It is my great pleasure to introduce not only my colleague, but good friend, Dr. Vivek Kahl. He's going to speak to us today about the management of antithrombotic agents for patients undergoing GI endoscopy. I have been asked to speak on this topic, which I believe is also not only significant, but also has significant implications clinically and medical legally for the patient. So management of antithrombotic agents in patients undergoing GI endoscopy, no relevant disclosures in this realm for me. And just before I get into the next half an hour of this lecture, I think the one overarching take-home message or paradigm shift that the group can take away from this discussion is that in years past, in the textbooks, in the way people were taught and trained in GI endoscopy and gastroenterology, the pendulum was in the space where the GI bleeding and endoscopy took the top billing and the top precedence. The pendulum has shifted now, and people have realized that saving the myocardium and saving patients from a stroke is infinitely more important, makes a lot of sense. And therefore, the paradigm has shifted in allowing the anticoagulants to be not removed from the scene or brought back onto the scene very quickly. So there's a huge shift in that thinking, and that's where the field is going. So, the heart and the brain take precedence over the GI tract, and it pains me to say that, but that is the state of the science right now. Okay, the objectives of this talk are to review the bleeding risk associated with different endoscopic procedures, to also risk stratify thrombotic conditions that come into our practice in terms of what condition which patient has, review of some of the newer anticoagulant antiplatelet agents that are out there that we are all dealing with and will continue to deal with in future practice, and then current concepts and basic best principles on available data. So as I mentioned, the entire game plan here is to balance the risk and benefit of inducing or managing GI bleeding around endoscopic procedures versus the thromboembolic risk. And as I clearly stated the case, it's very difficult to get, it's impossible to get dead myocardium back. But almost in all situations in 2021 going forward, most GI bleeding can be controlled either endoscopically or through interventional radiology procedures, and in extremely rare cases with surgery. The important issues to consider in this realm are listed on this slide, and this is a complex topic. This will be a good slide deck to review on your own time as well, because it is so dense with information. But over here, we look at the nature of the procedure. Is it elective or urgent? That's a huge initial tenet to start your thinking process. Are we dealing with an elective procedure? We have time to review and manage things, or is this an urgent emergent procedure where we have a little bit of a different approach? Is the bleeding risk high or low? And that has been somewhat well-defined in the guidelines, both European as well as American, and I'll look at them next. The nature of the cardiovascular or cardio-neurovascular risk is important. Is the patient coming in with uncomplicated AFib, or is the CHAD score very high? Are there documented previous embolic events? What's the nature of the vascular anatomy there? What is the nature of the antithrombotic? Not all of them are equal. Is it a measurable effect like warfarin, or is it unmeasurable for the most part, like with the novel oral anticoagulants? Can we stop the anticoagulation in some way? Are there antidotes? And if the bleeding occurs in a particular viscous or organ or location, can I control it endoscopically, or can I not control it? Is it beyond my reach, right? So we'll discuss that a little bit. And then finally, last but not the least, is the communication aspect of it. When I'm dealing with a patient, it's not a silo situation. I'm one of several team members when you're dealing with a cardiac or cardio-neurovascular type of patient. There's a cardiologist involved, there's a primary care physician, a neurologist perhaps, an interventional cardiologist sometimes, and perhaps other people. So we just need to have a team in place where there is communication and documentation of an agreed-upon plan so that it's, first of all, safe for the patient, and number two, it protects you from liability. Risk factors for GI bleeding are listed here. They've been well-defined, and our colleagues around the world over the years have helped us understand that. Please make a note of these. These are older age, cigarette smoking, male gender, prior history of GI bleed, and renal insufficiency. So these are really very top-ticket items when patients come with these red flags. You need to pay attention. Obviously, the risk of taking NSAIDs and so forth goes without saying, but from a clinical perspective, this is what's important. Endoscopic procedures have been well-defined in recent guidance as having high risk for bleeding or low risk for bleeding. So on your slide, the left column is high risk for bleeding, which is intuitive, USFNA, PEG placement, resections, cyst gastrostomies, and so forth. On the right side are relatively low-risk procedures, such as diagnostic endoscopy, including biopsies, colonoscopy, ERCP with simply stent replacement, although there are caveats, but for the most part, that should be okay, push endoscopy, EUS without FNA, and most recently, Barrett sublation, which is also considered relatively low risk. So a very clear delineation, capsule endoscopy, low risk, very clear delineation between high risk and low risk procedures, which kind of sets the stage for the initial conversation. And it's important for both sides. So we should not be doing high risk procedures for bleeding with anticoagulants on board. And by the same token, we should not be withholding antiplatelet or anticoagulation therapy and presenting the patient to higher risk if we are doing diagnostic procedures. So it works both ways. And bleeding risk with common procedures is listed here with the various agents. Diagnostic endoscopy on warfarin is low risk and so forth. I won't belabor the slide, but you get the point. And this is something that will be available on the enduring material. And it's the same repeating message that a low risk for bleeding procedure can be performed while on antiplatelet or anticoagulation therapy, and the high risk procedure cannot and should not be. The other important message on that slide is that aspirin is low for all procedures. And I cannot overemphasize that. You know, in my unit, I run around a lot of the time saying that aspirin in our context is really not a blood thinner. Okay, aspirin is a cardioprotective agent in the right context. And it should really almost never be stopped. And that is in the guidelines as well. Now risk in the peri-endoscopic period is important. And it's depicted here on this slide. These are the conditions specifically which present a low versus high risk. So if you have an uncomplicated atrial fibrillation, never had a stroke, CHAD score is low, DVT is low, and so forth, they are all relatively lower thromboembolic risk entities. On the right side here, you have a high thromboembolic risk entities, which is mechanical valves in the mitral position, complicated AFib, history of recurrent DVT and pulmonary embolism, just had a patient with that all week last week with a gastric tumor that was sent in for a section and we have to manage them as an inpatient on IV heparin. Stroke, hypercoagulable states are very, very important to know and be aware of. So these are the really high risk patients that need to be managed very diligently. Risk stratification for discontinuation of antiplatelet therapy is mentioned here. Again, this goes to high risk versus low risk. Drug eluting stents in the first 12 months, bare metal stents, you know, within the one month of placement, very, very high risk patients that, you know, you got to have a very good reason to stop blood thinners in these patients. And most of these patients will undergo endoscopy for urgent and emergent indications and will not have that done if there's not a good reason. And again, some reiteration of the high risk situations versus low risk, which we covered a little bit. I want to point out that there is a small percentage of patients, especially in referral practices that have these anti-hypercoagulable syndromes. And whether it's genetic or systemically driven, keep an eye out towards that and do the appropriate investigations or refer them to hematology for that evaluation. So antithrombotic agents are listed here. It's kind of a broad term. You have anticoagulants, antiplatelet agents, and then there are mechanisms of action by inhibition of factor X and thrombin directly. This is where the novel oral anticoagulants come in. And so it's important to understand which agent is being used, where in the coagulation cascade that agent actually, you know, inhibits the cascade and what the mechanism of action is. And of course, on the antiplatelet side, the majority of the agents will be directly affecting platelet function through one mechanism or another. And then there is, of course, the special group of thienoperidines, which we're all familiar with, with clopidogrel or Plavix being the main agent there. So a knowledge of the variety of agents that are in the marketplace and will be on the medication list, how they affect and where they interfere with the cascade is important. Now shifting to the management guidelines, as I said in the very beginning, elective versus urgent. These are the two, probably the most important initial stratification and really dictates how we're going to approach this problem. So the general approach to a patient who is anticoagulated, we use the term broadly, a patient referred for endoscopy. It behooves us to actually see that patient in a consultation and we went over what an initial consultation should look like. And these are the patients that we have a unit driven policy that someone will see them, you know, at some point before the endoscopy procedure. And we personally will assess the cardiovascular risk and if need be, get on the phone with the cardiologist or the neurologist. When we discuss interventions such as FNA and endodyssection or other types of ERCP and stuff, we will talk to them that there will be an element of management of these blood thinners involved and which will present a finite risk for events around the procedure, cardiovascular events that we cannot completely remove, but we'll do our best to manage that. The other thing that becomes important is logistics, which is where will the procedure be performed? And, you know, different practices have different thresholds and different policies in place, but for the most part, the typical advanced interventional endoscopy procedure, which requires FNA, drainage, resection and so forth, and ERCPs are performed in a hospital outpatient department type of setting, which is appropriate with appropriate backup. And then, as I mentioned early on as well, is the initiation of the communication with the prescriber is really important. We have a nursing team that helps initiate that. And in contentious issues, the physicians or providers will need to get online. And this is another area where the APP collaboration is really key, is because if the endoscopist is in the procedure and the messages are coming in, you know, your PA and NPs can take a pole position in helping this discussion move forward. So the policies that need to be in place around procedural, very procedural management of anticoagulation is, you know, what the request is, you know, who is asking it to be held or restarted, who is informing the patient. If there is a disagreement on the timing, how will we get resolved, you know, and then the risk benefit, shared decision making with the patient and making sure that there is an appropriate indication for the procedure and then documenting all of that. If you do all of those things, then I think you certainly mitigate a fair amount of the risk on both sides. Now, a general approach to patients that need elective endoscopy or antithrombotics. One of the principles I've tried to follow is that if the elective issue, let's say, to make it simple, screening colonoscopy, if the patient is going to be on blood thinners for a finite amount of time, let's say three months or six months, then I would defer the elective procedure up to that time. Just don't lose track of the patient. The patient does need to come back when they're off of it. That's probably the simplest approach. Now, you know, shared decision making, you already referred to, you know, when you weigh the risk and benefit, if the procedure is semi-elective, then you can have a discussion around the timing and obviously triage the timing of the procedure to when it really needs to be done. I want to emphasize, I always do, that guidelines are there. Guidelines are not mandates and guidelines can never, not almost never, but never approximate every clinical scenario. So use the guidelines as a well thought out summary of data and combination of expert opinion. But your individual patient's customized situation is only for you to handle using the guidelines as a best resource. And whenever you deviate from the guidelines, you have to have good justification for that. So for example, a very common example comes up is Plavix or clopidroglut should be really held for seven days, but at five days, the majority of the antiplatelet effect is over. So if you say, well, we'll hold it for four days or five days, you say 80, 90% of the effect is gone. We should be okay doing this polypectomy, especially if we are putting endoclips there. So something like that's just a spur of the moment example that you can use to document. Again, emphasizing that aspirin really should not be stopped for any elective or urgent procedures. In fact, when patients come in on dual or multiple anti-thrombotic therapy, such as our LVAD patients, for example, the one thing we always continue and this data is shown that it's protective is the aspirin. If you stop everything, then they're at much higher risk for trouble. Again, the various thiopyridines, which is clopidrogl is the main example of that, their mechanism of action and the duration of effect, as I just referred to as listed here. So if somebody is asking you to hold it for a shorter period of time, as long as the procedure risk is perceived to be acceptable and you document that, and that's fine, but these are the official IFU-based informations. So here's an example of a patient who's at low risk for thromboembolism and the procedure risk is low. There is no adjustment needed, but if the procedure risk is high, five is the absolute minimum, seven is ideal. The patient is high risk for thromboembolism and the procedure risk is low. No adjustment is needed because the risk of bleeding is low, but if the procedure risk is high and the patient risk is high, then you need to have a little bit more investment of time, energy, and discussion and follow the guidelines with the recommendation is. Warfarin is probably the oldest anticoagulant that is out there. It's a vitamin, it interferes with vitamin K clotting, base clotting, and these are the factors that are affected, 2, 7, 9, and 10. Again, for most patients, about a five-day hold is adequate. Our policy is not to recheck PTINR, but I am aware that some units actually insist on that, and some service lines like IR may insist on that as well. If you do use vitamin K for correction, be aware that it takes a long time for when you restart the coumadin or warfarin for that INR to get therapeutic again, so use in small amounts, one or two milligrams, maybe five milligrams, and then escalate it if needed. There is a finite risk of thromboembolic events after temporary warfarin cessation. That's again part of the risk-benefit discussion, and again, higher risk patients should be bridged with low molecular weight heparin or another plan, depending on the guidance. So again, the same thing for low-risk procedure, I would continue the warfarin. For high-risk, you know, the patient will have to hold it, but high-risk procedure, high thromboembolic risk, you know, again, that's a problem, and this needs to be bridged, or the patient needs to be brought into the hospital, and you know, for example, mechanical heart valves and hypercoagulable states, especially those patients who have already documented that they've had recurrent DVTs, recurrent pulmonary emboli, and will most likely stroke out or have a heart attack or have a thrombus if you do not bridge them or manage them continuously. So this is an important tenet to keep in mind, but most diagnostic procedures with low-risk procedures and low risk of thromboembolic events can be performed without any interruption. The novel or direct-acting oral anticoagulants are listed on this slide. They directly affect the factors without affecting vitamin K or any other intermediaries. They're attractive recently in the last five to seven years because they have a fast onset of action and a fast offset, which makes pulling off and putting back on much more easier for everybody in the team. The minimum hold is 24 hours. It could be 48 hours or longer depending on renal function because they are renally cleared, but the caveat of checking with the prescriber and having that conversation still applies, and definitely have a plan for resumption in place. So this is the warfarin versus novel oral anticoagulant graphics here. This is the pharmacokinetics. In blue is the novel agents. They become therapeutic very quickly. This is hours over here, and this is percentage anticoagulation here, and you can see how long Coumadin takes to get up and how long Coumadin takes to come down, but with the novel agents, it's quick on and quick on out. So they have become the drug of choice for a vast array of conditions for cardiologists and neurologists at this time, and we like it too because really, if you're doing a colonoscopy with EMR on a patient with a normal renal function, if you go by the book, 24 hours of cessation, it should be good enough, which was not the case with Coumadin. However, the discussion changes if you have a delayed renal clearance. So if you have somebody who has got a GFR of less than 30, then you can go up to four days of holding, and this is an important thing to keep in mind as you do these consults and evaluate these patients, which is also the reason to see these patients or at least have a touch point with them prior to bringing them on the table. So I've already reviewed the risks here. Now, the important question that comes up is cessation and reinitiation of anticoagulation. This is a hard topic. There is relatively small guidance here from the literature, but again, the main sentiment here is to say, well, you know what procedure you did, and you have a certain amount of experience with that procedure and the bleeding risk after the procedure. You know the patient's cardiovascular risk, right? So at some point, this is a clinical judgment issue where you make recommendations, but just realize that compared to the past, when we were solely thinking from the point of view of the endoscopist or the GI team perspective, now we have to think from the point, well, what is the patient's cardiac risk and kind of balance out the recommendation. So the short version here is that resume it at the earliest onset that you feel is safe. And so it's becoming earlier and earlier and earlier. And I can tell you, at least in my practice, almost regardless of what intervention I do, ranging from a complex EMR all the way to a complex ERCP and everything in between, the vast majority of patients, I would say three standard deviations, have resumed their anticoagulation within 72 hours. It's even shorter than what's listed on this slide. So just if that doesn't send the right message, you know, I think that's where the take-home message is that we really, really want to narrow the window of the holding period, because I am reasonably confident that even if, despite my prophylactic endoclipse and whatever best techniques we use, even if they re-bleed or have delayed bleeding, we are confident that we should be able to control that. But I'm not confident that if that person has an ACS, that I will be able to retrieve their myocardium. So what to do if a patient is too high risk to stop antithrombotics? And that happened to me last week when we had a cardiac lesion in the stomach, sent for a section, and a patient with cirrhosis, Hodgkin's disease, and a host of other conditions, and a recent pulmonary embolism three weeks ago. So shared decision-making is important, a constant weighing of the risks and benefits. After a lot of discussion, you know, you may need to just bring the patient in and set the stage for further evaluation. And this patient ended up getting a TIPS procedure because his cardiac lesion was right on a varix in the distal esophagus, so it would have been foolish to do an EMR there. So these are really complex patients. This is not your typical scenario, but in referral centers, this can be a fairly regular scenario, and I wanted to highlight that. So again, patient and procedure risk assessment is critical. I talked a little bit about that. I think here in this side of the slide, you have colon polypectomy, USFNA, endoscopic ablation, stenting, and stent exchange. This is something you can get away with without necessarily stopping the anticoagulation, but interventional procedures, again, are reiterating the fact, especially things like liver biopsy and dilation and such, where if bleeding does occur, it's very difficult to control, as you're well off, you know, following the guidelines. In a patient with urgent procedures and GI bleeding, this is not an uncommon event, and, you know, a lot of our fellows and those who have inpatient APPs will deal with this scenario. Obviously, if a patient is bleeding, it makes sense to first control the coagulopathy, whichever way you want to do it, whether it's FFP, or if the bleeding is catastrophic, you may want to use higher dose vitamin K, time is of the essence, and go with that. Antiplatelet agents, of course, need to be stopped if the patient is bleeding. For severe bleeding, you may have to invoke platelet transfusions and DDAVP, because, and many institutions have policies on that, that are very strict, and sometimes it's a little bit hard to get these approvals, but if you make the case, it will be approved. Because any endoscopic therapy that you do is less likely to be durable if the patient still has a rip-roaring coagulopathy. Management of direct acting agents, such as I mentioned earlier, is typically in the GI bleed, they're managed as an inpatient, standard resuscitation protocols still follow, the agent should be held, an urgent endoscopic evaluation with an aim to provide really very robust and complete hemostasis, and dual or triple modality hemostasis, for example, with burning with cautery, endoclipping, and sometimes nowadays we even throw some hemospray on it, and some people do, because these patients will be going back on anticoagulation. Now, the good news is that some of these agents will have commercially available reversal agents that are available, they're not cheap, and they really should be used only for life-threatening conditions where nothing is working. Restarting antithrombotic agents, I already mentioned that, the resumption of aspirin and PPI has a lower rate of recurrence compared to not doing that. In fact, this particular study looked at continuation of low-dose aspirin after endoscopic hemostasis, which results in a lower all-cause mortality, 12% versus 1%, and a higher re-bleed rate, which is acceptable. So, people die if you stop their aspirin, but they may re-bleed, but they'll still live, and that's the message. I'll skip that one. Now, antidotes are important. I just wanted to highlight this because this is relatively new information, not necessarily for aspirin or warfarin, we know about these, as well as heparin, but for dabigatran and for pixaban, we have new agents on the market that are available. I'll emphasize again, these are not cheap, and they need to be used very, very selectively and judiciously for the occasional case, but that option is available. Now, this is my favorite slide. Difficult scenarios. This is a difficult topic in clinical practice, but this gets particularly difficult when you have to deal with these situations. A Jehovah's Witness patient, and somehow, in my practice, I ended up finding all these patients, and on our consent form, we have a thing for blood transfusion, and the one utility of that is that when you ask that question, every so often, a patient will say, I cannot accept blood, and that's a very important factoid that you need to know going into an interventional case. There needs to be a different plan for this patient, and it needs to be documented. The recalcitrant cardiologist who has put a stent 19 years ago and still wants the antiplatelet agent on, that can be a tough conversation. There are a few of them out there. The cardiologist cannot be found is not an uncommon scenario. I've chased a few in my life. LVAD patients, we have a cardiac transplant program here, and a huge LVAD community, probably one of the largest LVAD programs in the country, and they bring their own set of multiple anticoagulation, antiplatelet agents on board. Fortunately, this is a team-based approach, so we are able to navigate that on a case-by-case basis. The patient with the acute MI is an interesting one because if the patient with acute MI is bleeding out, that's neither good for his GI tract, nor is it good for his heart, but the patient with acute MI who has a new coronary stent is probably the most stable cardiac patient you will ever scope. So, keep in mind, the patient with acute MI is not an immediate turnoff. It is something you need to look at, and if they are bleeding, you should be able to do them with appropriate discretion. So, which risks are we willing to take? Are we going to continue the blood thinners? Are we going to stop everything? I think I've made the case that we are leaning now more towards continuing and resuming, continuing late and resuming as quickly, because we are confident that we can control the bleeding. The bleeding rates are not that high with this paradigm, but we cannot save the heart once it is dead. So, we can almost always stop GI bleeding, but ACS and CVAs are difficult to revert. So, some new web-based tools just to highlight. These are out there. Everything is web-based nowadays. So, this is a recent study published in GIE under the auspices of the ASGE, and this is tools that you can put in the data, and then it will tell you the degree of correlation, you know, in terms of what you're doing, what the guidance is, and where the gap is, and then you can potentially learn from it as well and apply that to your patients. There's another guide here that does pretty much the same thing. This is a smartphone app from Hopkins, and again, this is a learning process, but mostly there is concurrence. Most experienced practitioners will be doing what these guidelines are recommending, but occasionally, there's a question, and you can refer to that. So, general anticoagulation hold guidelines for elective procedures. For diagnostic EGDs, do not stop any blood thinners. For endoscopy with dilation, check with the provider performing the procedure as well as the indication for the blood thinner and have a conversation. PEG tube procedures definitely hold because you're transgressing an area that you don't have control for, which is the abdominal wall. For endoscopy, without too much intervention, you probably can continue. Double balloon endoscopy is typically done for some intervention, either it's ERCP or it's a resection of jejunal polyps, so you're probably better off holding. And then colonoscopy, again, is a big box, and we need to check with the provider. And, you know, many years ago, we showed that polypectomy was okay to do. Recent data has, again, suggested that. But most units will hold blood thinners for colonoscopy because polypectomy is envisioned as well. So, it's a unit policy and then a discussion from there. Practice falls. Aspirin can be continued for almost all, I would say all cases. Low bleeding risk plus high thromboembolic risk. You need to continue antithrombotic agents. High bleeding risk and low thromboembolic risk hold the antithrombotic agent. High bleeding risk and high thromboembolic risk, which is the most difficult category, you have to hold the antithrombotic agent, and you have to bridge, and sometimes you have to bring the patient into the hospital for IV heparin. Restart the medications as soon as possible post-procedure. I shared with you my experience, 24 to 72 hours max, sometimes same day. And patient-centered multidisciplinary approach, where all these folks are involved in the discussion and documented, is almost always the best strategy. Thank you for your attention. And I think there will be some polling questions. So, the first polling question is, all should be considered when stratifying risk of interrupting antithrombotic agents prior to an endoscopic procedure. Accept. I love accept questions. So, this is an accept question. Nature of the procedure. Procedure risk. Cardiovascular risk. Patient fall risk. Or the neurological risk. So, which one will we not consider when stratifying blood thinners? So, we have already seen this is a very smart audience, and almost everybody got the correct answer, which is patient fall risk, whereas patient falls are, again, a very high-ticket item nationally for healthcare. In this particular context, patient fall risk is not an issue, although we do talk about elderly patients being on warfarin out there in the community. And those 80, 85, 90-year-old patients who are on warfarin for one reason or another, usually sometimes for not a good reason, they are at exceptional risk for fall and hematomas and brain and cranial injury from that, but that's a separate discussion. The risk of bleeding is highest during which of the following endoscopic procedures? So, we discussed low-risk and high-risk endoscopy procedures early in the talk. So, is it highest in diagnostic EGD, flexible sigmoidoscopy with argon plasma coagulation, colonic polypectomy, such as an EMR, or Barrett's radiofrequency ablation? This is a slightly more difficult question, but where is the bleeding risk highest? So, again, the majority of folks have said the correct answer, which is colonic polypectomy. Amongst this, in this group, that is the highest risk, even though that in itself is not a super high risk, compared to other things we do, but colonic polypectomy is the correct answer. As I already mentioned, in the recent years, ablation has moved from high-risk to low-risk, and diagnostic EGD and flex sig with ablation is always low-risk procedure. Thank you very much, and we look forward to the next talk.

antithrombotic agents

GI endoscopy

myocardium

GI bleeding

risk stratification

anticoagulant agents

thromboembolic risk