DVT meaning, you know, isolated distal DVT below the knee. You do have the option for serial imaging, imaging uh and then repeat imaging in a week to make sure it hasn't progressed. That is certainly a practice. Some patients would prefer to be on an anti coagulant. I use both. The pe question is a little more interesting. We used to say, hey, sub segmental pe is it even real? Is it doesn't matter. Maybe you don't need to anti coagulate it. We just had a big study come out from the group in Canada saying yes, it probably is a risk factor. Yes. When you anti coagulate them, they do better. So, I'm now thinking if I'm if I'm certain that it's a real pe I'm looking at it with the radiologist were convinced I'm going to treat that person for a minimum of three months. The leg. I'm gonna give an option to the patient, they can either come back for imaging or we can treat and I'm happy to go either way. All right, well dr Barnes is going to be joining us for our networking reception so you can ask him anything you ever want to know about anti coagulation. DR Barnes thank you very much for joining us.