← The Curbsiders Internal Medicine Podcast
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- [00:00]
A
Hey, listeners, you're about to hear an unlocked Patreon bonus episode that usually doesn't appear on this feed. And I would love for you to check this one out and then go over to our Patreon and sign up@patreon.com curbsiders because we have over 60 bonus episodes where Paul and I recap these high yield episodes with our favorite pearls. Then we answer some listener questions and we give our picks of the week. It's delightful and you're gonna love it. And for this episode you're about to hear is it's very timely because the headlines just came out yesterday. Adexanet Alpha has been pulled from the US market. That's the reversal agent for Factor XA inhibitors. We talk about it a little bit on this episode. We talked about how they found increased rates of thrombosis. And just last week the FDA updated the safety of Adexanet Alpha and saying that they found in the Annexa 1 trial that that there was an increased incidence of thrombosis that was almost double in the treatment group versus the non treated group and thrombosis related deaths at 30 days in the Adexanet Alpha group. So it has been pulled from the US market. It may still be available in other countries, but wanted you to listen to this with that in mind that there's been a major change and that will no longer be used in the US and AstraZeneca is no longer selling it here. So with all that said from myself and the entire Curbsiders team, I want to wish you and your family a happy holiday and happy New Year and I hope you enjoy this episode. Paul, how do you feel about food puns?
- [01:35]
B
I'm fine with them. Find something about any puns? I guess.
- [01:39]
A
All right, well, I went to a seafood disco this weekend.
- [01:48]
B
No, I'm not gonna get this one either. All right, tell me more.
- [01:51]
A
But I got injured. I pulled a muscle.
- [01:56]
C
Oh.
- [01:56]
B
So the disco's kind of a little bit of a false. It's a little bit of a misdirect there.
- [01:59]
A
Well, the seafood disco, Paul.
- [02:01]
B
Sure, yeah. No, no, I get the seafood part.
- [02:03]
A
All right. All right, one more, one more. This one. I don't know if it's better or worse. Someone threw cheese at me.
- [02:14]
B
I hope people are watching this on video just so you can see the face he said. We made that O. Tell me. Go ahead.
- [02:20]
A
Real mature.
- [02:26]
B
I don't even know that I get that one. No, those are the words you said. How is that a cheese pun?
- [02:35]
A
I Guess someone threw cheese at me. It was real mature. I don't know. Doesn't cheese mature?
- [02:49]
B
The fact that you flipped through 30 cards and laid it on that one is incredible. All right.
- [02:55]
C
The Curbsiders podcast is for entertainment, education and information purposes only, and the topics discussed should not be used solely to diagnose, treat, cure or prevent any diseases or conditions. Furthermore, the views and statements expressed on this podcast are solely those of those and should not be interpreted to reflect official policy or position of any entity aside from possibly cash, like more hospital and affiliate outreach programs, if indeed there are any. In fact, there are none. Pretty much. We aren't responsible if you screw up. You should always do your own homework and let us know when we're wrong.
- [03:20]
A
Welcome back to the curbsiders. I'm Dr. Matthew Frank Waddo, here with my great friend and America's primary care physician. Probably the primary care physician, at least that's what his mom tells me. Dr. Paul Nelson Williams.
- [03:35]
B
I don't think she's telling you this directly. This took a turn. Hi, Matt, how are you?
- [03:38]
A
Nope, we have a weekly phone call at this point.
- [03:40]
B
Paul, listen, you should. You would love her. She's delightful.
- [03:44]
A
I can tell she must be. She raised you. All right, well, this was episode on anticoagulation for venous thromboembolism. This was a bit of an Update episode featuring Dr. Tara Lech, who is a PharmD and she was from the Anticoagulation Forum, a great organization that we connected with to produce this episode. Production was done by med student extraordinaire Ben Fuhrman. So thanks to Ben for that. And Paul, let's get into it. How are we choosing our doacs these days when someone comes in with a clot?
- [04:21]
B
Well, Matt, by and large, it seems like we're picking a Pixaban. I will expound. At least in my area, Matt, the debate is always Pixaban versus River Rock Saban, and some of that is driven by insurance coverage. But if all things being equal, there's a great figure in the show. Notes to kind of an algorithm to go through. If there is some degree of renal insufficiency, you need to dose adjust rivaroxaban, so you might favor apixaban for that. If they have intact kidney function, you could go dealer's choice. And then if they are at higher risk of bleeding again, that would maybe favor apixaban over rivaroxaban. There's actually a trial that's not even been published yet, but watch the skies. That Seems to show just fewer bleeding events with apixaban compared to rivaroxaban. So in general, apixaban, if you can get away with it, just seems to be kind of the easier choice. But if they have intact renal function and average or low risk of bleeding, then you could probably get away with either one.
- [05:12]
A
And that trial was the COBRA trial that Dr. Leck emailed us about afterwards. It was presented at the International Society for Thrombosis and hemostasis in 2025. And I guess people are excited about the results. Much lower bleeding risk with apixaban. So that's what we're doing for now, Paul. We have. So we have our choice. Apixaban or rivaroxaban. Dabigatran. I almost said the brand name dabigatran is not really used anymore. If you remember way, way back, we did our first anticoagulation episode. It was like one of the first three episodes. I remember Stewart being really like really hating dabigatran because it caused a lot of GI upset. And, you know, that was one of the reasons. The other thing is, if you want to use it for VTE, you have to use a parental agent for up to five days or so before you switch over to it, because that's the way the trial's done. So it's not approved the way apixaban is or viroxaban is to just, you know, you can start those in the ER without any sort of parenteral agent. So I think that's why that agent we don't really see much more, at least for VT el. Once in a while you'll see it for someone with afib.
- [06:29]
B
Yeah, I mean, the big selling point for the doacs was the convenience. Right Back when we practiced back in the Stone ages where warfarin was the big drug. The fact that you didn't have to monitor things, that's what made these things easy to have to refer to a parental agent to start just kind of undercuts that point a lot.
- [06:46]
A
And then we asked her, just trying to confirm why do we have these starter packs, these higher doses of the agents to initially after a clot. And it seems like maybe just that's because of how the trials were done. But also the thinking is, okay, we want to get people therapeutic more quickly and the risk of recurrent VT EL is highest, like it's front loaded. So like, as you get further out from the clotting event, the risk goes down, especially once you get beyond three months. So I think that's why you have those starter kits, those higher doses. And she said, you know, it depends on the person, like whether or not you count the days in the hospital towards the starter pack or if it's like if they got two days of a Pixaban in the hospital, you might just send them with the 10 day starter pack because it's just easier or less confusing for them. So a little bit of a kind of dealer's choice there, but it is something you need to think about. And then how are you settling on duration, Paul? Because you know, people are going to get diagnosed in the hospital, they're going to see you as America's PCP and they're, you know, if they're reading guidelines, it says three to six months. So what are you doing?
- [07:56]
B
Yeah, it depends on if you can identify clearly a provoked factor or not. That seems to be the differentiating line. So if someone has a provoked VT el, they've got a transit risk factor that goes away. So surgery sort of being the prototypical example of that, then you can get away with three months of treatment and sort of be done with it. If there's an unprovoked VT EL that is pretty probably, probably lifelong. Just because the workup tends to be sort of unsatisfying, it doesn't really yield you much unless you're suspecting specific things. So for me it's either like three months or lifelong and there's not a whole lot in between there. I'm not sure. What does your practice look like?
- [08:29]
A
Yeah, it's the same thing. I try to talk people out of hypercoagulable workups. Unfortunately I seem to meet the patient who was told in the hospital that they need a hypercoagulable workup. So, you know, they're already dead set. They're like they have a follow up with hematologist in three months and they're going to get the workup whether or not we think it's appropriate. But when would you think about doing that, Paul? Do you have like a patient in mind where you think it is helpful?
- [09:00]
B
Yeah, I mean it's. The antiphospholipid syndrome is really kind of the one that you're looking for just because that actually impacts management to some extent and those patients are often young and there's the pregnancy is part of the consideration for those. So the person for whom I might suspect antiphospholipid antibody syndrome would be someone who has unusual clots is one thing. Obviously history of lupus, whether personal or very close family member, they're Relatively young. And by unusual clots, I mean the dural venous thrombosis or the splanchnic thrombosis, that kind of stuff. Not necessarily just a bread and butter distal dvt. So those are the patients that would kind of prompt me to maybe chase that down specifically because it would impact how you would manage it and sort of how you would counsel those patients. But otherwise I don't do much in the way of the million dollar workup, as unsatisfying as that is for me as an internist who really wants an answer and a diagnosis.
- [09:50]
A
Yeah. And to remind people, if you are going to do the workup, you really should send the lupus anticoagulant before the person is started on therapeutic anticoagulation, which, I mean, I know that's hard to do in the hospital, especially when you're initially making the diagnosis. And if you're sending the anticardiolipin antibody and the beta 2 glycoprotein, those should be repeated. All three of those should be repeated 12 weeks later because it has to persist in order to make the diagnosis of antiphospholipid syndrome. So we have this person that has unprovoked VTE and let's say for whatever reason, they have an active lifestyle. They just don't want to be on chronic anticoagulation. So they're not. But now they're going to a wedding in Japan. Paul, what would you tell them? Would you treat this person, at least temporarily?
- [10:49]
B
I would have the conversation with them for sure. So if someone is at high risk of recurrence and they're doing this sort of high risk activity, which would be this sort of prolonged flight specifically. So there's the usual counseling that you just do for anyone who's going on long flights. You would tell someone like, you know, get up and walk around if you can. Make sure you're moving your legs. An aisle seat is nice. If you like an aisle seat, I prefer a window. We litigate that on the episode. But above and beyond those things, if someone is at high risk and they're not on medication, you can actually anticoagulate for the duration of the flight. So you can actually do apixaban 2.5 milligrams twice daily, or river rock band 10 milligrams daily while they're in the air. And the tip is just to prescribe the months worth so they have the medications for when they travel. But recognizing that probably few people are going to actually travel enough to actually warrant going through an entire months long prescription for.
- [11:36]
A
Yeah. And Dr. Connors, when we talked to her about this, made the point like if someone's like flying for 20 hours and they're going to be on an eight hour car ride and like you, you just want to see what their travel plans are because they might need more than just the plane flight. That's a great point of coverage as well. But yeah, this is something I don't know that I don't think I've actually had the occasion to do this yet. But I have mentioned it to people that were the kind of person that I would, you know, like they're like stopping anticoagulation. I'm saying, listen, but we, anytime you undergo a surgery or if you're gonna go on like a long ride, we need to talk about this because we may need to put you on medication to, you know, to make sure you don't have a recurrent clot. All right, Paul, another conundrum is this distal dvt. How do you handle those?
- [12:28]
B
I hate them so much, man. You shouldn't get the vibe.
- [12:31]
A
Why does that not surprise me?
- [12:33]
B
Because, you know, I hate uncertainty. And the scenario that I typically see is you have someone who comes in with concern for dvt, like they have a little bit of calf fullness and you feel like you see some asymmetry on examination. There's enough risk factors so you send them for the venous duplex study and it comes back with just a distal dvt. So the reason I struggle with this is because there are different ways to kind of handle it. So in isolated distal dvt, I think you even have the option of monitoring with serial ultrasounds in some circumstances. But when you read a lot of guidelines would advocate treating someone for symptomatic DVT that is distal. And my argument is always I wouldn't be looking for it if they weren't symptomatic. That's where I kind of struggle with. So I feel like most of the time I wind up treating these patients by they've defined themselves. But there are theoretically other avenues you could pursue, even though I don't feel great about any of them in particular, do you have, do you have a different algorithm or do you just agonize less over this particular thing? Matt?
- [13:25]
A
No, I don't have a different algorithm. I think I've had one person that like just sort of insisted on not being treated. And we followed with ultrasounds and it was hard because it was like they were supposed to get ultrasound weekly for a Couple weeks and they ended up getting like one, two or three weeks later. And fortunately it hadn't like extended a ton, but it was kind of a mess. So I think the easier thing is the patient's willingness to just treat them and because, I mean, if they were symptomatic, who knows, maybe they had like a small piece break off and it was bigger, you know, before you saw it. I don't know. But that's, that's kind of my thinking. Another, another area of uncertainty I had was if you. Because when you, when you look up on like a Lexicomp or something like that, they used to have these. Oh, for patients above BMI of 40 or 35, be really careful. And like almost all the patients in the hospital have BMI over 35 and then. Or very at extremes of weight, basically very low bmi, very high bmi, be careful. She told us that as long as the person's not more than 150kg, that for the most part it seems like there's a very wide therapeutic index for these agents and that patients are okay even if they're BMI over 40, as long, you know, so that, that's useful. She said the one group she does worry about is the post bariatric surgery because absorption can be different. So in those cases you might want to monitor 10A levels, which is something that I have not been trained to do, Paul. So I would probably be consulting with a hematologist for. Or a pharmacist like her for that.
- [15:09]
B
Yep, same.
- [15:11]
A
Yeah. What about this treatment failure? I mean, I don't really. Again, this might be one of those ones where the answer is refer. Actually, I know that's going to be the answer. Paul, talking with you, but in general, any advice for the audience or anything you remember about that from the conversation that you wanted to pass on?
- [15:33]
B
No, I mean, you know, my general practice, Matt, I feel like if I'm asking a question I'm not sure the answer to, that's what specialists exist for. So if someone had the treatment or medication and particularly a Doac, I would probably send the hematology because I just don't have comfort.
- [15:44]
A
Yeah.
- [15:45]
B
With the labs and the things to kind of chase down necessarily.
- [15:49]
A
But the main thing she told us is like, you know, try to really press them, like, how are you taking it? Did you, did you miss any doses? Has anything else changed? Any new medications, you know, something that could explain, like why it happened? Was it really a treatment failure or was it like a just an extenuating circumstance of some Kind. So let's see what else, Paul? I mean I think we've gone through a lot of this stuff. There was a lot more on this episode. But I really recommend people listen to the full thing if they haven't heard it because there's just so many different like nuanced things we asked her about and it's so it's hard to recap those in in this format. We did have a question, Paul, from some listeners and the first one I want to get to is related to this episode. So, Lynn, nurse practitioner asked for elective surgeries. Do surgeons typically manage and stop do typically manage anticoagulation? She said when she's worked on the inpatient side the surgeons always seem to do that. So what's your experience Paul, pre opping patients and who's managing the anticoagulation?
- [17:03]
B
I rarely see surgeons take ownership of this. I tend to get forms asking for permission or asking for advice about discontinuation or resumption of anticoagulation. So usually they're nice enough to reach out to me and sort of ask either a, is it okay to hold this medication for two days prior to surgery or a day prior to surgery or yeah, so basically I basically usually more asked about it rather than being told what to do with it.
- [17:29]
A
Same. And I mean in primary care we are pretty much relied upon to do this like when do you stop the warfarin or when do you take the last dose of low molecular heparin or doac and then in the hospital, I mean the time where I think you're seeing anticoagulation being managed, I would say it's more the post op prophylaxis for orthopedic surgery patients. I mean that's where the surgeons seem to have a really strong either I want aspirin or I want a rivaroxaban or apixaban, whatever. But those are usually the cases where I'm seeing a really strong opinion from the surgeon. But for the pre op visits it's really on us in primary care to manage that. And if it's a complicated case like antiphospholipid antibody syndrome, I've had multiple hematologists tell me you need to have me involved for that because these patients are at increased risk. And actually sickle cell is another patient that they want to see before surgery if they're being pre op ed as well. Not necessarily for clotting reasons, but. All right. And then we had one other question, Paul, this is from. How do you think you say this name Notrub Damus.
- [18:46]
B
Yeah, I think he got it.
- [18:47]
A
Notrub Damus. What do you think that refers to, Paul?
- [18:52]
B
I have to assume it's a pun on Nostradamus. Why? It would be no Trub. I don't know. Trouble, maybe. That's a. Hmm.
- [18:58]
A
Maybe. Maybe it's the last name. All right. Anyway, good name.
- [19:03]
B
Intrigued name.
- [19:05]
A
Okay, what about older adults with osteoporosis who may or may not have been on alendronate for some amount of time? They're not sure. Or had maybe a few doses of zoledronic acid, but they don't know the details. Like, how would you approach this situation, Paul? What say you?
- [19:27]
B
Yeah, I would probably start over, frankly. I would probably get the DEXA scanned and just kind of see where things are at and then just treat as I would for someone who I'm seeing it for the very first time. So there's osteoporosis, then. I would do what you do. Yeah. So I didn't have a terribly exotic answer for this. I would love to hear your approach because I need to be more nuanced than I am.
- [19:46]
A
No, not necessarily. I was trying to look up to see if there's anything like, can you. Do you just. Like you said, you just do a DEXA scan? I mean, if they have a new fracture, you would just treat. But the guidelines would say even if you knew they had been on it for certain before, you would still treat or escalate therapy. If someone has a new fracture while they're on alendronate, you would escalate to, like an IV agent or something else. So, yeah, I would do the same thing. And I did look this up. And I mean, basically, if their DEXA looks bad or if their FRAX score is bad and you're not sure if they've been treated, you would just treat them again. One of the, I guess, neat facts that I did see is that in studies of drug holidays from bisphosphonates, when people are on, let's say, 10 years of oral bisphosphonate or five years of IV bisphosphonate, they start to get this increased risk for atypical femur fractures. And the risk is it's overall low, like four and a half per 10,000 person years. However, if you wait 15 months, like 15 months of a drug holiday, that risk goes down to 0.5 atypical femur fractures per 10,000 person years. So it very quickly goes away. So, you know, in this scenario, that's one of the Main risks of harms of these chronic therapy. Right. So if this has been long enough, this person doesn't even remember if they took an agent or not. It's probably been more than 15 months, and that risk is probably diminished. So that's my smart answer to this question, Paul.
- [21:32]
B
Great. So you congratulate them for not being on therapy and then restart it.
- [21:36]
A
Exactly. All right, Paul, Picks of the week. Let me go first this time. Did I recommend. Did I talk to you about this? I'm reading a book by C.J. box, or. I just finished a book by C.J. box. It's about a game warden in Wyoming.
- [21:53]
B
No, it doesn't sound familiar at all.
- [21:56]
A
So a family friend is a guy that just tears through tons of books, and he's read a lot of these C.J. box books. The main character's named Joe Pickett. He's a game warden in Wyoming. And apparently there's a lot of violence and just wild stuff that happens there in this small Wyoming town where he lives. It's a lot of, like, animals and outdoors and hunting, and it's just a, you know, totally different way of life than what I'm used to. But the books are just these kind of entertaining mystery stories just in that setting. And I would highly recommend it if you. You want a mystery that's set in a different place than you're used to, at least for you and I, Paul, because I know you don't live in Wyoming and neither do I.
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B
Correct yet? Yeah, no, it sounds like a nice popcorn book. It sounds like a lot of fun.
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A
It is a lot of fun. How about you, Paul? What are you into?
- [22:56]
B
I am going to. To no one's surprise, Recommend Death Stranding 2. Matt, the 2025 video game that is the sequel, in case you couldn't figure it out, to Death Stranding, which was one of my Pandemic games. So it is again, I think it's PlayStation 5 exclusive, if I'm not mistaken. It's by this video game pioneer named Hideo Kojima, who is notorious for doing these video games that have these really convoluted plots and long cutscenes, and they get very complicated. So Death Training one. Matt, I'm going to talk too long about this. You can just flash the red light if I go on too much. Was my Pandemic game. It came out, it was made before the pandemic, but was released during the pandemic, if I remember correctly, or right before it began. And it's basically set in this future where the worlds between Living and dead collided and it caused this mass extinction event. And then everyone kind of hid underground and isolated themselves. And you play this porter, this guy who just sort of delivers packages from isolated location. Isolated location. So in the middle of the pandemic when the streets were empty and you're only seeing video calls and relying on delivery drivers, it's felt weirdly prescient and the plot just gets in here from there. So the sequel is set in the same world. You're still this guy who delivers packages. There's still this phenomena of the world of the dead and the world of the living kind of colliding and causing issues. I won't get into the plot because the plot's all gibberish Anyway. Matt, I will say it is the best looking video game I've ever seen in my entire life. There are bits of it that are as visually beautiful as any piece of visual art I've ever seen. Like, period, full stop. There's a scene that takes place in the land of the dead that's sort of at this riff 1 Mexico's Day of the Dead that is just jaw droppingly beautiful. And then there's another scene I'm trying not to spoil it too much, where one of the characters has a weapon that is a guitar that shoots electricity out of it. And in the middle of their scene, a gigantic samurai robot comes in and fights with them for like five minutes. And it rules. Like, it's just one of the most bonkers, bananas things that I've ever seen. The gameplay is fun. They sanded off all the smooth edges, the first ones. It is an unmitigated masterpiece. So if, you know, it's one of those things where, if you already heard of it, you probably played it, you know, but just in case you needed someone to kind of push you into it. Dust Training two on on the beach is Game of the Year. One of the best games I played in the past five years. Just an absolute masterpiece.
- [25:07]
A
Why were you playing such a sad, isolated game during the pandemic? Like, you should have been playing, like, I don't know, some online multiplayer game with like other, you know, talking. Talking trash to 12 year olds or something.
- [25:21]
B
You know, everyone's doing Animal Crossing. I don't know. The same reason you listen to sad songs after a breakup. You know, sometimes you just want something kind of reflects your mood and not necessarily bolster it.
- [25:28]
A
All right, Paul, I'll let that slide.
- [25:30]
B
Fair question?
- [25:31]
A
Yeah, fair question. Okay, let's get to an outro.
- [25:42]
B
The smoothest silk transition this has been another episode of the Curbsiders bringing you a little knowledge food for your brain whole. Yummy, yummy indeed. You can find our shownotes the curbsiders.com and sign up for our mailing list to get the weekly show notes in your inbox. This includes the Curbsiders Digest, which recaps the latest practice, changing articles, guidelines and news in internal medicine.
- [26:00]
A
And thanks as always to all of you, all our patrons for supporting us so that we can keep doing the show. We have a big team. We rely on your support. We truly appreciate it and we love doing the show. We're happy that we can keep doing this and I would also like to thank our whole Curbsiders team. Our technical production is done by Podpaste. Elizabeth Proto does our social media. Jen Watto does our Patreon. Chris the Chumanchu moderates our discord. Stuart Brigham composed our theme music and with all that, until next time, I've been Dr. Matthew Frank Watto and as.
- [26:33]
B
Always I remain Dr. Paul Nelson Williams. Thank you and good.
- [26:48]
A
Guys.
- [26:48]
C
Thanks for helping me carry my Christmas tree. Zoe. This thing weighs a ton.
- [26:52]
B
Drew Ski, lift with your legs, man.
- [26:53]
A
Santa.
- [26:54]
B
Santa, did you get my letter?
- [26:55]
C
He's talking to you Bridges.
- [26:57]
B
I'm not that.
- [26:58]
C
Of course he did.
- [26:59]
B
Right Santa, you know my elf Drew Ski here.
- [27:01]
C
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- [27:19]
B
Or give it as a gift.
- [27:20]
C
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- [27:24]
A
Nice.
- [27:25]
C
My side of the tree is slipping.
- [27:26]
B
Kimber.
- [27:27]
C
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