William H. Matthai, Jr., MD, Professor of Clinical Medicine at Penn Medicine discusses new research and clinical updates in antithrombotic therapies for COVID-19 patients. He elaborates on the evolving treatment guidelines and Penn Medicine’s recommendation for these patients.
Twitter @PennMDForum Dr. Matthai’s physician profile Endovascular Repair of Complex Aortic Aneurysms | Penn Medicine Coronary Artery Bypass 2020: Evolution of Practice | Penn Medicine the lab at? Sure. Um, but my interest is when my academic interest is anti probiotic therapy. And I thought I'd talk of things that I get asked questions about. Mostly one is, uh, when I thought is important, actually, is the co vid anti thrown biotic guidelines because they have the pen recommendations have changed pretty dramatically in the last two weeks. Um, and that times out well for the increase in our patient admissions. And then they tend to be a bunch of questions. Still about the no acts. I was gonna throw some talk some a few minutes in about that at the end, but there's certainly time for questions. Um, but for the covert stuff just to start off with, we certainly recognize that they cove in patients are hyper coachable. They have a higher risk of trauma bolic events, especially in i c. U patients. In spite of typical prophylactic Lovenox, Um, the issue is that most of the data is based on expert opinion rather than on lots of randomized, placebo controlled trials. And so the the recommendations air, clearly evolving as more data becomes available, is this is an evolving things you'll see today. What we do know is that risk of thrombosis increases with the degree of illness. The sticker you are, the more likelier to clock the markers of abnormal coagulation of common, uh, virtually uniformly elevated di di MERS and vibration levels. Uh, PT PTT tend to be preserved. Playlist tend to be preserved, so it's not a D. I C. Picture. Um, but it's important to recognize that we don't use thes labs to guide care in terms of antique robotic therapy. So getting a quantitative d dime er really does not add a whole lot to the management of the patients. As in many of these cases, Venus thrombosis is much more common than arterial thrombosis. Although arterial thrombosis he's clearly a problem and bleeding is rare, is relatively rare. Um, due to the cove to cove it alone, there is an anti fost Philippine type syndrome, which can cause an elevated PTT on. If a patient doesn't have a history of this, that they come in with an elevated PTT, but they need anti throw biotic therapy. It's not an indication to avoid anti coagulation, so a very small number of these people will come in with an elevated a PTT and still require any coagulation. The things that's evolving is that the risk of thrombosis is not as great as we had thought. It waas If you look at the risk of thrombosis and covert patients and you compare it to the risk of thrombosis and non anti coagulated hospitalized patients before the day is the historical data. Before he started using DVT prophylaxis, the number of traumatic events in the cove in patients is not dramatically higher than it had been before. It is higher, but not dramatic. And so the risk is not is great. But the thing that we found more recently is it. The bleeding rate is higher than we had anticipated in patients who received any coagulation on DSO. If we look at some data from Penn, um, it's not published yet. But at a 433 443 Covic patients, about a third got therapeutic and coagulation. In this population There, there is about a 2 to 1 incidents of venous thrombosis, a za post arterial thrombosis, and about half of the Venus Trumbo sees were pulmonary emboli. So pretty significant events, but probably most surprising, and this is really the first trial that we know of that has shown. This is that there was a 14% 7 14.7 risk percent risk of major bleeding. So bleeding in a big way G i bleeding, requiring transfusions, multiple grammar. He will go and drop into important things like joints. A za major bleeding was relatively common, much more common than we had thought. And so what this has resulted in is the less of a less aggressive anti coagulation as a recommendation. It is important to acknowledge, however, that every Covic patient, if they're not actively bleeding or particularly high risk, should have pharmacologic prophylaxis of some degree. So let's look at the old recommendations thes. They're not the ones we're looking at now, and the patients who have suspected or proven proving trump trombone bolic events. That's not going to change. If they have a low bleeding risk, it's going to be therapeutic intensity and coagulation, preferably with Lovenox. If they have a higher bleeding risk, you're gonna want to use unfair action. It'd heparin, um, because you can reverse it quickly. The place that's going to be the difference is if BT is not suspected. The chat The use of more aggressive anti coagulation, even in hostile, even in ICU patients is not going to be recommended. So here are the new recommendations. If you have a patient whose stable, there's a lack of any change, but in the the sick patients on the floor or the critically ill patients on the floor, therapeutic intensity anti coagulation is not considered unless they have suspected a proven VT. Um, and if they have a high bleeding risk, you're gonna Onley use standard, um intensity, not intermediate intensity, any coagulation. And so the degree of any coagulation is going to be dramatically less so what we use, um, so most of our patients are gonna have normal renal function on DSO. The standard intensity is the standard 40,000,040 mg. DVT prophylaxis does once a day. The therapeutic doses the standard 1 mg per kilogram every 12 hours, and the intermediate doses half of that. So it's more than the two and preferably using an ox, because there's no risk of hit and and there's no testing that's involved. You don't have to draw PTT s, um uh in patients who have covert as patients. Renal function deteriorates. There's mawr returned to unfair action. It'd heparin, um, because of the problems with clearance of e knocks. But still, the only place you're gonna get an infusion is up here for the patients who have the therapeutic intensity anti coagulation and have renal failure because you don't wanna have to go in and draw a lot of P t. T s. Another change waas that if patients were therapeutically anti coagulated on admission. Previously we had said Stop all anti coagulation. Unless the procedures plan, we still say continue warfarin because it can be reversed. It's not an easy transition necessarily to a no act or thio too, eh? Knocks on dso continue unless you need to have ah procedure. If they're on a no act on admission, we recommend transitioning to Lovenox because it's easy to do at the time of your next dose. You just give them a dose of Lovenox. Um and there are significant drug drug interactions with the no acts and some of the drugs that are used for treatment of cove it. And so if a patient on no act, we recommend transitioning to a low my Chloe heparin, whereas if they're on war friend, unless they're having procedure, um, continue the war friend. The other thing not to forget is the mechanical prophylaxis is still recommended in patients who can't get pharmacologic prophylaxis, and it can also be used in high risk. I see you patients who, in addition to their pharmacologic therapy, which would be either standard or moderate intensity therapy, not full those therapy unless they have another indication the other. The other thing is, your patients have to go to go home at some point, and previously we had recommended that essentially everybody get anticoagulants therapy on. That has definitely changed dramatically. We don't recommend that at all now for discharge considerations. If they're having indication for therapeutic and coagulation a valve DVT, a p e, something that they would require any calculation, continue it using the same guidelines. Otherwise, we do not routinely recommend use of extended prophylaxis in patients gone home after cove it if there are particularly high risk of Bte princess, they've had a procedure. They have been in bed for multiple days on their low bleeding risk, and they have normal renal function. You could consider extended prophylaxis. But the reason we don't recommend that is because the rate of Venus trombone bolic events in decoded patients once they get discharged is very low. And it's about the same is another populations that we don't routinely sent home on extended prophylaxis. And so if their patients with a high risk of bleeding but have low benefit, there's no role for that. But if you decide to use extended prophylaxis, the duration has been reduced to 30 days from three months on the jug choices, either going to be low dose River rock, Saban River rocks even 10 mg daily or n ox, 40 mg daily. Recognizing that that's not an FDA approved indication, so many papers patients now going home after Covic are not gonna be any calculated, which is a major change from previous recommendations. Other things we don't usually recommend routine screening for VT. So there's no reason for a C, T, P E and all these patients. There's no reason to do routinely to do Venus top. Alors, unless you have a reason to suspect that this may be an issue. The walking wounded those with covert, that air not ill enough to be hospitalized. Um, prophylactic. Any coagulation is not routinely recommended, but obviously have to still continue to be vigilant for thrombosis. Both arterial and Venus. Um, I don't object to aspirin the baby aspirin everyday for these patients. It's not part of the pen recommendations, because there's no data for it, But it's certainly used in, for instance, the orthopedic patients with to predict be de Vito D. V. T s post op major joints with a low blow bleeding risk. And if you do have to therapeutically anti coagulate, no accer preferred because you don't have to follow any any kind of testing. Um, but just have to remember, you have to look at the renal function in the drug interactions if you're gonna use it if you're gonna use no ax. So I was gonna just pause there there questions about cove it. And before I go into a little bit of talking about no ax, remember, everybody's muted. If you have any questions, you have to commute. Alright, I'll just keep going. So the the other things that I tend to get questions about are no accident, just term wise. No AC equals doh AC equals, so act Um And so I think, either No acrid oh, actor, the terms. They're mostly used thes days, so just don't get confused about that. You have to know a little bit about each of them, each of the drugs, and I would recommend that you sort of pick one that you know most about. But remember where the dough suggested is for the bigotry, and it's for 30. That's products. The River Rocks Band, which is Xarelto. It's a 50 a picks. A band, which is eloquence is a crack in it of 1.5, which is sort of silly, but that's the that's for the for the a fib, dozing the dose change. Otherwise, it's a crafting clearance of 15 for not a fit communications. Um, it's important to recommend that Iraq's about is given with food, and the bigger trend is not given is given, not with foods. You have to tell patients to do that daily, And when you're thinking about adjusting the dose, I mean think we're pretty comfortable with the standard dose off 1 50 twice a day for the bigotry and 20 mg a day for Barbara Rocks even and five twice a day for a pixie ban. The adjusted dose is a little tricky for River Rocks, Ebanks. It's not half of the other dose, which is the one for the other other, too. Because there is a 10 mg tab you could easily right for the wrong thing and not necessarily get it picked up. So you've got to remember that the 15 mg is to reduce dose for Roxy Band if they were crafting clearance less than 50 uh, as a intervention list. We often think about triple therapy, which is an Orlandi question, plus aspirin and Plavix, and we try not to do that unless you really need it. And a lot of the data was with warfarin, aspirin and Plavix. But now there have been three trials looking at the other agents, Uh, and you could use the biggest Tran with three dual. That's 150 mg twice a day. The standard dose River rocks a ban, which is 15 mg a day, plus Plavix. When the pioneer try a Laura picks, a band is 10 mg twice a day plus Plavix. The thing that you're gonna note here is that if you're really thinking about treating thes air typically patients in a fib. If you're gonna think about using drugs that for which there is data for using on an equal it in a fib, you're gonna want to use the Big A Tran or a picks. A bad, because there's data for using 15 mg of, uh, river rocks a band for a fib. It just isn't there on DSO. It may as well use the dose that's been used for a fib and add Plavix. The other thing you'll notice is that we try to avoid aspirin. And if we have to add a second anti platelet anti platelet drug in addition to aspirin, it's gonna be Plavix. It's not gonna be a tire. Uh, not gonna be Berlin, tha or, um, prostate grow because they're those really increase bleeding. So if you have a patient who comes in on oral anticoagulant therapy plus aspirin and they need a second anti pleasant agent, it's got to be Plavix because otherwise you're really increasing the bleeding risk. And we see a lot of patients that come in, uh, from other places, and they're on the Big A Tran and aspirin and Berlin tha and The first thing we do is stop the Berlin tha Onda put put on Plavix and hopefully stop the aspirin. Thea Other thing that's changed a little bit is the availability of and exa at shore. So if you think about any reversal anticoagulants that if you have war friend and life threatening bleeding. The preferred reversal agent is Aziz pro thrombin complex concentrator. PCC Um and I think you have no go seven, Captain, which, when you have it, sure. But PCC is the pervert one. It has no risk of infection. And has it's a low volume for the Big A. Tran. You have practice bind I protected. I like the other name idea uses a mob, but that is, uh, been around for a while. It's actually cost less than PCC on, but it's available. But and and Dexia and excellent Alfa was approved the end of last year, and it rolled out very slowly and sure now has access to it. Um, but it's important to looking at the reversal of no active and and excellent Alfa um is using the only data for use with River Rocks band and A picks a band there No data with other drugs, and it's on Lee for life threatening bleeding. It's not like I'm taking this guy to the O. R. I need to reverse it. It's not appropriate for that. It costs 30 to $50,000 a dose, so think about it before you use it. And it looks like there's a risk of an increased risk of thrombosis. When you use that drug idea, your idea uses a map. Your practice bind works for the bigotry, and and it can be used both for bleeding as well as for emergent surgery. Eso It's got, ah, larger, a broader indication for use, and it does not have that risk of thrombosis that and Dexia has. So if you're using and exits reverse, it's great. If you have a calm patient, comes with an intracranial bleed. That's the time to use it, Um, but if they come in and they say we're going to take the repair their hip, well, then you probably have to use PCC. People often ask patients going to Caffe. What do we do? Are going to procedure. The the question is, Do we have to bridge them? And the answer is no um, with a no act because all you have to do is stop the drug at the appropriate time before the procedure. The half life is short enough that they're gonna have a very short period of time that their own anti coagulated Um and they're different. They're different criteria depends on the risk of their bleeding there renal function on the type of surgery that they're having. Uh, in general, we consider Cath low risk of bleeding. So we for most patients will say 48 hours for really, for everything. For calf. It makes it easy, easy for everybody for each of the drugs. But we can do it for less than 24 hours, particularly if patients have been on River Oxy Band and feel comfortable about using it. If they do have significant renal dysfunction, the duration of discontinuation is significantly increased. You see 96 hours, so that's four days for a patient who has going to major surgery and in the bigotry, and it's even longer than that. And so so if you have a patient that's a different renal dysfunction there indictable the biggest trend and they're going to major surgery, you've got days Thio wait before they could go to surgery. But that's a complicated slide. You can remember that. But there is a nap. Actually, that's called Manage Antique OAG. So if you haven't put it on your phone, it's a good thing to do. It's really it's got lots of, um, calculations. Lots of advice. Andi, all you have to put in is what procedures being done, Some basic information about the patient. And we'll tell you when you have to stop the drug part to the procedure. And it's a great little thing to have on your phone and to use. Um And so that's the last thing I had. I don't know if anybody has any questions at this point. Remember your beauty. Hi. Hi. Any any questions? You Can you hear me? Yeah. Yeah. You know, uh, we listen to your first presentation about the Kobe 19. Uh, you got a little bit confused, you know, like for for the typical patient with Kobe, um, that they are respiratory wise. They are sick, but there is no evidence off blood claw. And they have it like a uneventful course. You know, go home on oxygen or something. else. What is your recommendation for giving them anti coagulation? Is it that you have to give them like a prophylactic? Those if you think that if they've been in bed for a week, um and they're not going to be very mobile once they get home, they got normal renal function. Um uh, at then you can probably give low dose. Anti coagulation is you can't give them Lovenox 40 mg a day or river rocks band 10 mg a day. But if they are, you know, they've been in the hospital for a couple days and they're ready to go home and they're able to walk and talk and get around. We would say, Probably don't give them any any coagulation when they go home, which is a big difference from what we have been saying a month ago. Read it. Okay. And what about the you said in your slides that there is no routine check off the inflammatory markers so we don't use that anymore? Correct. We don't. I mean, there's some people that used the inflammatory markers to predict the course of disease. Um, but you say you shouldn't be using it to say this person is at a higher risk of thrombosis, and therefore they should We should change their anti coagulant therapy. Um, it doesn't correlate necessarily. You know, it's not like if you got if you got a d dime er and it was normal, I guess that would be reassuring. But if you've got a d Diamond and it wasn't normal and the vast majority of covert patients, it's not going to be normal. Then you're not going to know what to do with it. Um, it's not gonna help you at all. So we don't routinely checked You die MERS cov patients. Okay. Okay, great. Thanks. All right. Well, if you think of other questions, you know how to find me. I'm in the cath lab interval. Should get you my email address, uh, my phone number, but in closing, I'd like toe. Thank you all for the support for the cath lab. It Sure, Justus. An update is in spite of the assuming, we don't get close down again. We're probably going to be pretty close the last year's volume or exceed last year's Catholic volume. In spite of the several months that we were closed down because of increased buying recently. And so we appreciate your support. Thank you very much. And have a good day. Okay, Thanks so much. Uh, would you be able to send me the slides to that presentation so we can send it to the group that has, um, and she'll send it out? The other thing I was gonna have hurt we can send out is there's a There's a one page cheat sheet for the new recommendations for any quiet from biotic therapy during Colbert. And we'll send you that Also, that would be perfect. Thank you very much. I appreciate your time, Carol. I don't have your email. Okay, Let's see. Yeah. Kot e l e s at sure. Physicians group dot com. Okay, great. I'll get all that out to you. Okay. Thank you, Linda. All right. Thank you, everyone. Thank you. Have a good day. You too. Thank you.