Narrator - Dr. Abel 00:00 Lange, welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. This podcast Narrator - ? 00:11 is provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 00:27 And now on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk episode 77 I'm your co host, Dr. Kane. I'm Dr. Schuman, and I'm Dr. Patel, and the title of today's episode is PE not just a class in junior high top five clinical pearls about pulmonary embolism. So today we're talking about some clinical pearls related to PE, or pulmonary embolism, that every pharmacist should know. Speaker 1 00:49 And that's going to range from the diagnosis of PE to its different classification and the treatment. And we're going to focus a little bit more on not the anticoagulation so much, but the alteplase used, that's the clot buster. Dr. Sean Kane 01:01 So just to kind of start things off, I think before we get to those five clinical pearls, we first have to just set the stage for those that may be a little bit less familiar with pulmonary embolism or PE, sure. Speaker 2 01:11 So PE, pulmonary embolism is a blood clot in the pulmonary artery occludes blood flow to the lung, which is obviously a bad thing. So we know that less blood flow to conduct oxygen exchange in the alveoli leads to hypoxia. Right side of the heart has trouble pumping blood through the pulmonary circuit, so left side of the heart doesn't get much blood as well. So beyond the hypoxia, you've also got hypotension, Speaker 1 01:33 yeah, so you reduce your output basically, and that leads to lower blood volume, leading to the hypotension. Dr. Sean Kane 01:39 And it turns out that all of your cells in your body need blood in terms of pressure, and they also need oxygen that is carried by the blood so pulmonary embolism can actually be a fatal condition if you have too low of blood pressure or you have too low of oxygen content in your blood. Speaker 1 01:56 And in a majority of cases, you're going to find PE that is caused by a DVT, and that's your deep vein thrombosis that occurs in the peripheral arteries and your extremities that embolize it so happens to be in the leg, and then it kind of moves towards the right side of the heart and then lodges into a pulmonary artery. Dr. Sean Kane 02:14 So now we've got the one minute version of what is PE and where does it come from. Now let's go ahead and start with our five clinical pearls for every pharmacist regarding PE. The number one deals with the diagnosis of PE. And the thing to know here is that you can't really diagnose PE clinically, meaning you can't look at a patient say you have a PE. What you can do, though, is say, I think you have a PE, and then have one of two confirmatory diagnostic tests for that patient. And those tests, which is our clinical Pearl is to diagnose a PE, you have to have a CTA, which is a CT with contrast, or CT angiogram, which is the gold standard, or in select patients, you can do what's called a VQ scan, which may help assist in the diagnosis of PE. Speaker 1 02:57 So then, in order to progress through those tests, what kind of signs and symptoms are you looking for to say maybe there is suspicion for PE so Speaker 2 03:04 some of them, again, I break them down into respiratory and cardiovascular — these are very similar to, I know, when we do our clinical monitoring, these are the same things we're asking somebody. And one thing about is these are not specific, again, so we can get some overlap with MI, and therefore we have to be a little bit more discriminatory about figuring out what's going on, but respiratory symptoms, things like shortness of breath, fatigue with exertion, hypoxia, tachypnea, increased heart rate and increased respiratory rate. Cardiovascular, as I said, tachycardia, palpitations, chest pain as well. Dr. Sean Kane 03:33 So again, if you think about it, chest pain, tachycardia, hypoxia, there's a lot of conditions that can cause those problems, which, again, is why we can't diagnose a PE clinically is just on our differential diagnosis of a number of other conditions A patient may have. Speaker 1 03:50 And I've heard some acronyms about you know, you come up with the scale, or there is a score that we calculate for these patients to maybe put them up higher on the ladder of higher suspicions for PE. What are some of those scores? Dr. Sean Kane 04:04 So the main thing to know is something called wells criteria. They have wells criteria for PE and also wells criteria for DVT. But basically, you use the wells score for PE to help you decide whether the risk of this patient having a PE is a low risk, a moderate risk or a high risk. In terms of what is the probability that what you're observing in the patient is a PE versus something different. And basically what this will tell you is it risk stratifies the patient in terms of an objective way to quantify your clinical suspicion of PE in a patient. So what you do is, if you have a low probability of PE from your wells criteria, you basically have to say, well, do I really want to proceed with diagnostic testing or not? Because, as we'll talk about, there are harms associated with the diagnostic testing, specifically that CTA, so if they have a low probability, there's another screening tool called the PERC rule (PERC test) that you can do in a patient, which has very similar criteria to what Wells score has. Has this asks questions like, Does the patient have a DVT? Are they tachycardic? Do you personally have clinical suspicion that they have a PE have they had DVTs or PES in the past? How old are they? Basically, it's a combination of past medical history risk factors and then clinical presentation risk factors. It gives you a score. Now, Dr. Kane, Speaker 2 05:18 one of the things I'm familiar with at our facility a lot of times again, we're considering something like a D dimer test. So when does that come into play here? Dr. Sean Kane 05:25 If this PERC rule is negative, meaning the patient doesn't have any of the criteria on this PERC test, you're done. You had a low probability from your Wells criteria, the PERC rule says you're done with your diagnostic evaluation — they almost certainly do not have PE. If you're PERC-positive (which is pretty easy to be based on heart rate or age), then you do have to proceed with a lab test called a D-dimer. Now, D-dimer is really tricky because a lot of different things can make your D-dimer level in your blood higher. D-dimers are breakdown products from blood clots, but this could be breakdown from trauma that you had two weeks ago. It could be an MI that you're having where you have a clot from the MI, could be surgery that you had and your body's healing by forming clots in the area where you had surgery. So lots and lots of things can make your D-dimer level high, but if your D-dimer is low, you almost certainly don't have a PE — so if your D-dimer is positive, it doesn't really mean anything except you have to keep doing more diagnostic evaluation, but if your D-dimer is negative, then you can stop again, just like with the PERC negative, we could stop at that point. Speaker 1 06:29 So same goes for a PE that is of intermediate probability. We would go with D-dimer testing. If it's negative, then no PE. But if it's high, then we move on with the diagnostics or the imaging. And then with the high probability cases, we jump right to the diagnostic, like the CTA or the perfusion test. Dr. Sean Kane 06:49 They can tell you, like in the ICU setting, because we're so concerned about PE, we have a lot of patients that have a lot of risk factors for DVT and PE. Generally speaking, a provider doesn't actually go through the entire process of PERC rule and Wells criteria and D-dimers because PE is so common in the ICU setting — oftentimes we'll just go straight to imaging because their clinical suspicion is so high. Officially, you could potentially do Wells criteria and say yes, they're at high clinical suspicion. Don't mess around with D-dimer and just go straight to imaging. Speaker 2 07:21 And Dr. Kane, one of the concerns I've heard about is, is he said someone's going straight to the testing, is that these tests, they're there. First of all, they're not foolproof. And then also, is, there's a lot so some potential concerns with them. So what are some of the these maybe deal breakers that we have to worry about if you were just to test everybody? Dr. Sean Kane 07:36 Yeah, so I mean, the the main test that we're going to do is going to be a CTA, CT scan with angiography or CT with contrast. And basically, there's two problems here. One, we're using radiation to come up with an image. You know, a CT scan is basically a bunch of X rays that are kind of glued together in a computer program. So all that radiation that comes from the X ray is going to be exposed to the patient, and then the dye that we have to use, so that contrast is dye. It's IV contrast, and patients can have anaphylaxis from the dye. More commonly, we can see contrast induced nephropathy, or acute kidney injury caused by the contrast. Although this is the preferred modality, sometimes we won't pick it because we're worried about patient's kidney function or the radiation exposure in someone who's pregnant, Speaker 1 08:21 for example. So for those patients, what's the alternative? Dr. Sean Kane 08:24 So the alternative is what's called a v Q scan, which, if you think about it like it's a crazy acronym, because v Q stands for ventilation perfusion, but that actually comes from kind of physics terminology in terms of perfusion, with Q being a perfusion variable. So the v Q scan is basically where you inject a patient with a radioactive isotope. It has a pretty low amount of radiation, emits gamma rays, and then you basically map what their blood circulation looks like in their lung. And then the next step is that you have them inhale a similar radioactive isotope, and the map where their lung is supposed to be in terms of where air goes. And then you compare the two. So you're comparing Where does air go versus where does their blood flow go. And if you see areas where you get air going but no blood flow, there may be a blood clot that's preventing blood from getting to that portion of the lung. So that Speaker 2 09:15 sounds actually like a pretty reasonable thing. So So why isn't this one used more frequently? Dr. Sean Kane 09:19 So the problem is that very often you'll get a non diagnostic result, meaning that they can't fully rule out or rule in a PE so it's like an indeterminate result. And this could be anything from someone with pneumonia or heart failure, where they have fluid there that's preventing you from getting good imaging of the lung, to they move a little bit, or the timing of the result is just wrong, where you can't get a really good comparative picture between the two, so that's why the CTA is the preferred result. But again, the CTA carries the risk of radiation exposure and contrast induced nephropathy. Speaker 2 09:51 So at least it gives us some options. So again, if we have somebody that's at risk for contrast induced Aki, Dr. Sean Kane 09:57 exactly. Yep. Speaker 1 09:58 And so moving on from. The testing and diagnostics and presentation of clinical symptoms. Let's move on to maybe breaking down the classification of different PE. So the term I've heard quite a lot when I read the charts is patient had a massive PE. So if somebody is reading it off the chart, they think that it's just a giant amount of clot, or a large clot in the PE? Is that correct? Dr. Sean Kane 10:22 Actually, no. So I'm really not a fan of this nomenclature at all. So as you said, Dr. Patel, massive PE makes it sound like the clot itself is large. And oftentimes it is large when you have a massive PE. But it doesn't have to be. So really, the criteria for massive PE is that you have a low blood pressure caused by your PE. So the definition would be a systolic pressure less than 90. And the reason that this is a big deal is that patients who have massive PE, the risk of dying from that PE ranges from about 25 to 50% so this is a very life threatening condition where many people die from that massive PE. That is a very large mortality Exactly. So really, like the nomenclature of massive PE probably isn't the most descriptive name possible. Something like hemodynamically unstable PE doesn't sound as sexy, but it's more descriptive of what the actual criteria is to meet that definition of massive PE. Speaker 2 11:14 So Dr. Kane, though, what does so as we classify? What does that mean as far as treatment Dr. Sean Kane 11:18 options go? So because the mortality rate is so high 25 to 50% with massive PE, we're more willing to be aggressive in terms of our therapies for the patient. So for massive PE, unless they meet a fairly small list of contraindications, we're going to give them thrombolytics in terms of TPA or alteplase to basically break up that clot. So we can hopefully help the right side of the heart pump blood to the left side of the heart and help with that hypoxia. Speaker 1 11:43 So it just sounds like somebody who had a stroke and we give them multiples to break the clot. It's similar to that situation. Dr. Sean Kane 11:49 Yep, same drug. But as we'll talk about with another clinical Pearl, there are some critical things to know about the differences between using TPA for stroke versus TPA for PE. Alright. So before we get Speaker 2 11:59 to that, though, we've still got to kind of break down some of the different types of PE. So the next part of it is submassive or intermediate PE — that's one where the blood pressure is normal, versus systolic less than 90. But they've still got some biomarkers on the such as, like a right ventricular RV strain. Is that correct? Yep. Dr. Sean Kane 12:15 So an intermediate or submassive PE is where the PE is causing damage to the heart or causing some structural problem. So most commonly, this would be that your troponin goes up and again, when we talked about some of the clinical signs and symptoms, they're very similar to what we see in heart attacks as well in MI. So we'll see increased troponin in the submassive PE just like we do in heart attacks. But we'll also see things like elevations in BNP, which is something we see in heart failure patients. And if we do an echocardiogram on these patients, the right side of the heart is often very dilated, and the reason is that the heart is pushing so hard and it has so much pressure on the right side of the heart, and no matter how hard it tries, it's having difficulty getting blood to pump through that pulmonary circuit, because there's a big clog there, a big clot that's making it hard to pump that blood through. Speaker 2 13:02 So what does that mean, as far as using TPA compared? Is it? Is it still the same, where we probably want to use it, or what's going on? Dr. Sean Kane 13:09 So this is actually a very controversial area of PE medicine. The mortality risk in these patients is highly variable. So if you have more and more biomarkers, if you have more and more RV strain, you probably have a higher risk of mortality, but within this category, there's a wide range of mortality, which makes it hard to decide when to be more aggressive and care for these patients, because some will never die from this intermediate PE, and some have a fairly higher risk of dying from their PE, and I guess Speaker 1 13:36 it based on other comorbidities and what the patient's clinical situation Dr. Sean Kane 13:40 is exactly well, suffice it to say it's not as clear cut when you use thrombolytics in this intermediate PE category, sometimes you will, most of the time you probably won't. Speaker 1 13:50 And the last category is your low risk PE, where probably the blood pressure is very normal. There is no elevation or abnormalities in the biomarkers, and there is no right ventricular straining or enlargement seen. So again, with these type of PDs, the mortality is pretty low, and we don't use TPA for this patient, because that risk versus benefit ratio is kind of off with that, and what we do for these patients is just basically anticoagulate them, yep. Dr. Sean Kane 14:18 So our third clinical Pearl regarding PE deals with what we talked about earlier with Dr. Patel, that using lytics or TPA or alteplase for PE is dramatically different than the dosing, the criteria and things like that, than what we use for ischemic stroke. And usually when you think about TPA, you think about stroke and not PE. But when you're using TPA for these PE patients, it's really important to know what are the differences between the two. Speaker 1 14:43 So you're trying to say that I don't have to remember the 15 contraindications for using T PA for stroke when I'm using it for Dr. Sean Kane 14:50 PE, you don't, and just to name a few. So things like anticoagulation is going to be the biggest one to think about when you give TPA in a stroke patient, if they are. Actively anticoagulated. It is a no go. You cannot give TPA if you have a patient with, you know, an INR that is too high, or if they're on a doac, or things like that. Whereas with PE, as we'll talk about, sometimes we'll actually anticoagulate them while we're giving them the TPA, which would be like, absolutely insane if you were doing that to a stroke patient. Now what if you've got somebody Speaker 2 15:19 who's bleeding, though, I assume that still, you don't want to give it to somebody who's got an active bleed in their Dr. Sean Kane 15:24 brain, right, of course. So we're not totally throwing out that laundry list of contraindications, but the risk benefit ratio is dramatically different here. Other things to think about are our time frame. So with stroke, you have this three to four and a half hour window where you could potentially give TPA. With pulmonary embolism, sometimes we'll give it days into their PE, especially if they're progressing and getting worse. In addition to that, the dosing is different. So with stroke, we would give point nine milligrams per kilogram, up to a maximum of 90 milligrams, and 10% of that is given as a bolus. Whereas with PE, the dose is way simpler. You give the whole bottle, which is 100 milligrams over two hours. It's not weight based, you just give it. Speaker 1 16:01 So the calculation of the dosing and whatnot is so much easier with the PE rather than using it with the stroke patients Exactly. Dr. Sean Kane 16:10 And I think that you know, the critical point here is, dose is different. List of contraindications is different. And the reason for it being different primarily is that trade off of risk and benefit. When you give TPA in a stroke patient, you're doing it for neurologic outcomes, not for a mortality benefit. Whereas with massive PE, they could die from their massive PE, and we could potentially save their life by giving them TPA. So we're willing to accept a slightly different bleeding risk in the patient with pulmonary embolism. Speaker 2 16:38 And again, we think about certain really targeted organs like the brain, and the fact that we're generally not expecting there to be some sort of neurological insulator bleeding there, we have to worry about it right Dr. Sean Kane 16:49 off the bat, exactly, and we'll talk about it later in terms of that risk. But generally speaking, your risk of bleeding when you have a pulmonary embolism and you give TPA is a lot different than in a stroke patient population for a variety of reasons. Speaker 1 17:02 So diving a little bit deeper into that gray zone, we talked about the intermediate category of PE, and you mentioned that, you know, the use of TPA really depends on what patient is in front of you. So what is the evidence of TPA use in this particular type of PE category? Dr. Sean Kane 17:18 So again, this is very controversial, and we only have a handful of studies that have really fully investigated this at this point using the entire amount of data that we have. The expert opinion is essentially it's a case by case basis, so it probably helps some patients. It probably doesn't help other patients within this category, and the expert has to decide who is most likely to benefit on a case by case basis of the data that we do have, the PEITHO study is the best one. It's the largest one — if you want to look at a reference to the PEITHO study, it's available at HelixTalk.com for episode 77 and this is the best study we have to date. It did not change mortality and many of the other studies have not shown a mortality benefit within this category, but again, looking at all of the data, it probably has some benefit on certain morbidity end points that we're looking at. So this could be pulmonary hypertension incidents. It could be incidents of heart failure. They haven't done a lot in terms of overall quality of life and exercise tolerance, but the thought is that if you can prevent pulmonary hypertension, you probably can help quality of life to some extent. But again, these studies are fairly small, and of the studies that we do have, they're not looking at the endpoints that maybe we would want to see in a larger study. Speaker 1 18:31 So like I said earlier, the timeframe for administration of TPA, for PE patient is so large that if you had a patient in front of you, and you quite weren't sure you know whether they fall under massive versus intermediate and they were progressively getting worse. We still have time to consider giving them alteplase Exactly. Dr. Sean Kane 18:50 And I would say that at least in my experience, when we do give a lytic to someone who has an intermediate risk. PE the typical scenario is they look bad. Maybe they go to the ICU for respiratory distress. And if they start getting worse and worse, even if they don't officially meet the criteria for a low blood pressure, the respiratory status looks horrible. We might decide to give them a lytic because we feel like it will make them better. And again, at least in my experience, compared to stroke, when we do give the lytic to those intermediate risk PE patients, they look dramatically better within, you know, 30 to 60 minutes, and then definitely better after a couple hours. Whereas with the stroke patient, the benefit probably is a longer term benefit, as opposed to a very acute benefit. And of course, all of this discussion for this intermediate risk PE patient is hinged on the fact that we do have a bleeding risk associated with our TPA, and that's the other component here. It's not like the drug doesn't have adverse events. And that's the other decision point that commonly plays a role. Is, you know, did they have surgery two weeks ago? Is there some other reason that we're worried about their bleeding risk? And that's why that case by case basis is so important within this intermediate risk PE group. Speaker 2 19:58 And so speaking of bleeding risk, Dr. Kane. That kind of gets us to the final point, which is one that just completely blows my mind. Is the idea that in a massive pulmonary embolism, you can anticoagulate before, during and even after TPA administration. Again, that just really surprises me. Dr. Sean Kane 20:11 Yeah, and again, you would never, ever, ever do this. In an ischemic stroke patient, you can't give TPA if they're currently anticoagulated. You can't even give them aspirin 24 hours after they get TPA. So this is dramatically different than what we're thinking about for contraindications for ischemic stroke patients. But you're absolutely right, and a lot of the reason for that is the risk and benefit trade off. Notably, the actual bleeding risk is a lot different in PE patients versus those with an ischemic stroke, Speaker 1 20:41 and we're looking for, we're talking about massive bleed, bleed, like intracranial hemorrhage. So what's some of the evidence we have? And that looks at TPA and stroke patient, and looking at the ich rates and TPA use and PE patient, and looking at the ich rate. So if you look at the stroke patients in the use of TPA. It comes from the NINDS trial. The rate of intracranial hemorrhage was 6.4% but you look at the PE trials again, these are small trials, but more kind of just combined rate. The ICH rate was 2% — so this is where, as you mentioned, Dr. Kane, the risk-versus-benefit picture is completely different in PE patients. And a Dr. Sean Kane 21:20 lot of that probably deals with the fact that when you have an ischemic stroke, you're killing off some of that tissue in your brain. It's going to be more friable, more apt to bleed anyway. So when you give a lytic to those patients, of course, you're going to see a higher risk of bleeding in the brain, because now you have this friable tissue that has been damaged by your stroke. In pulmonary embolism patients, generally, we don't see bleeding in the lung caused by giving alteplase, and if they don't have this insult to their brain, we really shouldn't see super high risks of getting intracranial hemorrhage when we're giving it for a pulmonary embolism. And the Speaker 2 21:52 other important thing to note, then is that TPA has a mortality benefit in a massive pulmonary embolism, compared to the data we have with stroke, and that with stroke, really, we're looking at neurologic outcomes improvement instead, and that's about the main thing we're getting out of it. Dr. Sean Kane 22:06 And the other component here, in terms of this anticoagulation with PE, is that commonly, these patients are already anticoagulated — so maybe they had a DVT that got started on an anticoagulant last night, and now today that DVT embolized into a PE. So oftentimes, because of who these patients are and their risk factors, it's not uncommon that they'll be anticoagulated, or maybe you started a heparin drip for their DVT and it embolized into a PE, and now you have to do something to treat this patient who's now gotten worse. Speaker 1 22:36 So is there a recommendation as to when the anticoagulation should be started along with the TPA, Speaker 2 22:43 yeah, for somebody. Again, I think in the outpatient setting, these are always the things I want to know is, when do you start? When do you start? When you resume these things? Dr. Sean Kane 22:49 So there's really no clear answer in terms of that question. A lot of it, again, is going to be case by case basis. This is actually a very common question I get in the ICU setting, is, when do I start or stop or hold my anticoagulant when I give TPA for PE so of the data that we do have, especially if a patient is a lower bleeding risk, but they're more severe, you're going to actually give the TPA while your anticoagulant is on board. So let's say they're on a heparin drip. You'll continue the heparin drip and give them TPA at the same time for someone who is either a little bit less severe, where maybe they haven't had that cardiac arrest caused by their PE or maybe they are looking pretty bad but still mentating appropriately and things like that, you probably would be holding your anticoagulant if you can. So Heparin, for example, giving the TPA and then resuming that anticoagulant at some point in the future, if they're not currently anticoagulated, the same principle holds true. So if they're not anticoagulated, you give the TPA, you can either start your anticoagulation as soon as the TPA is running or done, or you can wait a couple hours after that, if you think that their bleeding risk is higher or they're not as severe. Speaker 2 23:54 And I'm assuming we can get away with this because of the half life of TPA. So it seems Dr. Sean Kane 23:58 Is it pretty short. So the half-life blows my mind — it's five minutes, wow. And within about an hour, it's basically completely gone out of the blood, which is interesting in stroke patients, not only because we didn't show benefit within 24 hours in the NINDS trial, but it was three months that we saw that neurologic recovery, but also bleeding risk in that stroke patient population. It isn't always within that first 24 hours. It usually is, but not always. So we see hemorrhagic conversions days later that may or may not be due to that TPA. But the context here: it's important to note that the TPA half-life is dramatically short, which should give you more comfort to be able to start your anticoagulant basically within an hour or two of giving your TPA. In addition to that, if you're incredibly worried. You can check an APTT value, just like we would with a heparin drip. This will be elevated after you give your TPA, and it will normalize after that TPA is gone. You don't have to do that. Some experts recommend doing this, which is fine, but again, it's probably a case by case basis in terms of if you're really worried about bleeding, maybe you can check that. PTT a couple hours after. After your TPA is given. If you're not that worried, just start your anticoagulant, and don't worry about the PTT Speaker 1 25:05 and the type of anticoagulation that is done in most cases, most acute cases, it's going to be your on and off switch, AKA your heparin drip. Good thing about using the heparin drip is that it's quickly reversible and it has a short duration of action. So again, the half life is much shorter than using some of the other injectable anticoagulant. But then once the patient becomes a little bit more stable, we can convert them to other agents for DVT/PE. So again, commonly used agents — especially low-molecular-weight heparin like dalteparin or enoxaparin — and then usually an oral anticoagulant, either a DOAC or warfarin, is started. Speaker 2 25:44 So that was my gonna be. My question again, is, so what's the role, for example, of the doac these novel agents, are we? What's the data for using them? Of the Dr. Sean Kane 25:51 doacs that we have FDA approved indications for, they were studied versus Warfarin with a bridge from low molecular weight heparin. So as far as the chest guidelines are concerned. We covered this back in episode 50, when we talked about the shocking recommendations from chest 2016 and essentially, the chest guidelines do prefer a doac over other therapies like warfarin, for example. But as we talked about in the episode I personally didn't fully agree with that recommendation in terms of efficacy, the doacs are equally effective versus warfarin, and of course, you're going to be bridging Warfarin with a low molecular weight heparin, until the INR is therapeutic, but the bleeding risks were a little bit different based on which doac you look at, which trial you look at, so it's a little bit of a mixed bag, but patient preference is probably going to be the main driver here in insurance coverage and things like that, because these patients are going to be on an anticoagulant for At least three months. Clinical Practice usually is going to is going to be longer than that. And there's a variety of other factors that play a role in basically how long you would anticoagulate Those patients for Speaker 1 26:49 lot of the time. It also depends on the formulary that the hospital starts the patient on this anticoagulant. So if they only have Xarelto on the inpatient formulary, then that's what they would start, and then the patient can be converted on the outpatient basis if they need to switch to one of the other agents. Dr. Sean Kane 27:08 So regardless of what you pick, a very common scenario, I'm sure on the outpatient side is, when can I stop my anticoagulant after my PE for you two and your experiences, because I don't see those patients in the ICU, hopefully they've left, gone home, and they don't come back. What is a typical scenario in terms of, what is the recommendation? What do you see in your personal practice in terms of how long they're on these doacs for? Speaker 1 27:27 So I try to follow the 2016 CHEST guideline recommendations — guidelines say, you know, three months of minimum anticoagulation is recommended, and the rest is up to the physician's clinical decision-making, looking at the patient's other risk, their mobility, their future risk of getting PE, and things like that. So I've I follow that, but I've also seen sometimes referral to specialists such as, you know, hematologists. They would prefer doing more hypercoagulability testing to find out if the patient has any genetic disposition for why they got the PE. And then, based on that, they maybe even do a repeat CT scan, for example, to say the PE is gone, we can stop the therapy now. Speaker 2 28:08 Yeah, again, I agree. At our facility, it's very common that, again, I work with primary care to manage and then at some point, you say, Let's console either cardiology or vascular and get get their assessment. Again, they may do a workup for some of the abnormalities, or, again, as do imaging. As you Dr. Sean Kane 28:23 said, great. So it sounds like it's probably a patient level decision. Unless bleeding occurs, you're gonna have a minimum of three months, but it may be longer or even indefinite, based on patient specific factors. So to kind of summarize some of the key concepts from today's talk, number one concept was the thought that you can't diagnose PE just based on clinical exam alone. You're going to need either a CT scan with contrast or CTA or a VQ scan, depending on a variety of patient specific factors. In terms of why you're doing one or the other in the process of getting there, you may do something like Wells criteria, the PERC rule, or even D-dimer to kind of assess the need to get that imaging in the first place, but the imaging is the final destination in terms of confirming that PE. And then Speaker 2 29:07 the next thing is, it's important to kind of classify a PE to get a better idea about some of the treatment options. So pulmonary embolisms can be seen as massive, which is dependent upon the blood pressure, systolic, less than 90, intermediate, where the blood pressure is normal, but there's biomarkers indicating some strain or damage, and then low risk, where they're stable, blood pressure is normal, there's no strain or no positive biomarkers. And then massive PE does have a significant mortality rate approaching 25 to 50% which is much different than the Speaker 1 29:35 other types. One other therapeutic agent we use for massive PE is alteplase. Remember, this is also the agent we use for ischemic stroke, but the dosing and the contraindication between the two different users is vastly different. Most notably, we use a fixed dose, which is 100 milligrams, regardless of the patient's weight, and it could be given even if the patient is completely anticoagulated. It could be given days into a diagnostic. Process of PE and then Dr. Sean Kane 30:01 in terms of that intermediate PE category, this is that area of clinical controversy in terms of should we give alteplase or TPA or not? Of the data that we do have, it probably does not decrease mortality in this patient population, but it may improve outcomes that may relate to quality of life, like pulmonary hypertension or exercise tolerance. But again, it does have that benefit at the risk of increasing the risk of bleeding, both minor bleeding and major bleeding in these intermediate PE patients. Speaker 2 30:27 And then lastly, something that I learned from doing this podcast is that anticoagulant can actually be given before, during and after alteplase administration. Again, obviously, in the absence of a bleed of active bleed, heparin is usually a preferred anticoagulant in the setting because of that reversibility that could get it in and get it out pretty quickly from the half life. So if major bleeding does occur again, pull it off and you can see some resolution quickly. Dr. Sean Kane 30:50 So that concludes today's episode. If you want to see our references at HelixTalk.com, we'll have a reference to both the PEITHO trial for that intermediate-risk PE patient population and also the CHEST guidelines in terms of what they recommend for more chronic therapy of PE after they get out of the SU and after their thrombolytic therapy. We're on Twitter at HelixTalk. We love the five star reviews, and iTunes keep those coming with that. I'm Dr. Kane, Speaker 1 31:14 I'm Dr. Schuman, and I'm Dr. Patel, and as always, study hard. Narrator - Dr. Abel 31:18 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store. Search for HelixTalk and place your review there Narrator - ? 31:29 to suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.