Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. Narrator - ? 00:11 This podcast 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 75 I'm your co host, Dr. Kane. I'm Dr Speaker 1 00:35 Schuman, and I'm Dr. Patel. And during the previous episode, we talked about perioperative management of anticoagulants and antiplatelet that was number 74 we are continuing the same talk in this episode as well. So I think we ended somewhere in talking about what to do with specific anticoagulants. Let's move to what to do in regards to antiplatelets, because these also require some holding around the procedure time because of increased risk of bleeding. Dr. Sean Kane 01:03 And you know, the most common anti platelet that should come to everyone's mind is aspirin. What's unique about aspirin is, even at doses as low as something like 50 milligrams a day, you can get a good amount of anti platelet effect. And really it's that's where the ceiling effect is. So giving 325, or even 650, of aspirin gives you no more antiplatelet effect. So even that baby aspirin, which is probably a misnomer because we don't use it in babies, even that baby aspirin dose gives you profound antiplatelet effect. Speaker 1 01:33 Yeah, so the recommendation about aspirin around the procedure is going to be irrelevant of the doses of the aspirin itself. We do know that there is longer inhibition of platelets with aspirin, so the recommendations are really divided based on what's the patient cardiovascular risk, because, as you said, Dr. Kane, most of these patients are taking it either small dose or higher dose based on some cardiovascular indications. So if they have low to no cardiovascular risk, and the procedure is low risk, things like minor Dental, dermatology or ophthalmology procedures, the recommendation usually is to not hold but if the procedure risk is moderate, too high, and the patient's cardiovascular risk is low or none, then in that case, we go ahead and Hold it for seven days before the procedure. And a Dr. Sean Kane 02:22 great example of this would be someone who's just taking aspirin because they think it's heart healthy, but has never had an ascvd event. And if you calculated an ascvd score in them, it's not very high. So this would be the person who decided to take aspirin because they felt like it was a good idea, versus that higher risk cardiovascular patient who is taking aspirin because they had a recent mi they've had stents recently. They had a history of CABG. Anyone who has basically ascvd That would be a high risk patient that you would actually not stop the aspirin in that patient, regardless of the bleeding risk of the procedure, with maybe some caveats for something like neurosurgical elective procedures, but for the most part, you're not going to be holding this. Speaker 2 03:03 Moving on to the next class of medications — P2Y12 inhibitors. The main thing we look at is monotherapy versus dual antiplatelet therapy. For low-risk procedures, monotherapy with agents such as clopidogrel, ticagrelor, or prasugrel usually does not need to be held (examples: cataract surgery, colonoscopy without biopsy). However, for moderate- to high-risk procedures (areas with high blood flow or where hemorrhage has severe consequences, e.g., the brain): clopidogrel or ticagrelor should be held for 5 days prior to the procedure, and prasugrel should be held for 7 days prior. Dr. Sean Kane 03:59 lot of these durations. And these are actually similar durations for if you were to hold aspirin as well. It's not actually so much the drug Half Life per se. A lot of times it's this irreversible platelet inhibition, where the body has to make new platelets for your platelet function to return. So it's one of those examples of a pharmacokinetic half life versus a pharmacodynamic effect. Those are different concepts here, yep. Speaker 1 04:21 And as we know from going back to knowing platelets, is that it takes them about seven days. That's like usually the lifespan of the platelet. So body needs to generate new platelets. Dr. Schumann, you mentioned something about whether patients are on dual anti platelet therapy. So these are patients who have received a stent and they're within that one-year duration. We most likely have these patients on something called Double or dual anti platelet therapy, and that is one of the agents is aspirin. The other agent is one of these p2 by 12 inhibitors. And so in that case, what we do, because these patients are high cardiovascular risk patients, we continue aspirin, as we discussed earlier. And. Most low to moderate risk procedure, but we consider holding the p2 by 12 inhibitors in cases of the high risk elective procedures. What the usual recommendation — from ACC/AHA — is that, if possible, elective procedures should be delayed. The delay depends on the type of stent: ACC/AHA says delay about 6 weeks after a bare-metal stent and about 6 months after a drug-eluting stent. Speaker 2 05:39 And again, the one caveat, though, if it cannot be delayed, if you said, you know, this procedure elective, but not really, we need to do it. Aspirin should be continued for drug-eluting stents, and the P2Y12 inhibitors should be restarted as soon after the procedure as possible. Dr. Sean Kane 05:53 And I think it's just worth noting that for these really high risk people, where they're on dual anti platelet therapy after a very recent stent where our main concern is actually stent thrombosis. So we have this like foreign object in a coronary blood vessel, and that foreign object has no problem clotting off, and if it does clot off, it can cause a profound MI for the patient. So really, it's not just people with cardiovascular disease. It's this really specific patient group because of this foreign body that they've had inserted in their coronary vessel, we're extremely worried about them, and that's why we may be deferring or delaying a potential intervention that isn't necessary right now for those patients, Speaker 1 06:31 absolutely and then. So segueing from what to do with different anti platelets, let's talk about in almost general situations, when do we resume either the anticoagulants that we discussed in previous episode or the anti platelets that we just discussed now? Speaker 2 06:47 So the recommendation generally for warfarin is 12–24 hours post-procedure. ACC/AHA recommends restarting about 24 hours after the procedure. And I know just thinking back to a patient I was talking to last week in our general practice. That's what we do. If we have, you know, let's say you take the medication in the morning. You know, we have a 10am to noon or, you know, let's say it's a shorter procedure. Go ahead and start at the net in the next day. So essentially, giving that 24 hour post procedure. And the one caveat we have in our clinic, again, is obviously, as you're looking for signs or symptoms of bleed. So I wouldn't recommend restarting unless you get further input from the hematologist, cardiologist, or the urologist, based upon how the procedure went and other patient-specific factors. And so I think that seems to be a kind of little bit of a nuance that allow the patient that we concurs that communication piece. Speaker 1 07:37 And if you really think about it, if we had to hold warfarin, we were holding it for five days, so by the time the procedure day comes, the INR level is usually one, and knowing the pharmacokinetic and dynamic of Warfarin even if they start that very evening, so it's within that 12 hour window that dose is not going to start being effective. So it's okay in certain cases, like colonoscopy was at eight in the morning. They can totally take their dose at night, that night itself, and Dr. Sean Kane 08:05 then transitioning to the antiplatelet agents like aspirin and our P2Y12 inhibitors (e.g., clopidogrel/Plavix), you can typically restart the day after the procedure. These do have an onset essentially as soon as you take them, within an hour or so, so you will start having the antiplatelet effect fairly quickly. Just to give kind of a typical clinical scenario would be someone who had open heart surgery. You know, these kinds of patients will have chest tubes to help with preventing a pneumothorax. They've got their chest was just opened up. We'll actually give them aspirin the very next day, potentially, you know, up to 12 to 24, hours after their surgery, after this fairly high bleeding risk procedure. Because again, it's a risk–benefit thing: they have pretty severe coronary artery disease, which is why they had the procedure in the first place. So if you can do that in someone who had a CABG, you can probably do that for someone who had a dental extraction, for example. And in a lot of the Speaker 1 08:59 situations, clinical judgment is going to play a big role. Risk versus benefit of thrombosis and bleeding is going to play a role as well. Speaker 2 09:07 Yeah, I think that applies again to our next situation. We talk about the doacs again. The big piece with this is we have some some nuance. So assessing the hemostasis and the renal function of the individual letting that know again, how soon you know these drugs again. We don't have that, that delay in effect, play with warfarin, so we have to factor that in. If initial immediate hemostasis is achieved, at that point, can resume, resume the medication within six to eight hours. But other moderate to high risk procedures again. So if we're talking as Dr. Kenn Jim is somebody who has had, you know, fairly complex, we've still got tubes in place, or the individual is still healing, and there's some concern about some internal bleed resulting from the procedure, probably better to wait and resume 24 to 48 hours later. And again, that's very nuanced and requires clinical judgment. And based upon the assessment, not just the pharmacist who makes that initial recommendation, but also based upon the the surgeons. And the consultants, everyone else who's participating in the patient's Speaker 1 10:03 care, the unfractionated heparins we covered during last episode, we talked about how they're kind of like an on and off switch used mostly in the hospitalized patients. So again, the evaluation will be obviously based on the procedures and patients bleeding risk for low risk of bleeding, you can resume the heparin within six to eight hours. For those with moderate to high risk, we can resume it within eight to 12 hours post procedure. Mind you, these patients are going to be under close supervision, and so really it's going to be dependent on the patient's bleeding risk. Dr. Sean Kane 10:36 Then finally, for LMWH, fondaparinux, argatroban, and bivalirudin — most of these agents are used in the inpatient setting; some (like fondaparinux) can be used outpatient. But for these guys, you know, if it's a low risk procedure, we can start six to eight hours after the procedure. And if it's a moderate to high risk procedure, in terms of bleeding, you could wait up to one to two days after the procedure itself. Yeah. Speaker 1 11:01 So a good example of use of Lovenox on the outpatient side is usually doing colonoscopy type bridging, and so I usually have patients start their Lovenox dose like the next day after the colonoscopy is over. The recommendation we mentioned earlier are more for your elective procedure. So you have time to decide. You know when you want to stop the medication, when you want to resume the medication, but there are situations like urgent procedures. So what do we do? We're not going to go in detail and talk about these agents, but it's worth a mention that we do have some reversal agents available that the clinical team may be utilizing in order to reverse the anticoagulation. Dr. Sean Kane 11:38 So with warfarin, we may give fresh frozen plasma (FFP) or a product called Kcentra (a four-factor PCC — prothrombin complex concentrate). This gives the patient back clotting factors that they're deficient in because of warfarin immediately. In addition to that, if we want their INR to stay low after that is given, we'll give them either an IV or an oral dose of vitamin K, depending on if they're actively bleeding or not, and kind of the clinical scenario. So basically, we give them a short term fix for their INR, and then a longer term fix for their INR, Speaker 2 12:12 And with dabigatran (Pradaxa) we have a unique option — one of the NOACs/DOACs that does have a specific reversal agent. We have idarucizumab (Praxbind), which can be given to fully reverse dabigatran, separating it from other DOACs. Speaker 1 12:32 For other DOACs, a specific reversal agent may not be available; currently clinicians may use four-factor PCC (Kcentra) to manage reversal when indicated. Dr. Sean Kane 12:46 So, you know, we've gone through a lot of material. I think it would be a great idea to go back to the original patient case from Episode 74 so this was a 55 year old African American female who was on Warfarin for recurrent vte, and she's currently got an INR goal between two and three, she's been fairly stable, and she's currently being evaluated for a knee replacement surgery. It's going to be in two weeks. And basically we were tasked with coming up with a plan for this patient in preparation for her procedure, in two weeks for her knee replacement surgery. Speaker 1 13:17 So if you kind of take that more of a process, like structure, the first thing to do, or step one, is to assess the patient's risk of thrombosis and the risk of bleeding. And mind you, we have to consider the risk of procedure related bleeding as well as patient factor for bleeding as well. So here looking at why patient's taking the Warfarin to begin with, it's recurrent vte, the last DVT she had was about seven years ago, so that wasn't like in the last three months, or even last six months. So considering that her risk of thrombosis can be somewhere between low to moderate, then Dr. Sean Kane 13:52 of course, we have to think about the bleeding risk for the procedure. So it turns out, and I'm not a surgeon, but I've heard that a total knee replacement can have a fairly high risk of bleeding associated with it because of the amount of manipulation that they're doing. The actual procedure itself is just at a high risk for bleeding. Speaker 2 14:09 Again, anytime you're hacking into a limb, it just, it does seem you're going to be getting some blood flow that may be triggered there. So yeah. So what we know about that is warfarin, plus a high risk procedure seems fairly would require a five day hold of the warfarin. So the question then, I think, becomes, what do we do? Then, in the meantime, do we just stop the warfarin? Go kind of five days without anything hope for the best? Do we put something else in there? So, Dr. Patel, what are we thinking? Speaker 1 14:33 Well, given kind of low to moderate risk of clotting, we can consider bridging with the low molecular weight heparin, and depending on you know whether you want to be aggressive and do therapeutic low molecular weight heparin, or you want to do more like a prophylactic dose, it really depends on the clinician in this patient. I think we can go either way, knowing that the risk is low to moderate, but definitely we'll have to do the bridging before and after the procedure, and then usually we stop. The warfarin, and then when the INR falls subtherapeutic (usually in 1–2 days), we introduce low molecular weight heparin. And then the patient will go through the low molecular weight heparin regimen, have the procedure, and we typically resume both warfarin and low molecular weight heparin about 12 to 24 hours after the procedure. Dr. Sean Kane 15:19 And again, thinking about this particular patient, someone who may be immobile for a prolonged period of time, her clotting risk is going to be higher in terms of a DVT than someone who's never had a DVT in the past. So in terms of risk assessment for her post knee replacement, I probably would argue more on the aggressive side, because of her past medical history of having a DVT. Turns out, actually, a lot of DVTs, you never recanalize the vein itself. So many patients will basically have a chronic clot in there that never goes away depending on where the clot is and how large it was. Of course, that's excellent substrate for a new clot to form off of. So again, she's at definitely a high risk, right? Speaker 2 15:59 So the next thing to do is look at what to do with her aspirin. And so again, here we're talking about primary prevention. And so because of that, again, we not looking at secondary history. We don't have quite that history of MI. So because of that, we can go ahead and stop the aspirin seven days prior to the procedure, Speaker 1 16:15 and then with any kind of bridging or gap in therapy, we'll have to do a very thorough patient education, provide a comprehensive plan. What I do in my clinic in general is put down the days, the dates, the timing of either the warfarin or whatever that we are bridging with, whether it be a NOx apparent or delta parent, and then educate them on the administration of these injections as well. Because I've gotten fair cases of patients saying, Well, I'm bruising, so I'm going to stop taking it. And that's where the risk of clotting and that stressing that you need this medication so you don't clot around the procedure is very important. And as we mentioned earlier, that this is more of an interdisciplinary affair, so not talking with the patient does really help, but documenting this plan that you have developed in the chart is helpful for those who are going to be taking care of the patient on the hospital side or helping patient post up so those caregivers are known. Would know, you know what's what's the patient's dose? You know what the patient needs to do? Obviously, the surgeon or the inpatient team is very capable of taking care of the patient's needs depending on the patient's bleeding risk or clotting risk. So the plan may be slightly modified. Dr. Sean Kane 17:28 So to kind of wrap up a couple key concepts. One concept, a big takeaway, is in terms of holding aspirin, it depends on why the patient is taking it. So if it's for primary prevention, someone who doesn't have an extensive cardiovascular risk, you just stop it period. No matter what the bleeding risk is. If they're at a higher risk of cardiovascular disease, especially if they've had a recent stent, you're generally going to continue the aspirin with very few exceptions for very, very high risk bleeding procedures. Speaker 1 17:54 And as for restarting the anticoagulants or anti platelets, you know it's going to depend on patients hemodynamic stability. It's going to depend on the thrombosis risk, but it's also going to depend on how fast these medications start working and producing those anticoagulant and anti platelet effect Speaker 2 18:11 and again, one other point to make is the idea that what we're talking about here, generally, is in terms of elective procedure, when you have the ability to plan out and carefully weigh risk versus benefit of bridging. No bridge how long to hold for a number of procedures that are more emergent in nature. We do have that ability to provide a degree of block or a reversal of the agent. Again, that's going to depend upon the individual agent we're referring to. We do have Kcentra for some DOAC reversals, and we have Praxbind (idarucizumab) available for dabigatran. And then we also have FFP and Vitamin K and another mention methods for reversing warfarin, for example. The big thing to know, though, again, with all this is, this is an interdisciplinary dialog piece where you're communicating with number providers. The you know, the surgeon may reach out to pharmacy to ask for input. We communicate it back to them, write a note, defer to them, and again, they have the ability to kind of, there's a little bit of a nuance to it as well. Can we consider relaxing it or tighten it up a little bit? And then the next piece, obviously, is to involve the patient in that decision process, give them the education, and then also make sure that they're communicating again with the last provider that sees them, the surgeon to make sure that nothing coming out of the procedure may have changed your plan based upon any emergent bleed that may be seen or other complications that were noted from the procedure. So it's kind of an ongoing dialog needs to be there. Dr. Sean Kane 19:33 So that wraps up our perioperative anticoagulation and anti platelet topic. If you haven't done so already, check out episode 74 which is where we kind of kicked off the topic and covered a lot of the anticoagulant aspects of this topic. If you want to see show notes, we're at HelixTalk.com also on Twitter, at HelixTalk, and we love those five star reviews. Keep those coming. So with that, I'm Dr. Kane, I'm Dr. Schuman, and Unknown Speaker 19:57 I'm Dr. Patel, and as always, study. Board. Narrator - Dr. Abel 20:01 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 - ? 20:12 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.