← The Fellow on Call: The Heme/Onc Podcast
The Fellow on Call: The Heme/Onc Podcast
Episode 133: VTE Series - Perioperative Anticoagulation Management and Emergent Reversal
Ronak Mistry, Vivek Patel, Dan Hausrath
Loading summary
Transcript36 lines
- [00:00]
A
Hey, friends. This episode of the Fellow on Call is not meant to be used for medical advice and is intended for educational purposes only. Patient information has been modified to ensure privacy. The views expressed in this episode do not necessarily reflect the views of our employers. Enjoy. Welcome to another episode of the Fellow on Call, the Hingmong podcast. We're coming at you from Berlo University Medical Center. I'm Ronak.
- [00:22]
B
I'm Vivek.
- [00:23]
C
And I'm Dan.
- [00:25]
A
And in today's episode, we continue on our journey, talking all about venous thromboembolisms. The this time talking about perioperative anticoagulation management and emergent reversal. Again, super high yield topics, things that inevitably will come up if you take care of anybody that's ever had a blood clot.
- [00:42]
B
Really excited to get into this one and reference our website for this because we're going to have all the details laid out for you. So if you ever need a quick reference for how do I reverse this anticoagulant or. I remember they mentioned something. Go check that out. We've really spent a lot of time putting this one together.
- [00:58]
C
Yeah, looking forward to it. This is stuff we do day in and day out. So in your hematology clinic, this is. This is kind of your bread and butter. So glad we're getting into it.
- [01:06]
A
All right, guys, without further ado, let's roll that show. So before we start off on today's episode with warmer weather around the corner, I think more so in Nashville than here in Philadelphia. Just curious what you guys have planned in the next couple of weeks. Anything exciting now that the weather is getting better?
- [01:24]
C
Logan and I are definitely getting back towards hiking and been already starting to get the grill fired up. Just some hot dogs last weekend, so hopefully a lot more of that coming.
- [01:34]
B
Yeah, I fired up the grill too. So have that. Which is always a good time in life. We've been picking up tennis a little bit more, so gonna play a little bit more tennis, which is, you know, it's been a fun new hobby. I'd actually never played tennis really before, so I've been having a good time doing it.
- [01:49]
C
I don't have to play you. I'm terrible. I'd really love to hit that ball around with you.
- [01:54]
A
Really jealous that you guys are able to grill. I was just telling Dan before this, we barely get over 50. We've got somehow wind blowing in every direction at the exact same time in Philadelphia. So although there are cherry blossoms out, it still feels a little bit too cold to do Much, but hopefully in the city, just a lot more farmers markets and things like that. Getting to enjoy walking around. And then we do head out to vacation in a few weeks in Morocco. So that'll be exciting as well. Transitioning then into our topic for today, which is gonna be all about perioperative anticoagulation management and emergent reversals of anticoagulation. Things that inevitably our listeners are going to experience at some point in their life if they ever take care of anybody that's on a blood thinner. And so I'm, you know, excited about getting into this one. Another topic that many of you have reached out to us to cover. And so here we are. So guys, do one of you wanna kick us off?
- [02:49]
B
All right, I'll kick us off today. And Ronick, I wanna say that was not a smooth transition. We went from Morocco to somehow talking about anti, you know, who wants to talk about anticoagulation? Re rehearsal after that? But here we are. So let's talk about the case. So we have a 58 year old man who has a DVT and PE in the setting of metastatic pancreatic cancer. He's currently on a DOAC medication, specifically apixaban or Eliquis, and is tolerating his therapy well about 2 months after his initial VT Eliagnosis. Remember, he had a DVT in his femoral vein and a PE as well. You get a message in your clinic in basket from his GI doctor saying that the patient will need to have his biliary stent exchanged in two weeks. Weeks. And wants to know how to deal with his anticoagulation around this procedure.
- [03:33]
C
Yeah, this is a major part of caring for patients on anticoagulation. We're very frequently asked to help manage the anticoagulant around the time that a patient might need an invasive procedure. It's always important to ask about planned procedures just at your yearly check in appointments. That's part of my routine care of patients on chronic anticoagulation. In addition to getting updated labs to make sure their medication is still safe to prescribe. I'm asking. Okay. And do you have anything coming up? Are you due for a colon colonoscopy this year? Are you getting a knee replacement anytime soon? You know, anything like that? And I do ask my patients that as these procedures come up throughout the year in between our appointments, if they could give me at least four to six weeks advance notice. It's not always possible, but I always like to have four to six weeks notice to try and Give me time to come up with a good plan and to make sure that all the relevant parties know exactly how, how it's going to go down, really. When it comes down to it, only the team doing the procedure truly knows the full extent of the bleeding risk associated with that procedure. So they have to tell me whether or not they need the blood thinner held during that procedure. If it's a really minor thing and they can do it without holding ac, great. If they need an extended hold before or after, they're the only ones that do that. And by that same token, they know when it's safe to reintroduce anticoagulation based on what they experience during that procedure. They experience more bleeding than they expected, or if ended up being a more complex procedure with a lot more sutures or whatever the case may be. You can always guide that team on how urgently you feel the patient needs to be put back on anticoagulation. But it's a conversation. They have to tell you what the risk of post procedural bleeding is. In general, procedure teams are going to want Warfarin or Fonda Paradox held for five days prior to the procedure. That should be enough time for the medication to wash out that INR to return to normal and for the procedure to be safe at that point. For DOAC medications, we have data from the PAUSE trial that suggests that a hold time of one day for procedures with a low bleeding risk or hold of two days for procedures with a high bleed risk should be safe. Should be enough time for that DOAC medication to wash out. Now, in practice, in my experience I've had, procedure teams tend to want us to hold that for five days, just like Warfarin, probably kind of a holdover from that long standing experience with holding Warfarin, a much older anticoagulant with a lot more experience behind it. But again, the recommendations are that you really only need a one or two day hold of that DOAC medication prior to going forward with the procedure. These medications are pretty quick on, quick off. And unless you're talking about a really high risk situation, like a resection of an intracranial tumor or some neurosurgical procedure like that, where the surgeon feels very strongly and has their practice, where they always hold their DOAC for a certain amount of time prior to that procedure, I want to be respectful of that too. So it's always a conversation and you have to make sure that you're working with those procedure teams to get the best idea of what's going to be best for the Patient with Lovenox, they like about 24 hours of washout period. So that last dose coming the morning before the procedure. For Heparin, depending on the risk of bleeding with the procedure and sort of the person doing the procedure, their preference, the heparin can be held anywhere from 30 minutes prior to about four hours prior to the procedure. On average we're holding it for an hour or two. And the same goes for our Gatraban and Bilalirudin. Our Gatraban is really similar to heparin in terms of its half life. Half life's actually a little shorter, so again, an hour or two is usually sufficient. And remember though that our Gadriban is primarily cleared by the liver. So folks with poor liver function, it's going to take them longer to clear. The half life can be as much as three and a half hours compared to about one hour with normal liver function. For bival rutin, that clearance is mostly dependent on renal function. But the half life again for a broad range of renal functions is somewhere between 30 and 60 minutes. So again, an hour or two is usually fine for holding bival.
- [07:37]
B
So that's all really important to think about here. But what about so called bridging anticoagulation? I know there are some patients who need as little interruption as possible of their anticoagulation and can be bridged off their longer acting anticoagulation with something like enoxaparin or even heparin. So Ronak, how do you select patients for bridging?
- [07:59]
A
So the moral of the story is the majority of patients will not need a bridge. And so this includes patients that have things like atrial fibrillation or atrial flutter, patients that have had venous thromboembolisms more than three months ago. And the evidence for this comes from the cardiology literature actually. So there was the bridge trial which enrolled 1900 patients on warfarin and they were on warfarin for atrial fibrillation. And they actually had exclus excluded patients with Recent clots, recent TIAs and mechanical valves. These patients were randomized to bridging with dalteparin versus placebo. And what they found was there was no difference in embolic events in 30 days after the procedure. So 0.3 versus 0.4% and a significant increase in secondary outcome of major bleeding, which was seen in 3.2% of patients who were bridged versus 1.3% of patients who weren't bridged. There was also the PERIOP2 study with just under 1500 patients with atrial fibrillation as well that were on warfarin. And what they were looking at was bridging back to a therapeutic INR after surgery. The important thing to note here is that this trial did include patients with mechanical valves and in fact, 21% of the patient population met this criteria. All of these patients were bridged off of anticoagulation prior to surgery with deltaparin. And then after the procedure, they were randomized to either dalteparin versus placebo in order to bridge back to an INR of greater than 2. And what they found was there was no difference in thromboembolism for either atrial fibrillation or mitral valve replacement groups. And also there was no difference for major bleeding between the two groups either. And we'll share some of the details of this study in our show notes. Note here that the history of warfarin skin necrosis is an absolute indication for bridging anticoagulation. And if you remember our prior discussion of patients with hereditary protein C deficiency, you'll recall why this is. People who do require bridging, however, are going to be the people that don't fit into the categories that I just mentioned. So, for instance, a patient that had a recent VT EL in the last three months, most of the time I'll ask if the procedure can wait until more than three months out from the procedure. And that's really because we're trying to minimize interruptions in order to get patients optimal anticoagulation in that supercritical window where they're high risk for propagation of clots and also new clots forming. But we do bridge if we have no other choice and the procedure is a little bit more urgent. I'll push harder to delay if within the first four to six weeks because again, this is the time where there's highest risk of progression and new thrombosis.
- [10:40]
B
And I think that that's, you know, really important. What Ronick just said there is that when you have a fresh clot, something that happened very, very recently, that early four to six week period, you're at very high risk for propagating the clot or developing a new thrombosis. So you, especially when you're thinking about a sur, which is a provoking risk factor for thrombosis. So you really want to set that patient up for success. And the data for the BRIDGE trial with atrial fibrillation is not going to apply to that patient who had just had a DVT. Right. Those are two different patient populations. And the PERIOP2 trial is another very good trial. But again, we don't advocate here. Even though they did include those with mechanical valves, we still tend to bridge them back to their warfarin. But it was a provocative study. Again, not powered to really find that definitive endpoint that we don't need to bridge bridge these patients after their procedure. So we often do that. But it is very interesting and something that we hope to see in the future. And so Ronick, as you were saying, we talked about the cases with you had a recent VT El. What about those who had like recurrent venous thromboembolisms or you know, what are some high risk cases that you'd really think about? Bridging?
- [11:47]
C
Yeah, again, you know, with like you said, recurrent VT El, the history of thrombosis during prior short duration holds of their anticoagulation. Those folks also deserve bridging. They've shown in the past their bodies, for whatever reason, are at high risk for forming a clot during a brief window off of blood thinners. So I do that this is not really evidence based just because these cases are a lot more rare. Folks with the highest risk predisposing conditions to VTE, I tend to bridge them as well. And this is stuff like antithrombin 3 deficiency, which we talked about in an earlier episode, is a very high risk condition, triple positive antiphospholipid syndrome, which we'll get into in our antiphospholipid episode. A very high risk group and then just really sort of special situations. I had a patient, for example, who developed extensive life threatening thrombosis of their entire mesentery vasculature in the postpartum setting. And unfortunately, this patient also needs estrogen containing oral contraceptives to control heavy menstrual bleeding that have required multiple transfusions in the past. And so we're kind of in this situation where she needs this blood thinner to protect her from clots while she's on this medication that is high risk for forming clots. There's no clinical trial here to tell us how to behave in this situation. So because her risk seems so great to me and given her history, I bridge her whenever she needs a procedure. These are sort of the situations run into Roanoke.
- [13:07]
B
What about specific cardiac indications? You know, we talked about afib. You don't necessarily have to bridge those patients. What are the specific cardiac indications where you would want to do that?
- [13:15]
A
In general, I advise patients that typically it's a Good idea to get their cardiologist to also weigh in here. And this is because they are on these treatments for a cardiac indication. And I think it's important for the person that is overseeing that care to weigh in. But really some of the examples include patients that have mechanical mitral or aortic valves. These are patients that you want to consider. Patients that had recent atrial fibrillation or atrial flutter associated embolic strokes that were excluded from the trials that looked at safety of holding anticoagulation without bridging. Patients that had recent PCIS on single antiplatelet therapy and anticoagulation. And really, really important to talk about these risk benefits. But in these situations I always involve the cardiology teams to help make the decision.
- [14:04]
B
I think that's really important. Again, we want to stress that because the Periopt 2 trial included mechanical valve patients, that doesn't mean we're recommending as a fellow on call that you don't need abridged them. It's a provocative finding. Was not powered for that. But it is really interesting that they included those patients. And it's something that you don't really think about. But it's really good to know there is some data out there for that. So how are you guys actually bridging these patients? You know, what do you do when you do need to bridge these patients?
- [14:29]
C
What are you using when I need to bridge? The biggest thing to emphasize, no matter what you're doing around your bridging plan, what agent you're bridging off of what you're using, you have to make sure you outline that plan in explicit detail. And we'll go over what I mean by that. But you don't want any room for error here. For most patients who need bridging, we use Enoxaparin or Lovenox, which can start after the second or third missed dose of their blood thinner. My personal practice is that for warfarin, I have them take their first Enoxaparin dose at the time they would have been due for their second missed dose of warfarin. And for doacs, I have them take their first Enoxaparin at the time they would be due for their third missed dose. As you probably just experienced, the language around bridging is very confusing. Things like take at the time you would have taken this or that dose. And we don't want confusion when it comes to blood thinners. So I actually have a smartphrase that I'll plug right into a My health message that gives exact dates and dosages to make sure there's no ambiguity. And we'll have a screenshot of what that smartphrase looks like in our show notes. But essentially I have at pre op day six, so like six days prior to the procedure, take your last dose of your blood thinner and in the example that I include in the show notes, it's warfarin. And then outline the next few days, including when they take their last pre procedural dose, which typically is 24 hours prior to the procedure and then the procedure and then the proceduralist will have to tell them when it's safe to resume. Usually it's about 24 hours after their procedure. In the case of our patient, after talking with his GI doctor, he does feel that it would be okay for that procedure to wait until the 12 weeks after his VT Eliagnosis, especially since that's only about two weeks later than it was originally planned for. We talk to the patient, we give him a plan to hold his DOAC for two days prior to the procedure with no need for bridging agents, and the GI doctors confirm that he can resume his anticoagulant with apixaban the following day.
- [16:28]
B
So in this case we were able to get away with no bridging anticoagulation. But how do you handle situations where bridging is needed that are a little bit more complicated? So we're going to throw this one to you. So let's say that we have patients who can't be given something like enoxaparin, Lovenox or who have had exceedingly high risk for recurrent VT El off their anticoagulation. So, you know, thinking about something like HIIT or something like that. So how do you approach some of these types of situations?
- [16:57]
A
This is tough and this is also really, really important. So although the majority of patients won't need bridging and those who do can largely be bridged with enoxaparin, there is a subset of patients who will require an alternative plan. And so as Vivek sort of alluded to, this includes patients with poor renal function where you can't use something like enoxaparin or perhaps the patient had something like hit where there is a contraindication to using heparin or low molecular weight heparin. So these patients will require a much more advanced level of coordination with the service performing the procedure, as they will probably require admission for anticoagulation infusion prior to the procedure. So for instance, for patients who have a history of VTE with even a short period of time off of anticoagulation. You can do the standard enoxaparin bridge and then admit for 24 hour heparin infusion prior to the procedure to shrink down the time off of anticoagulation as much as possible. And of course, that is in a situation where a patient's renal function allows them to be on enoxaparin in the outpatient setting and isn't somebody that has hit, for instance, in the past for patients with poor renal function or a hit history. You would want to admit these patients for the whole bridging period to anticoagulation with either heparin or for those with hit, a direct thrombin inhibitor like bivalrudin. Both the patient and the surgical services are likely to be very enthusiastic about this plan, of course, because this requires a long hospital stay where it feels like nothing's really happening. But it's necessary and you have to make your case to both parties that the goal that you're trying to achieve here is you're trying to limit the risk of recurrent thrombosis and bleeding. And you see that this is really the only way possible to achieve all of that.
- [18:44]
B
I can understand why this would catch patient and providers off guard. Think about having to recommend a five day admission for a screening colonoscopy. That's kind of insane. That's insanity. Right. But you just have to make sure everyone understands that this is about safety and minimizing risk. So you really have to understand the patient in front of you. It's not one size fits all. And think about the factors that Ronuk and Dan have discussed so far. So back to our patient. He does fine with his stent exchange. However, a few months later, you're on inpatient consults and you recognize the patient's name on your consult consult list. He has just come into the ED with a major GI bleed after being on an extended course of steroids for palliation of his bone pain related to his metastatic cancer. The ED wants to know how to reverse his blood thinner. So how are you guys handling the situation? A patient on apixaban eliquis, one of these Factor 10A inhibitors. How are you going to handle this situation? Reversing their anticoagulation?
- [19:40]
C
Yeah, this is tough, especially with the patient being on a Pixaban. There's a lot of great stuff about the DOAC medications, but one of the things is that for most of them we don't have an elegant way to reverse them. The first step in this case, besides providing appropriate resuscitation with fluid and blood transfusions, that sort of thing. And of course, discussing endoscopy with GI is to get an anti 10A level. We talked about this in earlier episodes. But before you proceed down a pathway of trying to reverse a blood thinner, you need to make sure that that blood thinner is still present, that there is something there to reverse. And so the name for this test is variable. Depending on what your system has, it might be called an unfractionated heparin level or a low molecular weight heparin level. They're all the same anti 10A test just calibrated to a different standard curve. In this case, we don't care about the absolute level. We just need to know, is there something there in the bloodstream inhibiting factor xa or is there not something in there? So if the level comes back undetectable, there's no role to attempt reversing because there's nothing there to reverse. For patients on dabigatran, which, remember, is a thrombin inhibitor, some labs may have a modified thrombin time assay they can run to try and detect the presence of such an inhibitor. But it's important to know that For Dabigatran, the anti 10A level is meaningless. If the test does come back suggestive of a drug still in circulation, then we can start our efforts to try and reverse it. For dabigatran, we have a monoclonal antibody specific to the drug called iteracizumab. Praxbind is the brand name for that. And it kind of can soak up the drug in circulation like an antibody does and reverse its effect. But depending on where you practice, this may or may not be immediately available. For the 10A inhibitors, there technically is an approved reversal agent called andexanet Alpha or indexa. But practically speaking, there may as well not be one. This medication is not even readily available at many tertiary care centers. It functions as a dummy protein of factor 10a. And so it competitively inhibits the effects of the DOACs. But that also means it requires continuous readministration to maintain its reversal effect. In practice, for a life threatening bleed and a patient on a doac, we tend to give a prothrombin complex concentrate. It's basically a concentrated combination of the factors depleted by warfarin. The idea being that we're trying to overwhelm the effect of that DOAC medication by providing the body excess clotting factors. At Rouleau University, we use a fixed dosing protocol for this. Your center likely has its own protocol based on whatever PCC product, whatever prothrombin complex product is on formulary. There is a new medication in the pipeline called Serum Parentag and great name. I know it has shown promise as a more viable reversal agent, but it's still in early phase trials. It doesn't look like it's coming anytime soon, unfortunately. But hopefully someday in the future we'll have that at our disposal.
- [22:32]
A
You know, it's really interesting, Dan, that you bring up the whole conversation about andexxa and about its availability, et cetera. If I recall, when this drug first came to market, you know, a lot of people were really excited about it, but there's also a lot of speculation about how effective it really was. Vivek, you look like you're about to jump out of your seat. Looks like you want to say something. I assume it's to comment on this.
- [22:57]
B
Tr.
- [22:58]
A
What's going through your mind right now?
- [23:00]
B
Yeah, so I think this is really important to understand the data behind these things. So there's two pivotal studies looking at this drug. One was called Annexa 4, and that was a single arm study, included over 100 patients at multiple centers. And the idea was that basically, is this drug effective? And in that study, what we found was the patients who got this andexanet alpha medication that Dan described, a bolus followed by a continuous infusion. We knew that, yes, that we were able to normalize the activity of their factor 10a and that it did achieve good hemostatic efficacy. The problem was, once you gave this drug, you also had a pro coagulant phase. So there's also an increased risk of thrombosis with this drug as part of it. And the other thing is, you have to keep on, as Dan alluded to, you have to have this continuous infusion. It's very costly. You have to keep giving the drug, drug somewhat continuously. And the proponents of the drug say it's great, we have a direct way to fix this. But the other people about this were saying, well, what if we just use the traditional old pcc? What if we use that? And so that's another way that we can reverse anticoagulation. And that led to a recent study published in the New England Journal of Medicine that was a randomized control trial, randomized one to one, called Annexa I, where patients with an intracranial hemorrhage, Annexa I for intracranial hemorrhage were randomized to indexonet alpha or usual care, whether that was PCC or something Else, what's really important to know is that 15% of patients in a usual care arm did not get pcc, which is the de facto standard of care as a potential reversal agent for those who are on doac. So that's one nick against this trial. The other thing that we found in this study is that what was the primary endpoint here, and it was a very interesting composite endpoint really of hematoma volume expansion. And when you looked at that, actually there was really good control of the hematoma expansion with the Adnexanet arm at 76% of patients compared to 64% of patients. Also, the important thing to know as the annexa arm had a higher rate of a thrombotic event, we're talking 10% versus 5%, and that included arterial events. We're talking about strokes and mis. I mean, these are really serious events. That's how pro coagulant the patient's system is. When they get indexin at alpha, you're getting double the rates of thrombotic events. And the ischemic stroke. Stroke rate for the indexonet Alpha group was 6.5% versus 1.5%. So you're clearly seeing this is being driven by an increased rate of things like ischemic stroke. When you give something like the indexin at alpha. When you think about it, okay, well, hematoma volume expansion is better, so that's the most important thing. Right. But when you looked at actual clinical patient outcomes, you know, are they actually better off six months down the line? We didn't really see that major benefit. So we still don't know to this day if. And dexanet alpha is better, because although it's good at controlling hematoma expansion, that didn't correlate to a real meaningful clinical endpoint. When we think about survival and we think about patient reported outcomes, what it did do that we know for sure is it has a safety signal with double the rate of thrombosis. So that's why it's not clear cut whether you should use the drug. It's also quite expensive, which is why not all centers have it on their formulary. But that's my little aside there. After that soapbox, let's get back on track. And have me stop ranting, because I could go a long time about how that composite endpoint was chosen, but that's for another day on a fellow on call journal club. So, Rona, can you tell us a little about how you reverse other anticoagulants? What are some other reversal agents out there. And can you tell us a little bit more about this PCC thing that I alluded to?
- [26:36]
A
Absolutely. So the one drug that we often think about that's easily reversible is warfarin. And that's because our listeners know that the way that warfarin works is by antagonizing the action of vitamin K, and therefore it suppresses the production of factors 2, 7, 9, and 10 along with protein CNS. And since this medication is not a direct factor inhibitor, unlike the doacs, all you really have to do to reverse warfarin is replace the missing factors. We can do this in a couple of ways. So, number one, you can give patients vitamin K to allow their liver to resume normal levels of production. We can also give something called prothrombin complex concentrate, or pcc, and that contains all the factors that warfarin depletes. And this allows for rapid reversal of the anticoagulant effect without the volume that would be required for plasma infusions to achieve the same degree of reversal. And if these aren't available at your center or they're contraindicated, because many of these products contain heparin, so patients with a history of HIT should not be exposed to them, then you can use things like plasma and vitamin K in combination as well. Protocols for reversal are really guided by the inr. So an INR upfront to help plan reversal is really important here. And this is because, again, we're talking about warfarin in this situation. This is analogous to how we were using drug levels like Dan had mentioned with the DOAC scenario just mentioned moments ago. The heparins, which include both unfractionated heparin and low molecular weight heparin, these can be reversed by an agent called protamine. However, this can be a little bit tricky, and it's a little less effective for low molecular weight heparin than for unfractionated heparin. But for all intents and purposes, protamine is what you're reaching for when you're trying to reverse a heparin. H. Fonda paradox is much more like a DOAC in that it's not adequately reversed with protamine. So we often use the same strategies as we discussed in the DOAC section, which pretty much means using things like PCC in order to try to overcome those effects.
- [28:39]
C
Yeah, and I'm glad you mentioned protamine. This is one of those things that you occasionally do have to reach for it, and it's always something that gives me anxiety. The reason for this and the reason that we said it was tricky is because although protamine is a really good reversal agent for unfractionated heparin, the way you have to calculate how much protamine to give is a little bit involved. You don't want to overshoot your target range with protamine because at higher doses it can actually cause hemodynamic instability. It causes this sort of vasoplegia with a big infusion of it. And it also eventually has an anticoagulant effect if you overshoot by too much, so making a situation that was already bad even worse. I also have a smartphrase for this, and we can include that just because it kind of outlines the math in our show notes. But essentially what you need to do is you use the infusion rate of the person's heparin and you use that to calculate how much heparin is likely to be in their body, including a factor that takes into account the time between the administration of protamine and the stopping of the heparin infusion to kind of calculate how much has probably been metabolized off. And then you use that to dose your proteamine. We'll have that math all outlined in the show notes. It's a little bit different for enoxaparin. There's a fixed dosing protocol with two doses based on how long ago the last enoxaparin shot was given. But it's a lot more straightforward in terms of the math. And so we'll have that dosing in our genotes as well. But protamine, it is out there. It's not as easy as just turning it off like you can give PCC with warfarin. So to wrap up our case, this patient's low molecular weight heparin level did come back detectable as greater than 1.5. So consistent with adherence to apixaban. And we give him a dose of four factor PCC for his life threatening GI bleed. He also gets red cell transfusion. His Melanie sort of slows down over the next 24 hours. And an endoscopy shows a large ulcer in the stomach with a bleeding vessel at the base. GI is able to place a clip there. And after discussion between his family and the oncology service, the patient elects to go home with hospice care and will not be restarting a Pixaban. So this patient, we were able to at least fix the bleeding. Obviously, there were greater things going on in his health that required a different orientation in his care. At the end of the day, but certainly glad that we were able to help out with the problems that we could fix.
- [30:58]
B
Yeah, I think this is a great case that outlined the important points. And remember everybody, if you want to know if somebody was taking that doac, just get that heparin level or low molecular heparinoid assay, whatever you want to call it. It's just a different nomogram. Get that anti 10A level. That's what the drug is. It's an anti 10A drug. So if it's positive, you know, it's in the system. So if you're trying to binary is it in there or isn't, that's your answer for that question. Remember from the nuances that we talked about about this reversal agent of adnexin at alpha, it increases your risk of thrombosis. And that's pretty, that's so, so important. We can't emphasize that enough and the cost implications associated with that. PCC does the same thing. So if you have a patient on warfarin, you don't want to just be throwing PCC at them. Right? In that study there was still a 5% rate of thrombosis. So keep that in mind that you don't just give PCC willy nilly to patients, even if they're on warfarin. We're talking about major bleeding events where we need to reverse this anticoagulation.
- [31:52]
C
That's a really great point. We don't just reverse anticoagulation because someone nicks themselves shaving and it's bleeding for a long period of time. This has to be life threatening in order for us to take the measures because they're on blood thinners for a reason. And we shouldn't take lightly the decision to immediately counteract the effect of that. And you know, we covered a lot of ground today. But basically, when it comes to planning a procedure, the moral of the story is you need time to make sure that all of the relevant parties are on board with your plan and that the plan is very clear and leaves no room for ambiguity. You got to involve the patient, you got to involve the service doing the procedure and anesthesia to make sure that everyone knows the deal. There are some trials out there that looked at the need for a bridging anticoagulant agent versus just stopping a blood thinner for a period of time prior to a surgery. For folks with really low risk indications for anticoagulation like atrial fibrillation without a mechanical valve or people with a VTE history but Their most recent clot was not within the past three months. Those folks probably don't need a bridge of any kind. For folks that do need bridging, we usually use an oxaparent. And in special situations, we may even have someone admitted for an extended heparin infusion, depending on what their particular situation requires. And then, as we talked about, different agents need different strategies for reversal. It can be tricky with the doacs because for the time being, we don't have a great specific agent to reverse most of them, with the exception of dabigatran and Iteracizumab. And then lastly, when it comes to reversing heparin, there's a lot of math involved. Make yourself a smartphrase. We'll have the math in our show notes. Anything else I left out? Any other points you guys wanted to drive home? Home.
- [33:37]
A
I thought that was a fantastic recap between the two of you. And my only reminder to our listeners is to make sure you check out our show notes. There's a lot of important information, both practically speaking, but also sometimes reversal agents questions do show up on your exam. So if you don't ever find yourself doing hematology, at least for exam purposes, this, this is very, very testable. So I think that wraps up another fantastic episode of the fellow on call. So until next time, we'll see you all later.
- [34:04]
B
Later. See you later.
- [34:06]
C
Peace.