SCCM Resource Library-When Guidelines Don't Help: Challenging Cases in Hematologic Management of Mechanical Support Devices

When Guidelines Don't Help: Challenging Cases in Hematologic Management of Mechanical Support Devices

Video Transcription

Good morning, everyone. My name is Marie Steiner, and on behalf of the presenters of this session, we would like  to thank the organization's SCCM for inviting us to present this virtual panel discussion,  Guidelines Don't Help, Challenging Cases in Hematologic Management of Mechanical Support Devices.  As mentioned, I'm Marie Steiner. I'm a professor of pediatric critical care and hematology at the University of Minnesota in Minneapolis. And I'm William Daiger. I'm a pharmacist  specialist at the University of California, Davis system. I hold several clinical professor  positions and work a lot with anticoagulation issue in both pediatric and adult ECMO patients.  Hello, everyone. I'm Mark Cipolle. I'm the chief of the division of trauma and acute care surgery  at Lehigh Valley Health Network. I've had the opportunity to operate on patients on ECMO, both at the bedside and the operating room. And welcome, and thanks for listening.  And I'm Subhashish Chatterjee. I'm a cardiovascular surgeon, as well as a critical care intensivist and the ECMO director at Baylor St. Luke's in Houston, Texas.  None of the faculty here today have any disclosures relevant to this presentation,  but we are going to be discussing off-label use of anticoagulants, coagulation factor concentrates, and antifibroanalytics throughout the discussion.  Our format is going to include initially a venal venous ECMO case presentation  with comments and discussion from our panel. We'll then move on to a venal arterial ECMO case presentations, again, with comments and discussions from the panel. And finally,  we'll wind up with questions that are submitted during the presentation directed to the members of the panel.  So we're going to start out with our first case. This is a patient who has been admitted with  COVID-19. He has received remdesivir, convalescent plasma, dexamethasone, and high flow oxygenation  for three days. But he does develop progressive respiratory distress, hypoxia, and inability to maintain blood gases, and so is placed on bifemoral venal venous ECMO.  So when we have patients on mechanical devices, there's multiple reasons we need to think about  anticoagulation therapy, because these are non-endothelial surfaces. Their unique nature makes them more prone to clotting in some cases. There's shear stresses that we might face,  as well as hemodilution that can occur in these patients. So it's common to anticoagulate these  patients, but we're dealing with a lot of factors and a lot of issues. And just as we see in our  case, it's not only the circuit we may have to anticoagulate, but it's also the patient that goes with it. We're also cognizant of other challenges we face, because there could be  bleeding from surgical sites or the cannula in certain sites. We have to be cautious about other  major bleeding, including intracranial hemorrhages. The cannulas can clot, the oxygenator can form  clot, the patient themselves can form clot, and also we're dealing with things like thrombocytopenia  that can be the result of the circuit. So there's a lot of things we have to balance as we move  forward, and this is part of what we're going to try to present to you today, really dealing with patients that are challenging and maybe not really described in the guidelines.  So this exactly, as Bill alludes to, is really one of the challenges when it comes to  anticoagulation with respect to ECMO. The major international authority on ECMO is the  Extracorporeal Life Support Organization, or ELSO. And when you look with respect to its guidelines,  whether in adult respiratory failure or any other aspect for which ECLS is used, there's very little  specific guidance in terms of how to manage anticoagulation. It is a balance of patient  and circuit and clinical factors. So generally the most common anticoagulant we'll use is heparin.  However, some centers have now moved to using a direct thrombin inhibitor as their first-line  agent. We have variable approaches in how we want to assess or measure the effects of these agents,  and we'll describe this in a little bit more detail later on. The two direct thrombin inhibitors  available in the United States are gatchaban and bivalrudin. Here, again, the APTT is a primarily  used assay because the antitinA, which can be used for heparin, cannot respond to direct thrombin  inhibitors. And depending on the situation, such as in the operating room, the activated clotting  time may be used as well. But we're also faced with a couple unique situations, such as heparin-induced  thrombocytopenia, or antithrombin deficiency, which we will also discuss a little bit later.  Interesting enough, there's actually some data, especially with the VV ECMO  situation of actually doing no anticoagulation at all, and Subha is going to mention a little bit  more on that issue. So one of the challenges in all ECMO is managing the bleeding risk versus the  thrombosis risk, both to the patient because of having large borcanulas and to the circuit.  So with respect to this, this is an interesting survey that was done by the Toronto group with  respect to multiple centers across Canada, surveying what exactly people did with respect to  anticoagulation rate. And you can see that, in general, patients had a much higher rate of  thrombosis, 53% compared to bleeding rates. And interestingly, in general, in the literature, the  mortality is higher with thrombosis rather than bleeding, sorry, with bleeding complications  rather than thrombosis, especially circuit thrombosis. An interesting sub-analysis within  this group is they looked at the centers that ran the PTT level at a higher intensity versus a lower  intensity. So the lower intensity group had about a less than 10% bleeding rate with, however,  about a third of the patients had a thrombosis event, whereas the high intensity group had over  half the patients have a bleeding complication with under 10% thrombosis rate. So this is sort  of what the surveys were in terms of people in actual practice. With respect to respiratory  failure, the major landmark randomized trial that was done most recently is the EOLIA trial, multi-center international trial with looking at ECMO for ARDS. Again, this is in a  non-COVID setting a couple years ago. And the trial protocol had a PTT level stipulated at  between 40 to 55 seconds or an anti-10A activity level between 0.2 and 0.3. And you'll see here,  even with this, the bleeding needing a transfusion rate was about 46%, which was clearly higher in  the ECMO group compared to the control group. But the risk of massive bleeding was very low, a 2%  rate in the massive bleeding rate. So that was sort of considered, I think I would say, probably  standard of care now with respect to ECMO anticoagulation intensity. You will note that in  the EOLIA cases, about a quarter of the patient actually had circuit changes and about a one in  six patient had some level of circuit thrombosis. So in general, they tended to err on the side of  avoiding bleeding and taking the risk with respect to circuit thrombosis.  So in our experience here in Houston, when we started with COVID ECMO, so we typically run our  respiratory failure VV ECMOs with a PTT level between 40 to 55. We'll talk a little bit about  other strategies. We use a combination of thromboelastography and taking a look at anti-10A  to try to make sure that they're sort of all in concordance. But we tend to run our VV ECMO cases  a little bit on the lower side with our VA cases a little bit on the higher side. When COVID-19  first came out, there were multiple reports of thrombosis. We saw multiple instances of CRT  circuits clotting off. So we were certainly nervous of wanting to avoid thrombosis and running these patients at a higher intensity level. On the other hand, back in the spring of  2020, we were also afraid of endobronchial bleeding and having all sorts of bronchoscopies  and aerosolizing procedures and being exposed more often. So we decided that we were going to run our  PTT level a little bit higher than normal because of the thrombosis risk. So we tended to run the  PTT somewhere between 60 to 80. I can tell you from our own experience, we've done over 40 COVID  ECMOs, probably closer to 45 now. We've rarely seen circuit changes. I would say probably  maybe five or six circuit changes with a typical duration of somewhere between 23 to 25 days is our median length of time on circuit. We've had a couple patients who've  gone over 40 days. But in general, thrombosis events have been rare. We've had two patients have head bleeds, a couple of other like nuisance-related bleedings, and by that I mean  sort of post-tracheotomy or oropharyngeal bleeding. But in general, in those settings, we've been  pretty conservative. We tend to stop our anticoagulation for 24 to 72 hours as long as our flows are doing well. So anybody else with respect to kind of how you ran the COVID ECMOs?  Bill, any comments in terms of what you've seen in terms of whether people were a little bit different in the COVID setting compared to others? Yeah, I have had some experience  dealing with our COVID on ECMO patients, and sometimes we're really trying to balance the  bleeding and thrombosis risks, as you mentioned here, knowing that COVID adds another hypercoagulable  condition into the picture. We really don't have a clear idea what the optimal ideal sweet spot is,  and it might depend on other factors such as the D-dimers and any sort of signs of clotting, or a concern about a bleeding event versus a pulmonary embolism that might drive  physicians or clinicians on how to set target goals that may have to change on a daily basis.  And I'll talk more later about these ranges and what might be different between institutions.  So Bill mentioned, I think, very interestingly, you know, what do you do with respect to, you know, can you run VV ECMO off of anticoagulation? This was a systematic review  looking at a number of reports, actually two in the VV ECMO circuit, four with VA anticoagulation,  and you can see here they had about 70 patients. The majority of them were post-cardiotomy,  about two-thirds were after heart surgery, but you can see here that, by and large, they did  pretty well. This group had about a 70% overall survival, and on average this was about a median  of about 45 hours, about two days or so, and they did see a reasonable number of circuit complications.  Again, what I would say with respect to anticoagulation, and this is what we really learned from EOLIA, we sort of managed it, is you can get away with lower level anticoagulation  that you think you can, as long as you're flowing well, as long as you're flowing, you know, four to  five liters, and you have good communication with the perfusion. I mean, this really underscores the multidisciplinary aspect of ECMO care, but if your circuit's okay  and you're talking to your perfusionist, you can get away with holding anticoagulation for extended periods of time, you know, safely as needed.  What are some of these complications that we have to deal with in terms of clinically  significant bleeding? Well, pulmonary hemorrhage, used as a generic term, is one of the ones that's  sometimes very difficult to manage. Lots of things can cause pulmonary hemorrhage, diffuse alveolar hemorrhage in the strict sense, focal trauma or injury, left atrial hypertension,  coagulopathy or anticoagulation can cause pulmonary hemorrhage, and then there are a lot of  different things that we can try to attempt to diminish pulmonary bleeding, which includes  potentially reducing or stopping anticoagulation, which we just talked about being feasible to do on  ECMO, enhancing systemic hemostasis, sometimes you're behind on your platelets or your fibrinogen,  but sometimes you have to revert to actual local control via bronchoscopic techniques or interventional radiology techniques or using hemostatic agents in a local fashion.  There is surprisingly little data on pulmonary bleeding on ECMO. There's more data available in  the literature in other scenarios that we'll talk about here because I have found that they've  been helpful and effective. Bill's going to talk about systemic administration of additional  hemostatic adjuncts later, but recombinant factor 7A, epsilon-aminocoproic acid, or AMACAR  trade name, or tranexamic acid, have been used for severe pulmonary hemorrhage, some on ECMO,  some not on ECMO. The bone marrow transplant population, hematopoietic stem cell transplant population has had a lot of dealings with pulmonary hemorrhage and has helped inform  administration of these agents. In the last 15 years or so, people have used some of these agents  via bronchoalveolar lavage or direct installation, just lavaging the endotracheal tube to stop  pulmonary hemorrhage, not necessarily knowing where it is if you're doing it blindly, but if you're  putting a bronchoscope down, you can direct recombinant 7A or tranexamic acid, usually in  non-ECMO settings is where this has been described. You see the doses there, and it has been found to  work quite effectively, and of course, the case reports and small series that are published.  We don't really know what the non-successful denominator is, but I used it and have found it very effective on ECMO, in VADs, and in other settings. It's also feasible to aerosolize  these antifibrinolytic agents. There's a significant amount of work that's been done in the stem cell population. There's a recent review article by Fan and colleagues that's in  Frontiers in Pediatrics that just came out a couple months ago, doing a nice review of recombinant factor 7A and tranexamic acid as aerosols for pulmonary hemorrhage in a  different variety of doses and schedules, but certainly effective in a lot of people's  experience. The concerns about doing this in someone with COVID, obviously, are the aerosolized particles, exposure to the virus, but there are also ways as the direct installation  method to do this. Now, bear in mind optimal criteria and optimal dosing and the adverse  risks for doing these things are not clearly established. There is literature that talks about  the lavage and the aerosolized routes being not particularly complicated to do and with  very minimal complications. I will caution folks that I have directly instilled recombinant 7A into an endotracheal tube and blocked the tube with the plug that developed.  So I think these are things that need study and are Hail Marys when you can't control your  bleeding any other way and you need to control it. But gentlemen, other thoughts, other ideas.  Maria, I thought this was really interesting and since I deal only with adults, I thought these  are real novel solutions. When we first started, we were very afraid of bronchoscopy in the  COVID setting because as an aerosolizing procedure, the thought was try to avoid bronchoscopy almost  at all costs just to reduce the exposure risk. Over time, and I think now as people are getting,  as providers are getting vaccinated and we've had more experience and more PAPR experience,  we have sort of, we're treating it more like we used to in terms of the standard VV ECMO. But I think some of these novel agents are indeed really eye opening.  And I just add, if you're going to think about doing these novel therapies in your institution  and you have not yet established it, it's important to think about it in advance because  from the pharmacist's perspective, getting the order set put together, at least how it works  in your EMR, understanding what's going on so everybody's on the same page. So when you do  want to do it, it's not trying to climb a big hill. It's rather a more simple, easier process  to do and everybody knows what their role is and how to do it, what kind of devices need to be used  for installation and such. Yep. Another set of complications that we run into, not infrequently,  are gastrointestinal hemorrhages. The etiologies you see listed to the left of the slide, gastritis  or ulcers. Coagulopathies, including acquired von Willebrand's disease, which occurs on ECMO circuits as well as in ventricular assist devices. Infections, ischemia and infarction.  Management, again, as Shuba said, you can certainly reduce and stop your anticoagulation,  especially on VV ECMO if you need to. There are means of local control, endoscopy, or again,  your friendly interventional radiologists. Surgical control is sometimes necessary. Of course,  you've got an infection, you've got to treat that. But there is some role potentially if you have  an acquired von Willebrand profile in the opportunity to provide some factor replacements,  maybe not necessarily the HUM8P concentrates, but you can give platelets, you can give cryoprecipitate.  The story's not completely known as to whether or not those work in this situation, but again, you've got significant hemorrhage, you've got to deal with it and try and control it.  Other thoughts, gentlemen?  No. It's just sometimes, I guess, the gastrointestinal hemorrhage, depending on the severities, sometimes you have a little bit more time to deal with it versus an  intracranial hemorrhage where you have to kind of jump on things a little bit faster.  Yeah. I would say that for GI hemorrhage, which we're called about as a surgeon to be on board, we're usually the third line. You've got endoscopic control, interventional radiology  control, but as I'll talk about in my section, if you have to open up someone's duodenum and ligate a bleeding ulcer, you can do that at the IC bedside if necessary.  You're probably not going to do vagotomy, but you could do that.  Yeah.  And then we also should talk about the stroke and the central nervous system hemorrhage, which are probably some of the most challenging and most devastating complications we face.  The etiologies can be multiple. They can be the initial traumatic injury or from hypoxia, ischemia, thromboembolic hemorrhagic. It's surprising to me, and I've got ECMO since  it was originally starting. We really don't have a lot more guidance in terms of what to do with these catastrophic or near catastrophic central nervous system events.  And we've been doing ECMO a long time now.  We generally do reduce and stop the, or stop the anticoagulation. I'm surprised at how many times we have to rethink and reinvigorate the attention pain  to the basics of central nervous system resuscitation. If you can get the head of the bed up, get the head of the bed up. If you can get your sodium up, get your sodium up.  If you can get your temperature down, get it down. The normal things that we're gonna help preserve neurons. But then, you know, sometimes it's devastating enough  that we need to consider decannulation. Whether we have to come off ECMO because we can't control the brain bleeding any better on circuits, we better come off.  Or if it's catastrophic enough, do we need to decannulate because there's nothing more we can do?  If you have a window for involving your neurosurgeons, is there anything the neurosurgeons can do? And if they do need to do something, are you able to provide them  with a safe hemostatic environment, whatever that is, because that's not clearly established. And then is there a role of anti-fibroanalytics  in a localized stroke and maybe it's recoverable?  Your interventional neurology or your stroke team is potentially also a team of valuable allies  to incorporate into the management. But all of this needs to be sort of proactively thought about risks, benefits, family wishes, the infectious situation,  the long-term trajectory of the patient. And surprisingly, we really don't have good guidelines for what to do.  And if we get someone to recover, where do we go after they have stabilized from their events? Do we re-anticoagulate them? Do we operate on them? It's still very much a black box  in terms of what we do when someone has catastrophic CNS events.  Maria, I think that's an excellent summary of, this is a really difficult problem. I think this is probably, in many ways, this is the most devastating complication of ECMO.  I think that the, and it's really on an individualized basis and it really requires a multidisciplinary approach to it with family, with neurologists,  and with the other members of the team. I will say that with regards to a couple of situations. So, when we started our COVID experience in the spring to summer of 2020,  we initially had about a 75% survival in our ECMO group, really good results. And I would say over the last three to four months, our survival, and there are multiple reasons,  I think our survival now with ECMO is probably on the order of 20 to 25%. And I think it's because we're seeing patients later on,  I think we're getting better at avoiding intubation in patients and some of the other interventions. So, the patients that we're seeing now,  I think are sicker or have more lung damage than they did much earlier in the pandemic.  And I think that's giving us a little bit of pause with respect to more realistic assessments with our families. I mean, we make sure that once a week we have a multidisciplinary,  the families are updated daily, but we have a once a week Zoom meeting with all the families and all the providers and palliative care to discuss sort of what our goals  of recovery would be. And one of the things that really prevents moving forward,  both from recovery or even eligibility for potential lung transplant, is a major complication. And we would consider like a CNS bleed.  Again, you have to look at how big of a bleed is it, what the implications are for it, but that's a pretty significant setback. And I think if we flip over to VA ECMO,  in eCPR cases, when we see a head bleed, that's a pretty significant complication in terms of that. I think we're a little bit more aggressive in other aspects,  but I think the key thing to emphasize is this is multidisciplinary. You need the neurologists and neurosurgeons involved because they're looking at things in a different way  and can give you some better prognosis. And obviously the key to this is stopping anticoagulation. So any other thoughts on the head bleed situation?  Just sometimes we may be faced with reversing the anticoagulation or actually whether it's an embolic stroke, we might be looking at thrombolytic drugs.  So it's important to get all the players involved sooner than later so there's no delays because time is of the essence, especially if it's an embolic event.  Yep.  Very challenging. Lots of room for more work. Right. And so this brings up, you know, as we're talking about this, you know, well, how about anticoagulation  after you come off of ECMO? And so I think this is a sort of underappreciated aspect. So this is analysis in the non-COVID situation. So this is the Maryland group.  They looked at 48 patients who all had been successfully decannulated after VV-ECMO  and they did routine surveillance. And what they found was that 85% of patients had evidence of DVT with about three quarters of them  having an IJ clot and about 60% having a femoral clot.  Interestingly, there were no PE cases. And when they looked at it, they didn't find a relationship between the intensity of anticoagulation, the time that they were therapeutic  or the time on ECMO. So is our practice, we saw this study a couple of years ago. We actually made it a point, again, this is prior to COVID, of routinely getting surveillance DVTs.  Besides, you know, everybody was on standard DVT prophylaxis but we would get surveillance Doppler studies to determine who needed perhaps longer term anticoagulation.  And I think this really set up with respect to COVID, you know, everybody's familiar with the hypercoagulability of COVID.  Patients tend to come in as soon as they're in the hospital. We have them on systemic anticoagulation. So by the time they come to ECMO, they're already anticoagulated.  So even after decannulation, they're still anticoagulated. But this, I think, was an interesting report out of Marseille, France. Only 13 patients, but they had 100% incidence  when they looked by CT scan in COVID patients with evidence of DVT. And this is despite the fact that for the most part, patients were anticoagulated appropriately,  perhaps a little bit on the lower end of intensity, but they were anticoagulated appropriately. So I think it is reasonable to continue anticoagulation.  After decannulation, what we do in our practice is we will also do surveillance Dopplers in some of these patients. And on two occasions, we've given,  we put in IVC filters for patients who had evidence of large DVTs post-ECMO decannulation, despite being anticoagulated.  Any other comments on anticoagulation after decannulation?  I think the thing I'll throw in is that in general for us, we anticoagulate all COVID patients unless there's a reason not to. So they'll continue on.  It may mean a different level of anticoagulation as there's some recent literature that's kind of expressed some concern about treatment doses in patients.  Even in the ICU, obviously ECMO is a different scenario, but we have to be cognizant of bleeding issues as well as the risks, especially the D-dimers are still elevated.  So in general, I think most of us would still sustain some level of anticoagulation until the point of discharge or reason not to. Also, I would like to comment on the,  just in the screening, also make sure you check it out with your facilities because the more screening you do, so there's actually a report about the incidence of DVT  in COVID patients in the ICU. And it's listed at 69% in a facility that did a lot of screening. So depending on the reports, obviously screening brings up more cases,  but also you're benchmarked about having events. So make sure you clear that and watch how you report your data.  Great.  Okay. So Mark, if we need procedures while a patient's on ECMO,  what sorts of considerations have to be put into place?  Yeah, I think that we could do more at the bedside  than you think. I'm sitting here thinking about what I can,  it's not ideal, but certainly we can. Just the other night, a couple of call nights ago, I operated on a woman who had two doses of TPA for,  after a cardiac arrest due to pulmonary embolism, she had a liver injury, excuse me,  two liver injuries from the Lucas device and five liters of blood in her abdomen. So we had our surgical team, the perfusionist and everyone at the bedside,  and we were able to do two hepatographies, et cetera, et cetera, apply topical hemostatic. So there's lots of things we can do at the bedside. Certainly, and this lady, by the way,  it was on VA ECMO later that day.  I think that holding anticoagulation as we've started to talk about here,  we never hold prophylactic doses of anticoagulation, but the patients that we're talking about are gonna have a PTT in the range of 40 to 80, as Subha had mentioned.  And that's where it's key for the surgeons and the ECMO folks to get together and say,  how long do we need to hold the anticoagulation? Obviously, we'd like to have it held as long as is reasonably possible, but it's not a game changer.  I personally have done more than one operation on full anticoagulation.  It's not desirable, but certainly it can be done because if we get into surgical bleeding, we'll stop it with suturing or topical hemostatics, et cetera.  So that's basically, I call it a negotiation.  Hey, we're having lots of trouble with this circuit. Can we only hold the heparin for a few hours? Fine. Or this guy's been doing fine.  We could hold the heparin for maybe an entire day if they need a procedure. So that's where, as Bill alluded to,  communication is important. And we are going to anticipate our bleeding issues. We know that we have rebound effects from these anticoagulants, even if they're held.  For instance, if we don't see any untoward bleeding when we're doing a tracheostomy, which is our most common procedure in these patients,  we're gonna pack the wound with hemostatics because we know that that patient's gonna go back  on anticoagulation relatively soon. And so it's like, we're acute care surgeons. As a trauma surgeon, we deal with this balance between bleeding and thromboembolism constantly.  Every day, we have two or three patients that come in with a head bleed on anticoagulation. So we do this constantly, balancing the risk of bleeding, and we're a lot better at it.  I can say that both trauma surgeons and neurosurgeons have gotten more comfortable with re-anticoagulation,  COVID and ECMO aside, over the last few years. And that's important to know. Don't assume that the surgeons are gonna run away  and be risk-averse because the patient's anticoagulated and they need to go quickly back onto their anticoagulation. We're used to it. We deal with it constantly as trauma surgeons.  We understand it.  I'll tell you one thing that COVID's taught us is that maybe we don't always have to operate. Maybe we can get you through without an operation  with your appendicitis or your cholecystitis and certainly diverticulitis, which we've been doing for a long time now.  But of course, we need to be called early and make those decisions with the primary team. Interventional radiology may be helpful, but of course that means a road trip.  As all of you know, CT scanning and IR have revolutionized how we take care of solid organ injuries. And they may have an important role to play here.  So I would say that don't call your surgeons early. You'd be pretty amazed at what we can do at the bedside and we don't have to make that road trip.  And just, I'd like to make a couple of comments about tracheostomy, because it's going to be the common or most common or one of the most common procedures we do on these patients.  You know, as Subha alluded to, when this first started, we, you know, oh, we're not going to trach these patients. Or if we are going to trach them,  we're taking early tracheostomy off the table. We're going to be doing it day 21 to 28. And then we found out that we're jamming up our ICUs  because we're waiting so long to do the trachs, et cetera, et cetera. So we've come full circle in our group. And I think Subha may be saying the same thing.  It's, I love this line that was by Dr. McGrath  in the British Journal of Anesthesiology. He says, tracheostomy is just basically business as usual with better PPE. And that's basically where we're at.  So if you look at the literature now,  it's basically day 10 to day 20, patients are getting their tracheostomies. You know, Mark, I would say with respect to tracheostomy, I 100% agree.  We started out, we were going 21 days and then, you know, trach at that point. I think there is some experiences that are out there that, you know, if you look at the NYU group,  they basically trach patients within 48 hours of putting them on ECMO. But I, and we've sort of leaned towards a little bit more aggressive posture only because, you know,  now that potentially transplant is an option for some, the sooner we can cut down on the sedation and like, you know, while they're on ECMO and get them awake and alert  and making some rehab progress, they become a more viable candidate. And that's really facilitated with tracheostomy.  So we're now probably more in that 10 to 14 day range, sometimes even within seven days of tracheostomy. I could tell you more than once, we've referred a trauma patient  or a sick general surgical patient to our ECMO colleagues and they call us two days later, when are you doing the trach? Like, wait a minute, we just, okay. Exactly.  It's kind of like a deal, you know? Right. And I think it's also important to remember, I mean, you know, we are seeing, you know,  I think there are nursing shortages that are out there. And so there are the ECMO capacity of centers is I think in some ways it's more challenged today  than it was six months ago or nine months ago. And so you have to be very wise about who you're putting on ECMO and who are the patients who are gonna be,  you know, viable candidates because this is not like after post-cardiotomy where they're gonna be on ECMO for three to four days. These are people who are gonna be on ECMO  for three to four weeks, typically at least, you know, and you have to think about that, so. Yeah, yeah. Good points. Yeah, I just cite a couple of studies here  that look at a non-cardiac general surgical procedures on patients on ECMO. This is actually from the group here at Lehigh, actually before I came back.  And you can see that they had 90 procedures.  And the reason I show this is that basically this study and other studies have shown the same thing. It's not surprising that a patient who needs a surgical procedure  is gonna select themselves out as a sicker patient. So they definitely have more complications. You have to deal with more bleeding. Now you have to deal with wound infections,  more pneumonias, more everything except the survival rates are the same. So, you know, so we get it. We're operating on sick patients  and they need the operation, we do the operation. And the other important thing about this study was they did have nine patients who had major perioperative hemorrhage  and that the need for transfusion selects yourself out.  The surgical patient selects themselves out as lower survivability. So you need to anticipate those bleeding complications and deal with them timely.  And the next study was just our friends at Temple.  Basically says the same thing, much larger experience. I believe they had over 250 procedures and they showed that again, more wound infections,  more pneumonias, more bleeding complications,  but same survivability between the patients who had procedures and didn't have procedures. So the, you know, what we can do at the bedside, we will.  And again, call us early, please.  So speaking of calling friends, our wonderful, more friends, our wonderful pharmacist, Bill, tell us how we avert bleeding and clotting complications, keep our circuit healthy  and get through procedures during ECMO. What do we need to do? So again, noting that heparin is probably the most commonly used agent,  there's a lot of variables we have to keep in mind. The intensity may depend on what kind of circuit you have whether it's VV or VA or also the nature of the circuit  because some of the newer circuits have shorter tubings and they're set up differently. So you have to keep this in mind. Often we're challenged that the technology  strips the pharmacology. And so we don't have great ideas with new technology as far as what the optimal level of anticoagulation is.  Keep in mind, we're not only anticoagulating the circuit, we're also dealing with the patient as well. And we have cases and Subha can also chime in  on the fact that sometimes we have an impella and at the same time as we're on ECMO because we're trying to enhance the blood flow  through the cardiac system and the ventricles and such. So it can be on either the right or the left side. So we also have to keep this in consideration  and in part of your equation and what you're gonna do as well as any other indications for anticoagulation, should they have a hypercoagulable condition and such,  this creates a challenge. We also know that in COVID, because our patient is COVID, obviously there's other reasons to anticoagulate the patient. In this whole process,  we really don't have a lot of standardization. And there's a lot of disagreement and discordance between approaches to measuring the effects of these agents.  And this is kind of how it shows in the LSO guidelines is that there's a lot of discordance between the various methods and there's poor agreement between the methods.  So the thing that's important here is I think to understand your method, how it works and also constantly look at gaps. This actually falls within the Joint Commission  Elements of Performance for Anticoagulation Therapy to look at these things and know how to improve on it. Maybe go on to the next slide. Oh, go ahead.  And I think when it comes to Impella or whatnot, and that's in the VA ECMO cases, you really need to take a number of things into account.  That's what I think makes the lack of guidelines, makes it because it's not a cookie cutter or a cookbook approach. You really do have to individualize it  with respect to the patient.  So when you're looking at the APTT, this is one of the interesting thing with mechanical devices is...  Bill, I think we lost your audio for a second.  Do you have me now? We do. Okay. Do you want to start with this slide over? Okay. So there's a lot of challenges with the APTT. Different institutions have different reagents  with different sensitivities. And when you look back and get into the details of a lot of the trials for mechanical devices that are multi-centered, they didn't necessarily control  for the different reagent sensitivities. We even learned with the heparin and the enoxaparin trials for initial DVT treatment is that the heparin arm may have been undertreated  because they did not control for this. So you have to take when someone says a device and your target range should be an antitinnative 40 to 60 seconds,  but you have an assay that's very sensitive to the heparin, you may be actually undertreating your patients. So it's important to understand your assay  and how it relates to the data before you make decisions on your target ranges. But this is one of the things that's important. And also labs between different hospitals,  even within the same system may have different reagents. So you always have to keep this in mind when you look at APTTs and know what your agents are.  And also when they change the reagent, you may have a different value of different target range and you need to also adjust every time the lab makes that reagent change.  One of the things that we do is we require the lab to notify us a month in advance of the reagent change and also give us the curves between the old reagent and a new reagent  so we know what differences there are and make the necessary changes before they put it into place. And then we have them put into place early in the week in the morning  so we can adjust all the therapies in the patients instead of waiting when no one's around to deal with it.  Another way we can look at this is the anti-TIN-A assay. It's a chromogenic assay, but there are variabilities. For example, one method actually spikes with antithrombin  and antithrombin is something that is an issue with ECMO patients. So you really need to know which method you're using. Are you using an anti-TIN-A  with the antithrombin added in this step? If so, you're going to miss the antithrombin deficiency that's occurring or to use a method that doesn't because between the two methods,  you'll get two different reagents.  So there's two different values in these patients. It's best to use the right reagent to calibrate your assay. And so obviously for these patients, we're going to be using heparin.  So use your anti-TIN-A assay and calibrate it to heparin. Noting that there is a low molecular heparin calibrator as well. It's one for all low molecular heparins.  And just as an FYI on the horizon is going to be actually the DOAC calibrators. It's just a matter of a short time. It could even happen this year with the calibrators being present  that people start using the anti-TIN-A to assess DOAC effects. And this might be helpful, especially if you're on a DOAC and you're switching the patient to an anti-TIN-A assay  because, and we published a paper and there's a few others that for at least 72 hours in general, but patients who have heart failure,  renal failure or liver failure, it may actually be longer. So we measured therapeutic levels of apixaban six and seven days after the last dose because they got super high  with their level in the first place.  The other thing I find with our ECMO patients is that sometimes their livers start to shut down as well and you get high total bilirubins. And because of the yellowing of the serum  that happens with the high T-billies, this actually messes up the anti-TIN-A and you might not be able to measure much of response yet you had a robust response present.  So they could be very anti-coagulated yet your TIN-A assay shows very little response at all. So it's important to know that. And to verify that is to look at a thrombin time  as a separate measure to see if that's truly the case and knowing your assays and what can go wrong. Also keep in mind when you're ordering, it's not a factor TIN-A,  that's for assessing clotting factors. It's a factor TIN-A activity assay. So don't get the two confused. Lupus anticoagulant actually can be risen  in patients with COVID related issues. So those are other things that you have to be cognizant of because we do know that some patients with COVID-19  have elevated prothrombin times as well as APTTs. Hence why the anti-TIN-A assay in a patient like this might be preferred because it's not influenced by the COVID disease.  This is just a table that I put together, just shows you all the different things that can go, arrive when you look at either an anti-TIN-A or an APTT. So neither is perfect.  And I think this is one of the reasons why we don't have really clear guidance establishing which one's better than the other.  But this just gives you an idea of all the different things. Note that the antithrombin deficiency patient, you might see a blunted APTT response,  but also depending on what kind of assay errors you're gonna see something different in the anti-TIN-A. I'm not gonna spend a lot of time going into this,  but if you wanna see this table, you can find it on the anticoagulation forums, centers of excellent sites, where I have a little document I prepared  on switching between the APTT and the anti-TIN-A assay that can guide you through the process. So Bill, what do you use routinely? And so what do you, in your ECMO cases,  what do you measure in terms of how frequent do you measure  and what tests, how do you approach that? So we used to do the APTT for a lot of years, but then we ran into a reagent change for my target range between the low and high was,  I had the target between 62 and 70 seconds. That was my range. And we felt that was clinically impossible to do with the new reagent. So we switched over to the anti-TIN-A assay.  And in a couple of slides or later on, I'm gonna describe a little bit of what we did when we compared the two approaches. But we use the anti-TIN-A now.  We actually did a whole thing looking at APTT, anti-TIN-A and ACTs. And we combined them all because for a period of a number of years, we actually measured all three.  And we found it's just a lot of discordance, but it seemed like the anti-TIN-A had a little bit more reliability, but it's a single center,  but they just don't all agree with each other. And that's the bottom line. I agree. We do very similar. We go with PTT and then TEG. And if there's discordance,  then we go with the anti-TIN-A as sort of our tiebreaker. But when we published our experience with comparing PTT with TEG, prolonged our time with TEG,  we found only about a 37% concordance rate. So only about one in three times in ECMO did the PTT and TEG correlate. Yeah, and I was gonna talk about this in a TEG slide,  but just to note that there is some centers that say they have better ideas of understanding the anticoagulation and a little bit better outcomes  when they actually combine the TEG with their normal assay. So they assay their anti-TIN or APTT every six hours, but then once or twice a day also do a TEG.  So it's like a confirmation step to make sure they're following the right thing and looking at it from a global basis.  So this slide talks about some of the other things we wanna think of troubleshooting and also introducing the activated clotting time.  Sometimes we have what we call heparin resistance, so there's no response. Here's some of the tricks that I use. We might find ourselves bolusing these patients.  So what I do is you give like a two or 3,000 unit bolus to these patients. I'll measure an anti-TIN or an APTT 15 minutes after the bolus, because I know I have a lot of heparin  in the system at that point. I mean, that really supersaturates the patient with the heparin effect. And if I get no response at that time, I have to look for other alternatives  or at least know the assay I'm using is not gonna help me no matter how high I get with the heparin levels. And there is some pediatric data,  I think it came out of John Hopkins a number of years ago that shows the higher the heparin doses you get, especially when you're over 30 or 40 units  per kilogram per hour, it is a predictor of mortality. So you have to be cautious of what you're doing in these populations. Also, you wanna look for INRs and thrombin time  is again, a useful test for us to check and make sure we're actually believing what we see. Sometimes you can do the ACT, but there's two ACTs and we have to be aware of this  because a lot of literature says ACT, but then I ask which one? So in the operating room, we use a high range ACT because it's measuring the higher effects  of heparin it's occurring. It's not a test designed to measure the amount of heparin effects in someone who's got a pulmonary embolism. It'll actually be a normal ACT  if they're very anticoagulated. The low range ACT, which is typically the one we might wanna see. And you look at the ELSO guidelines,  they're kinda weak on what they wanna say about it. What ranges, it probably depends on what your baseline values are, whether you wanna go 180 to 220 seconds or so.  But this is a different test. It's the same machine, but a different calibrating card. So here's a study we did at our institution showing the difference.  And it really comes into play at higher values where it separates more, but they are different tests. And so you have to keep in mind when you're looking at this  is which ACT are you truly looking at it? But sometimes we use a low range ACT. It's a point of care method to see if what we're seeing is believing.  The more tests that line up into one court gives you more confidence that maybe that's the approach you wanna use. But also make sure you're calibrating everything correctly  and using the correct information and interpreting it.  So when we deal with COVID-19, obviously this is a combination of a cytokine storm  that creates a hypercoagulant or coagulopathy that puts these patients at risk for thromboembolism. I'm just gonna demonstrate with this slide  that it is a reaction between your inflammatory system and your hematologic system. And so they tend to be prothrombotic. Obviously the critically ill patients on ECMO  are gonna be higher risk in these populations. And the high D-dimers, are two predictive factors for concerning for the coagulopathy. But this coagulopathy may be also  micropulmonary embolic processes that may be a little bit more resilient to your anticoagulation therapies. So this brings up a whole nother challenge for us and our patients,  because they've got COVID, their lungs are shot, they're on high oxygen flows, they're gonna be put on VV-ECMO. Now we have to coagulate the circuit  as well as keep the patient from clotting. And D-dimers are also difficult in these patients. I mean, I think the highest D-dimers I've seen in one of my ECMO patients was 50,000.  And it's really careful because the D-dimer is really not a very sensitive assay. Once it gets to a certain level, it just shoots up. So it's important to keep that in mind.  And then what level of anticoagulation? A big challenge, because maybe they don't need to be therapeutic, but on the circuit we are. But we have to look at this  plus the risk of bleeding in these patients.  So just looking at some of the abnormalities, obviously I mentioned the pro-time elevated D-dimers and possibly it seems like it's DIC, but there may not be as strong of a cytopenic  in these patients.  D-dimer levels greater than three or six times your laboratory normal have been shown to be statistically associated with thromboembolic events from the early Chinese data.  There's some recent meta-analysis that the lower the platelet counts go, the more severe it is. And this is always a challenge because these circuits cause platelet counts  in thrombocytopenia. And how much does this data relate to the ECMO population is unclear because it's a separate driver for it versus the COVID related driver of thrombocytopenia.  So be very careful when you're looking at this. Some people always think about HIT. Actually, we all should when you're using any sort of heparin product,  but because of this inflammatory storm, it can actually cause a false positive on the ELISA. So you might wanna look at more specific tests that look at actually the effect  of the platelet function itself to confirm whether they have HIT or not. So be very careful just not to use the ELISA alone and then go down this avenue of,  oh, this patient's got HIT. The other thing with COVID patients is the thrombocytopenia may be delayed, making it difficult.  So the 4T score may not be as reliable in this population. Obviously, you need to also correct for any bleeding issues you have with these patients.  As Marie kind of mentioned already, there's other things like antifibrinolytics and such that might be used. And keep in mind that generally with the thrombocytopenia in COVID,  the fibrinogens tend to be normal or higher  until you get to the very end stage. And unfortunately, these are some of our ECMO patients who get end stage and then they get,  you start seeing that depression in their fibrinogens.  So when you're looking at the circuit, one of the things is we are anticoagulating the circuit. We need to assess the circuit real carefully as to what we're doing.  The COVID guidelines really don't provide a lot of specifics on what we need to do. There's actually a new set of pending COVID ELSO guidelines for COVID and ECMO.  And they really just say nothing specific, use what you use in your center, but you may need higher intensity of anticoagulation. Some centers have actually moved to bivalve rodent  and there's some preliminary data that since the direct thrombin inhibitors turn off thrombin and thrombin is a mediator of inflammatory properties,  that maybe you also get that anti-inflammatory benefit that heparin gives you independent of the anticoagulation effects. There's not a lot of data here.  It seems to line more up as far as what you might see with your own center's experience in what you're doing. So we really don't know how high the APTT ratio should be  if you have COVID and you're on the ECMO. So it's really unclear where you should go and it's gonna be a lot of clinical gestalt or judgments you have.  One of the challenges with the direct thrombin inhibitors, however, is that you can see a plateauing of the response where the APTT is not rising yet you're giving more drug.  Here again, the thrombin time can help sort that out but this is a challenge we actually frequently face in these populations and using the APTT for doing so.  So again, when you see and you're upping the rate and the APTT is not changing, check a thrombin time. You may have to cap your dose. Thank you.  So gentlemen, thank you. To summarize our VV-ECMO case,  it's pretty clear from the conversation we've just had that VV-ECMO support requires ongoing intervention  to balance our risks between bleeding and clotting. That this management involves ongoing and I can't stress it enough, multidisciplinary assessment and intervention  on a moment to moment basis almost. I think it's pretty clear from what Mark has shared and Shuba that surgical interventions are feasible  and are safe with coordination, with planning but they're not gonna run away because the patient's anticoagulated.  Even though heparin is still our most frequently used VV-ECMO anticoagulant, we still have variability in how we use our targets, our tests and our goals of therapy.  And there's a lot more room for research in that venue as well. We are increasing our experience with direct thrombin inhibitors as alternatives to heparin or in some institutions  as the frontline first line agents for anticoagulating our circuits.  But unfortunately, with all we had to learn,  we still have more to learn given the complexity of the coagulopathy that we see associated with COVID that makes us all start from square one.  Closing thoughts, gentlemen, before we move on to our next case.  I think we would all collectively really wanna highlight the multidisciplinary aspect of it. I think in our ECMO rounds daily,  we also have the benefit of having a brilliant pharmacist like Bill  help us with anticoagulation to be able to manage the subtle nuances in terms of this.  And I think that really helps. I think that you have to listen to the nurses, you have to listen to the perfusionists who are looking at the circuit multiple times  throughout the day. And I think we, Mark and I were sort of joking,  you're either more afraid of bleeding or you're more afraid of circuit issues. I'm more afraid of bleeding, so I tend to lean a little bit more in the cautious approach.  But again, you have to sort of manage the two within that.  Yeah, and I would add, I mean, we all work at academic centers. These should be attending to attending discussions. I don't wanna offend our outstanding house officers,  but you gotta pick up the good old thing that actually have these telephones and talk.  Yeah, and I think, Mark, I think that's a really good point, especially if you're in a system where you go on for, you rotate, you're on service for a week at a time,  and then you move forward. It really requires communication between your own colleagues, because again, these are not people who are on for three or four days.  These are people who are gonna be on for a month or so, and so you have to keep that in mind. Yeah. And if it were easy, we'd be doing it in our garages. Oh, wait, Dr. Bartlett did.  Dr. Bartlett did, yeah. Okay.  Let's move on to our next case. So this is a veno-arteriolectal case. We have a 68-year-old gentleman  with a BMI of 41, type 2 diabetes, hypertension that may or may not be controlled somewhat with his lisinopril, who has a stenotic aortic porcine valve and severe MR,  who presents for repeat sternotomy for both aortic and microvalve replacements. His first cardiopulmonary bypass lasts a long time.  It's complicated by a significant amount of bleeding and unfortunately, vasoplegia after separation from bypass. Second bypass run is initiated,  continues an additional couple hours, continued bleeding, ongoing vasoplegia, separation attempt, and so VA ECMO is initiated before the patient leaves the OR  the chest is left open, the bleeding is continuing at about 300 mils an hour, and the patient is not making any urine.  The team arrives back into the CBICU and the team there is concerned about anticoagulating the ECMO circuits as well as protecting this new valve in the aortic position.  And they're worried about doing so with the patient's continued bleeding. They also, given the fact that the patient is not making any urine,  they're concerned about when they will need to initiate CRRT and if there's necessity and what options they have to anticoagulate at least that portion of the patient's circuitry.  So, Chuba, how do you manage this?  Yeah, so I'll put in a couple of like, you know, with respect to the case at first. So the first things to keep in mind are, are you centrally cannulated or peripherally cannulated?  So the advantage to, there's some, you know, hemodynamic advantages to central cannulation  with respect to immediate post-surgical. One, you're there in the chest already. You don't get things like Harlequin syndrome later on. You know, everything's antegrade flow.  You can probably vet the patient directly right at the time. But there are disadvantages because you, with the chest left open, there's no sternal apposition.  And, you know, there's gonna be some element of bleeding. In this case, there was some ongoing bleeding concerns. And so the chest was left open.  So your first question is, can I actually close the chest? Or, you know, is the patient hemodynamic gonna get to tolerate that? If you're going to go peripheral,  there are hemostatic advantages, but there are also, now you introduced, you know, a potential risk of leg problems and whatnot. So I think the key thing as a surgeon  is you need to try to come out of the operating room as best as you can. Before you can blame a lack of clotting factors, you need to make sure that it's not a lack of proline  that's causing the problem. So you need to sort of be very confident that you've done your best with respect to surgical sites. So then you can leave it to your medical colleagues  and critical care colleagues to try to like save the day  transfusion and resuscitation. Now, with respect to when to transfuse, you know, again, it's hard. These are sort of the general also anticoagulation guidelines.  I think these are numbers that would be considered for sort of all ECMO in general. I think post-cardiotomy, especially the sense of bleeding  is probably a little bit of a different beast because you've got, you know, your surgical sites,  your chest open. But in general, you do try to aim for certain thresholds. I think that most people try to take a hemoglobin nowadays of at least eight.  In the past, especially in VV ECMOs, people would tend to run a higher hemoglobin and a higher hematocrit. We tend to do that in VV ECMO when we are hypoxemic  and making sure that we get adequate oxygen delivery. I think the key thing to keep in mind is with respect to, it's not just a hemoglobin.  You need to take into account things like lactate, SpO2,  in terms of gauging what level of perfusion you're at. In the operating room, we use NIRS or near infrared spectroscopy to give us an idea of cerebral monitoring.  So if we see the NIRS dropping, we will tend to transfuse up a little bit higher with respect to that. I think with respect to FFP and even antithrombin,  which FFP has antithrombin, so I think fixing that I think is helpful. Nowadays, more and more in the operating room. We're more aggressive about using agents like Kcentra.  I think with respect to that fibrinogen, in general, in a post-surgical setting, you wanna try to keep the fibrinogen at least 150 or higher. I think in general,  we'd like to try to keep it no lower than 100, and then you'll treat your platelets accordingly. So I think you have to take into account what your clinical context is.  Immediate post-surgery, probably err on the side of being a little bit more aggressive, again, using smarter transfusion thresholds strategies that we'll talk about.  But those are sort of, I think, general guidelines with respect to that. And I think the last thing I would underscore is that just because there is a coagulopathy  does not mean that there's not surgical bleeding. So from a surgical humility standpoint, you have to be willing to accept the fact that there could be.  And ongoing, the last thing you want as a surgeon is the critical, you wake up in the morning and you come in at 6.30 in the morning, and the intensivist said,  oh yeah, we transfused him 14 units of blood. And you're like, wait a second, you guys did what? So I think critical care and surgery  really has to communicate closely with respect to that.  So, Bill, your thoughts on what other rabbits you have in your hat? So obviously when we have, as Subha mentioned, low hemoglobin, somatic rates and such,  we're gonna be transfusing blood, obviously.  But also sometimes for blood conservation or more potent effects, surgeons or situations might ask for prothrombin complex concentrates. There's several out there available to us  that might be used in different centers, use different agents. It's important to really understand how you use these agents. And in our patients, even in the OR,  when I'm in the OR using these, or even on the floor with the ECMO, you have to look at what kind of time you have. And if you have time to get your effects,  then you can probably titrate. These agents work within minutes. So why we have to suddenly throw hemophilia doses at these patients, which can be large doses,  when there's plenty of time to titrate to effect, may be an advantage and also may minimize the amount of thromboembolic complications. I think that's something we learned  with the recombinant factor VII. In the early years, as everybody gave 90 plus mics per kilo, we found success in the OR using just one milligram doses and got what we needed.  Looking at the field bleeding, the chest tube outputs and such. So just know how your approach is. And I'm always hesitant when you wanna add and combine these agents,  because all I've seen in most of my career, outside of the OR setting, where they're gonna be on some sort of antifibroanalytic to the most case.  When you start combining these things at the same time, we've just got a lot of clotting. So keep that in mind. Again, you can titrate post-operatively to effect.  Remember that the citrate in blood products  is gonna lower your calcium. So you need to sustain and maintain adequate calcium levels, because that's part of your clotting cascade.  Pathways is with calcium at two different steps. And also more of an issue in the OR is that when you're hypothermic, that actually impairs the clotting cascade  and it can shut down. So during those periods of time, you're not gonna have as much effect. And also if you have to be using bivalve rodent during that case,  the hypothermia is actually gonna decay the enzymatic degradation of bivalve rodent. So we've had cases actually, where we're using bivalve rodent and doing open heart surgery,  where the ACTs are climbing and we just shut it off until they start dropping again.  But also, after you come out of the operating room, for about six hours or so, you're gonna see a rebound of heparin back into the tissues. And it's gonna be sufficient enough  to treat a pulmonary embolism. In the OR, they'll say, well, we gave all this protamine and then we did an ACT. Well, the ACT is normalized,  but the ACT does not tell you the lower levels of anticoagulation. So you may miss it. So always keep that in mind. And sometimes we give a little additional protamine dose  of 25 milligrams or so, if we have undesirable amounts of chest tube output. In this whole thing, we need to assess the balance of risk and bleeding. And also keep in mind,  I talked about some of the pharmacologic interventions, but sometimes what you need is a good stitch because it may be a larger vessel that's bleeding,  or sometimes they might choose to use topical agents around a certain area. So I don't know if Subha wants to say anything more,  but those are some of the things you wanna think about with transfusions. Absolutely. I 100% agree. I think you have, just because you were not,  there was no signs of surgical bleeding at time zero, doesn't mean that two hours or four hours later, something becomes more apparent.  And I think you have to just have the level of humility to recognize that sometimes the best thing you can do  is just take them back, get the clot out, and then, you know, and get a look. I mean, I would much rather do that sort of at eight or nine o'clock at night  and then sleep for the rest of the night than be worrying about it all night. So I think that's a reasonable, certainly reasonable.  Yeah, I agree. Subha, our pharmacist here, Bill, I know you've told me that you haven't found the lowest dose of FEBA that you could, that's not effective.  And I just wanna make a point here. Our pharmacist came to us in the bad old days when we used recombinant factor 7A to the tune of,  as you said, you know, 90 to 100 units and maybe even more.  And pharmacy came to us like, can you use a smaller dose? And we said, no, we're surgeons.  We go big or go home, you know, we're using the big dose. They begged and pleaded with us and we said, okay, fine. So we cut our dose in half.  And I said, you know, how will we know if it works? Well, Subha knows, Bill knows, you know when these patients have a coagulation system that's working,  either in the operating room or at the ICU bedside.  It's just obvious. In the operating room, you start to see clots. At the bedside, the patient no longer is requiring as much blood, you know, and their lactates,  they're getting better. And it's, you know, maybe it's because I've been doing it for a long time, but you do, you can just sense when that coagulation system  is now doing what it's supposed to do. Right. In my experience- When you're in the OR with the chest open and you see blood that's sort of like  a kind of light colored cherry Kool-Aid that you can just, that's almost transparent. You know that, you know, it's not ready. It's gotta be fixed. Bill, you were saying?  Yeah, I just say that, you know, my experience with open heart surgeries, and we actually went and measured this. We find that one milligram, sometimes a repeat dose  is adequate in most cases to stop all that field bleeding. We'll use a factor seven. Now the PCCs are used, but there is an actual study that was showed  that when they use higher doses, that they interviewed the surgeons and it was like 40 or 50 cases that they did. And the surgeon said, we had no complications  and all 50 of these cases had had thromboembolic events, but it happened two weeks later. Right, right, of course. So it's important to think about whatever you're doing  to reverse the bleeding is that there can be long-term effects. It's like setting down the smoke or something, the spark, and then the flames can disrupt  into a big thromboembolism sometime later. So that's why I've always strived to use the lowest dose necessary to get the effects I need. But obviously you can't have a patient  with sustained bleeding. You need to stop it. That's what's really important as well. And Bill, to highlight something you had brought up earlier is that this is where,  in I think the best transfusion meetings are like the blood conservations, getting pharmacy surgeons, critical care, a number of different disciplines involved.  These decisions are so much better in terms of what dose to start at, when to do it at, on a Tuesday morning, not in the heat of battle,  so that you have a clear escalation algorithm. So that when it's nine o'clock at night, you're on your second case, it's this double valve, you just want to get out of the OR,  everybody sort of is on board in terms of how you're going to escalate and go forward. And you're not reinventing the wheel or people aren't quoting some study  that they heard in some Italian, whatever random study that said they use this, you've got this thought through. Yeah, and these patients are in ECMO,  but the other part of it is that if you do use these agents, we're very much on a high vigilance of looking at when we can start prophylaxis as soon as possible,  because we know we've set down a possible thrombotic storm.  The good news, however, is our patient has stopped bleeding  and he has started peeing and his chest is closed and folks are targeting weaning his ECMO in the next day or two.  However, by the next day,  the team feels that they are seeing escalating heparin needs  because they're having difficulty achieving their pre-specified targets. The platelets are difficult to support. They have increasing platelet transfusion needs  to meet their targets. And there's fibrin and there's clot starting to build in their circuit.  So Bill, what are your thoughts about this deteriorating scenario?  Want to change the slide, please?  So one of the things is obviously looking at which assay you're using. Again, most of the comparisons for the APTT versus anti-TEN, they are not in the ECLS populations.  This is an area where we have a gap of information about how to do it and what the outcomes are for thrombosis and bleeding is always in anything  that's retrospective, very difficult to really attribute to whether it's to the anticoagulation therapy or something else. But you also have to keep in mind,  as I mentioned, to know your reagents and the sensitivities and any sort of factors present that might influence those results. And we do see, even when we look at changing  between the two, not alone in the ECMO populations, a lot of discordance between the two approaches. One of the things that we did,  and this is a paper that we actually have accepted in ASIO that's going to be published shortly, is when we did switch over for APTT to the anti-TEN,  we went back and compared our VA ECMO patients. These are adults. And we noted that when we went to the anti-TEN assay, we actually got in the target range sooner,  which is similar to all the other studies with going from APT to anti-TEN for treatment of thromboembolism. But no one ever really looked at the heparin rates. So we actually did.  And we found out that actually using the anti-TEN in our facility resulted in lower heparin requirements to these patients.  And also, they're more frequently in the target range. So just some of the things you think about, you actually might see a difference in heparin rates,  and that might go into your risk for bleeding or thromboembolism in these populations. Just know your assay and be aware that there are things that can go haywire with them.  And you have to be aware of it and always look at the big pictures. And I think that's why some people have looked at the tags. And Bill, there is a developmental hemostasis impact  on how you correlate the two as well, right? Yeah.  It's hard for us. We could not measure that easily because of documentation. And when we first did our first ECMO series, we did a series in PEDS, we did a series in DALTS,  and we published those. And we really tried to figure out thrombosis and bleeding,  even bleeding. It's just really hard to get down to the bleeding in any sort of retrospective analysis that you do. It's just very difficult to provide  any sort of hard outcome validity to it. Bill, could you comment on turnaround time for anti-10A tests? The anti-10A takes about 15 minutes to run.  So if your laboratory is all set up to do it, it can do it really quickly. It's just a matter of getting it there correctly in the right tubes and get it reported.  So sometimes if you have these things where you need them abruptly, they can be priority one labs, you set it with your lab, and then in those patients, they'll run it right away.  Yeah. And do you know, is there any point of care technology on the horizon or for that particular? Not that's quite reliable. Obviously the ACT, that's the advantage of it. Sure.  And then the TAG, of course, as we're going to TAG, it takes quite a bit longer to do the TAG. I'm not gonna talk a little bit about, too much about the TAG.  It's just, this is a way that we can get a better picture, a global picture of the patients. SCCM has had multiple presentations  by Dr. Shriver and others about the TAG, but it is a tool that can be used and you might get a better idea of your patient in these situations and might help confirm  how to transfuse or what you're dealing with and understanding your patient, not only from the thrombin, but also platelet and fibrinogen and also lysis. Again, I mentioned,  we sometimes use the lytic component of the TAG to see if we've got adequate lysis or even how we adjust our thrombolytic doses.  Now, when you're dealing with HIT in these patients, there's obviously not a lot of information and thrombocytopenia can be the result of the device. If you're scoring them,  actually they have other causes that's gonna come into a scoring method. It's hard to say, and it depends on the situation. So the 4T score is not very reliable  in patients who are post-operative. And this might apply, especially when you go into VV ECMO and all these patients who come out of the OR from open heart surgery  have pronounced thrombocytopenias. So there's a different scoring system you should be aware of. I'm not gonna describe it in detail, but man, it deals with time on pump,  an initial drop in platelets to recover and a subsequent drop, which Forkinton has described in the past. And so there's a lot of challenges with it.  So without going into a lot of detail, we actually did a review that was published in the Journal of Thrombosis, Thrombolysis, I was one of the authors of this,  dealing with the many challenges with the devices and anticoagulation in the setting of HIT, whether it's a pre-implementation phase during post  or recognition at the bedside with laboratory surveillance. And there's just a lot of targets that may depend on multiple factors. If you wanna learn more about that,  I'd just refer you to that paper.  And also keep in mind that there's variances in the DTI response to the APTT. So here's another study that we did as well. And we sent out the APTTs spiked  with a certain amount of direct thrombin inhibitor presence there to all these institutions. And when there are these 14 different assays assessed  and what they found with it is that there are two outliers that are a lot more sensitive than the others. Another group in Florida did the exact same study  and found the same information, but we came to opposite conclusions because when they looked at the whole big picture, and this is a challenge with statistics,  they said there's no statistical difference. But if half the assays were more sensitive and half are the ones that are grouped and the ones that have similar symptoms,  it's highly clinical irrelevant. And if you look at your statistics that way, it's very statistically significant. So it's important to know your assay and how it might respond  because your ranges may be different if you have a more sensitive assay to the direct thrombin inhibitors, this does occur. So it's something to keep in mind.  If they're not responding, again, I mentioned checking the thrombin time, but also sometimes if your institution makes these bags up in pharmacy  for the specific direct thrombin inhibitor, you may need to check to make sure that the bag was done correctly if you're not getting a response.  And also just the issue of, okay, so when can we stop these?  And no, these effects are diminished or gone away. So for you pharmacists in the group, it's kind of a little bit of what I'm gonna show momentarily. But when you stop the heparin,  you're gonna see that their patients are on lower DTI doses, it's gonna take longer for them to drop away versus someone who's on a higher DTI dose.  So keep that in mind when you're making this decision. If they're at doses of 0.25 milligrams per kilogram per hour, they're probably gonna eliminate more robustly  than someone who's at a lower dose of 0.05 milligrams per kilogram per hour. So that can give you some sort of hint as far as where you're going  and how long it'll take for the drugs to go away. In addition, when you're switching over, so this slide talks about changing from heparin to DTI,  you stop the heparin at the same time you start the DTI effusion. And so if patients are requiring a dose adjustment where they need to lower dose,  you might see at two hours that the APTT has not dropped into the new range that you're gonna use for the DTI. Remember the two are not the same range, although it's the same test.  And so watching that decline gives you an idea earlier whether you need to drop the rate and especially if it's going up, you may have too much drug on board  depending on what dose you chose. So this is one way to ease yourself every two hours. I've done this in patients who are infants to adults  that this seems to work as far as following the trends and seeing where you're going so you can get to the right place you wanna be.  And steady state remember can be longer in these patients because their elimination is poor. So it's not like what you read in the package insert  nobody's steady state at two, three hours, it could take longer.  And this just shows with our pediatric series we published a number of years ago that the bivalve rutin doses are all over the board.  So there's no real agreement between populations. There's a lot of variability. We also sometimes did boluses of 0.1 or 0.2 milligrams per kilo, but we never really assessed that  because we're not doing a lot of blood draws an hour after the boluses to see what it is. And I don't think anybody's really got a good idea.  Sometimes if you need an abrupt response, suddenly you can't do these many boluses, but we're not sure what the outcome is that in practice. But this just goes to show  that the doses are all over the board and there's not a lot of consistency  even amongst populations like pediatrics where you don't have a lot of these other disease factors to deal with as well.  And then of course, the controversial issue of antithrombin supplementation. First of all, we want to think, oh, they've got antithrombin deficiency  because the heparin is not working. Well, you have to check your assays and other things. Could there be another reason for this?  And this is why I recommend using thrombin times or tags or even an ACT in the low range to sort out what's going on before you suddenly come to the idea  that it's antithrombin deficient. There's not a lot of agreement as far as what to do with antithrombin depletion and what levels you should give antithrombin if you give it at all.  Also remember some of the anti-TAN-A assays add antithrombin to the process and you might miss it. So know your assay and how it's done. Adding antithrombin doesn't seem to overall  change the heparin dose. And we looked at this in our institution and we would give the antithrombin supplementation and we really didn't see the heparin requirement change.  The dose just didn't go anywhere. Although we did see a little bit more improvement in the responsiveness to the coagulation studies. Remember the FFP as was mentioned  has antithrombin in it as well. There is some recent data suggesting that low antithrombin levels in patients on ECMO have increased mortality,  but also that when you add antithrombin supplementation is associated with an increased risk of thrombosis. We really don't know. And also keep in mind that antithrombin  is a very expensive substance. What do we do at our institution? Well, at least with the adults for sure. We actually think about using a direct thrombin inhibitor  instead to get around this because of the cost, but also the ease of monitoring. Many centers are actually going to DTIs as a frontline therapy as well.  So that's the approach we took. Other institutions do other approaches. There's no full agreement as to which approach is better in these patients.  Bill, you know, it's interesting. We have, we work with hematopathology colleagues and they do a week at a time. And there is no topic amongst our Hempath colleagues  that creates more divisiveness of opinions than what to do with AT3, you know, what to do with the antithrombin. So it's literally each week for us,  it could be very different, but I agree. I think this is, I think we also have, we used to do a lot more of supplementation, AT, antithrombin concentration.  And now increasingly we've moved more and more towards if we're encountering this problem to just move to DTIs. Yeah, and they also guidelines are not really clear.  I mean, is it less than 30 or what is it that you need to be at a threshold to do this? And then once you do it, what targets do you need to achieve?  And then you're doing this every 12 hours or so.  There's just a lot to it. It's not the easiest thing to also really monitor and follow through and know what you're doing with the whole process.  And it really impressed me that I expected when I gave the antithrombin to these patients, my heparin doses would have to drop. I just don't see that happening.  So there's just a lot of conflicting data about antithrombin and antithrombin and its use. The benefits are not clear. And again, the harms is noted there.  So there's something that you need to think about for your institution when you go down this line is how you wanna do it and approach it. Again, reiterating that for us,  we just switched into a direct thrombin inhibitor and made it a lot easier.  And then the last thing I'll probably mention is post-cardiac anticoagulation. So keep in mind that they come out of the OR after open heart surgery,  and it's always good to know what happened in the OR. So it's really good. And for me, actually, as a pharmacist, I go in the OR and I understand what's going on  in the surgery itself when we run into these problems. I'll note that sometimes we want to knee-jerk and give these antidotes for these patients  who may have too much of a DTI effect or especially with the DOACs and such. Keep in mind that as long as that agent is on board in the system,  you may not be able to get the heparin to work or you may have to give more and there's not a lot of clear guidance. So always when you have patients  who are on ECMO for some reason, you have to be cognizant about how you want to do reversal approaches. And also understand your devices and the goals, again, may vary.  I mentioned this six-hour rebound and balancing the importance of bleeding and thrombosis  that you're going to go at, you know, intervals, and the surgeon's not going to want to be closing for hours  for a patient who's bleeding, and then all the blood that you have to transfuse to deal with that, so they may use  concentrating clotting factors in such a front. When you're in the OR, watch what's going on with the different,  there's a canister, actually, you can look at in these patients, and the canister has a filter in it, and if you see the blood crossing  the filter readily, they're okay, they're anticoagulant, but when you start seeing the levels on both sides diverge,  that's telling you you've got maybe some clotting going on in that filter. It's just one indicator, as well as the ACT  and what the surgeons are seeing in the wound, that you need to keep in mind, so you don't over-reverse the effect  or over-create a prothrombotic effect, until they're able to close the chest, if they even are able to close it in the operating room.  But keep in mind the circuit, as well as the patient, and when you're on the ECLS circuit, one of the things I look at is a delta piece,  you know, what is the difference in pressure, and if it's rising, you know, when it gets above 20, you're paying attention to it,  and my COVID patients, they'll sit up in the 30s for a while, but you have to keep in mind what the circuit's telling you  about possible clotting and issues that go on, and what trend are you going on to, as well as looking at the tubing  and visual inspection of the circuit. I actually take my cell phone and take a photograph of the circuit sometimes,  when I can see, depending on the circuit I had, the newer ones are a little bit harder to do,  but then I can go back the next day and look at the same area and see, is that clot expanding or not?  I have some sort of baseline to work from. Remember, with impella devices, you have to consider the heparin and the purge,  as well as the IV heparin, to get the total dose in these patients, and if they're on hemodialysis,  and a lot of these patients may be on continuous renal replacement therapies, keep in mind also that that will actually remove the bivalve rudin.  So, one of the things to note is when they go on or off dialysis and they're using bivalve rudin, that it might impact what you see with your coagulation assays and measures.  So, Bill, what I would add also to this is, from a cardiovascular surgical standpoint, there are a couple of comments.  One is with respect to bleeding. So, in general, you can get away with holding anticoagulation, in general, longer than a lot of people suspect.  I mean, I've seen people who want to start anticoagulation within 2 to 3 hours, but you can usually get away with 6, 12, even 24 hours.  We've even gone 48 to 72 hours without anticoagulation.  The caveats to that, though, the patients, the alternative, however, what you have to be careful of is LV thrombus and LV thrombosis.  And so, the patients who are more vulnerable to that are people who have new prosthetic valves and then people who are not vented.  So, if you're vented and there's very little blood flow in the LV, that's probably a little bit safer than if you're not vented, you know, or you don't have an impella and there's blood that can pool within the LV itself.  I think the other assessment you have to make is what's the level of LV contractility that you have?  And you can tell that off the arterial line based upon pulsatility. You'll see that on echo.  But if you have very little pulsatility, I mean, the ventricle just sitting there, then you're at much higher risk of thrombus formation.  So, I would say somebody who gets a new valve, whether it's tissue or mechanical, a new valve, somebody who has very little pulsatility, somebody who is not vented, for example, that patient is at much higher risk of LV thrombus and even potentially valve thrombosis.  Those are the patients we'd probably be a little bit more aggressive about in terms of starting anticoagulation.  So, I think these are some of the surgical decision points that can help work.  And again, to underscore, this requires really close communication between the surgeon, the critical care providers, the pharmacist, the whole team to understand how you're going to weigh the risks and the benefits and to try to get on one message.  And I think the other thing too is if they come out of the OR and then suddenly you want to put them on ECMO is that within that period of time, a lot of times they may not even need the heparin bolus because they have heparin effects.  I don't know if you want to comment on that too. Yeah, no, no, absolutely. You can get away without the heparin bolus or a smaller bolus than the full dose in terms of it.  So, I think those are certainly relevant for that.  And this just goes to show that we sometimes deal with not only the red clot, which is thrombus, but we've experienced in rare cases this white clot.  So, you can see the one to the left here, you see all the little white clots in there. And this may not be an issue with thrombus formation.  It may be something with platelets or fibrin and something else. So, you also have to look at the nature of the clot of your circuit.  And this can happen not only in the oxygenator, but it can occur in the tubing as well.  So, when you're looking at HIT from interoperative to some of the PERLs is most of the data, and there are some clinical trials looking at bivalrudin, and hence why guidelines recommend bivalrudin is probably the direct thrombin inhibitor that you use in the OR just because more data.  But with bivalrudin, you need to prime the circuit and also consider that in stagnant blood, it starts being decayed because thrombin is the enzyme that removes bivalrudin's effectiveness.  So, you have to citrate the cell saver and also keep in mind that the surgeons might see gelling in the field pockets of blood, and they may think they don't have adequate anticoagulation.  But with bivalrudin, that may not be the case. Again, note that hypothermia can shut down the clotting cascade as well as remove or reduce bivalrudin elimination.  Keep in mind, too, that there's other methods.  Sometimes with HIT, they may actually give an antiplatelet agent like tyrofibran or reptifibatide first and then start to heparin with the antiplatelet agent, blocking the effects so you can actually heparinize the patient and actually reverse them.  And that's also published in the literature as well.  And then this just goes to show us, just kind of showing, telling you before about the related elimination and when the effects are going to decline.  So, this is just a little bit clearer than the other diagram, but patients on lower doses probably have poor elimination.  For you pharmacists listening, of course, is that initial lecture we had that the concentration in the plasma steady state is a relationship of how much is going in versus how much is being taken out or elimination.  And it depends on how high your anticoagulation effect is in the first place. Super high levels take longer to go.  And if they've got low doses that got you there, it might take a long time for it to clear out.  So, you want to look at those two variables or variables to get an idea of when the effects might wear off in your patient because it's going to depend on different things.  And the best way I have to understand how the elimination is, is look at the dose that they're receiving. Low doses, probably long. High doses, it can go away faster.  So, to summarize our VA-ECMO patient case and discussion, we recognize that VA-ECMO is often complicated by postoperative bleeding and that an adequate balance between our bleeding and clotting issues often requires transfusion of multiple components.  We have novel hemostatic adjuncts that we can use that are often administered when we're trying to make the bleeding stop.  But the optimal usage, optimal timing, optimal dose, optimal patients, and optimal risk-benefit profile are still largely unknown, despite having a lot of these agents around for a while now.  Working as a team, we have to be transparent about discussing that surgical hemostasis is critical, whether it is primary hemostasis in the OR or subsequent bleeding issues that come about later in the ECMO course.  The challenge in monitoring our ECMO anticoagulation makes it sometimes difficult to titrate our therapy, and we need multiple different methods, multiple different testing strategies to decide where we think we're adequately anticoagulated.  And old tests are now new shiny toys.  Our viscoelastometric testing, our TEGS and our ROTEMs, may provide insight into our balance and our management, and certainly at some institutions are part and parcel of how they manage their ECMO.  We see and will see more as heparin is used more and more and patients live longer and longer, that heparin-induced thrombocytopenia hits, complicates our heparin use, and the direct thrombin inhibitors at this point are our usual alternatives, but they provide their own unique administration and monitoring issues.  And there's far more experience to be gained using those.  Any closing thoughts, gentlemen?  No, I think this has been a comprehensive look. I think multidisciplinary collaboration is the key to successful management.  Yeah, I would echo that. I did have a question. Any sense of how many ECMO centers are using DTIs as their first line anticoagulation?  I've never seen a survey as to how many are or not, but there are several major leading centers in the United States that are doing this now.  I'm a neighbor to Mayo, and Mayo is going to pretty much DTI for their frontline, first line, with good experience and good outcomes.  Yeah, we're discussing it. I think just you have to keep one thing in mind is that the patients still probably need to get their initial cannulation with heparin because it may take too long for the DTI to get there, but otherwise for the continuous infusion.  For us, when we saw and switched our patients to bivalrudin is that we actually noted prolonged circuit lights, but there's conflicting observations in the literature about that.  But that's always been one of those attractive things is that the circuits last twice as long as what we kind of were seeing. That might be an advantage as well.  I agree. I think that with COVID, as we've gotten more experience with bivalrudin in the COVID setting, I think post-COVID, many of us will probably make it easier to just stick with DTIs as a first line agent.  I think that the effects of what we learned in COVID, I think some of that residual will probably carry on going forward now that we have more experience with using it.  All right. Thanks, everyone.  We'll wrap up. One more slide to me. Well, what we're going to do is the pre-recorded portion of this talk is now over. We appreciate your attention.  And we have about 12 to 15 minutes for live questions and discussion. And that time will come as we cease the pre-recorded session. So thank you, everybody.  And stay on with your questions. We've been tallying them as they've come in through the chat. Talk to you in a minute.  How long their last dose was and, of course, anything, as I mentioned, that could impair their elimination. The baseline anti-TENA is elevated in these patients. It's going to be hard to know exactly how to adjust your heparin infusion.  And you may have to go to the APTT for a period of time until it washes out. So that's really a factor you have to keep in mind when making these decisions. If the baseline anti-TENA is less than 0.5 or 0.7, we figure that it will probably wash out pretty soon and we can probably rely on the anti-TENA assay.  Good. I actually came up with a question on my own. Mark, so when you've talked about the fact that you can do a lot of procedures at the bedside now and that, you know, and Shuba has talked about the fact that we do a lot of things because of COVID-related sensitivity to potential contamination and infection.  Are there specific things that bedside teams should get set up for you to optimize the procedure at the bedside? And are there still things that we just really should not try to do at the bedside and really do need to go to the OR?  Yeah, Marie, that's a good question. Of course, for instance, in my group, we have a kind of a spectrum of comfort level of doing trachs and pegs at the bedside. We've been doing them at the bedside for a long, long time here. But COVID kind of changed that. You know, we really try to be at the bedside for the most common procedures we do in these patients.  So I'd say virtually all of them are done at the bedside. Now, certainly a laparotomy can be done at the bedside, and we not infrequently do that as well. And the people you need to have at the bedside, of course, is your OR scrub tech, an OR circulator. You may have a CRNA at the bedside in case there are some issues.  Generally, these patients are going to be on sedation and paralytics already. So the need for that is not as great. And don't forget your perfusionist. If you think you're going to be running into a lot of hemorrhage, you really want to get the cell saver in there and be able to give that blood back to the patient, just like the patient I described in the presentation.  Now, we can look and always say, you know what, this is going to be too much to do at the bedside. And we're just going to have to, you know, bite the bullet and go to the operating room. Extremities, you know, a fasciotomy can simply be done at the bedside without much difficulty.  Now, if you're up in the chest, that's much more challenging. You're going to have patient positioning issues that you're not going to be able to do readily in the ICU. Obviously, if someone's dying and you need to do a crash sarcotomy, we can certainly, you know, we do that at the bedside all the time in the emergency department.  So, yeah, I think one of the things I would like, I would highlight is if you think you're encountering significant blood loss, get your perfusionist there. And the other thing to remember to have at the bedside is your whole array of topical hemostatics. You don't want to be saying, hey, get me, you know, the latest, greatest topical hemostatic and it's not there and the resident has to go run to the OR and bring it back.  So, yeah, you have to be kind of thinking a little bit ahead of time and always at the forefront of your mind is going to be hemostasis. And probably for a laparotomy, probably the thing that's going to give us the most problem at the bedside is if a patient is full of adhesions, then you're going to really need to be in the operating room.  Also, Mark, a comment that if you're on a bivalve infusion with the cell saver, you need to put citrate in it to prevent the cell saver.  Marie, what I would just add is we've done all our VV ECMO decannulations at the bedside, but we've had probably three VA ECMOs. We've taken those patients to the operating room just for more vascular like repair as necessary. It's just a lot easier now. We probably have three dedicated COVID ORs since probably the March of, you know, and so it's just become second nature now.  Good point. Better to be prepared than disappointed, I guess. We've got about five minutes left. Final pearls, final rabbit out of the hat you guys want to share?  Actually, Marie, we had this one question maybe we can go back to on stents and what to do. So I kind of put a little bit in there. The fact that with the stent, if it's a recent stent within the last month or two and such, we obviously have to protect the stent in the hospital.  And antiplatelet therapy is probably the preferred way to add to the regimen. So in such cases, obviously it increases the risk of bleeding. We tend to use tire fly band because it's short acting and it's a lot easier to manage these patients. And we published that experience. I put the reference in there.  But you do sometimes have to do that and manage these patients accordingly to protect the stent as well. And it's always important not to forget about the stent. Sometimes we get focused on all the other issues and we forget, oh, hey, by the way, there's a stent in place and we haven't done anything for it for several days.  So it's starting the therapy when you think it's safe to do so and sustaining it and always keep in mind the importance of protecting the stent, which sometimes depends on the location of the stent. And if it thrombosis, what would be the potential complications from it?  So then do you titrate with ACT, with TAG?  Well, we look at the tags. It's really hard. You can also do platelet mapping with the tags. So sometimes you can add that in to get an idea of the bigger picture with it. But it's not really as reliable as a test, but it gives you another piece of information that helps make good clinical decisions.  But again, it really depends on bringing in the people who place the stents and their concern for instant thrombosis as part of the picture too. There's no clear answer, but I think it's important to keep these items in mind.  We use the Tyre5 and without a bolus in the PCI settings. Obviously, these drives are bolused as well as an infusion. We feel that there's no active thrombosis issue happening at the moment. So we just start them on a continuous infusion depending on renal function. We make it simple. And we sometimes lower the dose because we're concerned of bleeding. It's really a lot of clinical gestalt and really bedside decisions about the entire patient.  Maria, I'm told that there was an audio glitch on the question on intracranial hemorrhage. So just to review that again. So this was the question with reference to a report from the Penn Group about a higher incidence of intracranial hemorrhage during COVID-VV ECMO and whether that led us to modifier anticoagulation targets.  It's interesting. We have not experienced a high rate of intracranial hemorrhages. We've had two in almost 50 cases now. The Penn Group reported four out of 10. Interestingly, they ran their PTT with a target in the 40 to 50 range. And so the intracranial hemorrhage group had a mean PTT of 50 compared to the low 40s and the non-patients who did not experience it.  So we have not, given our low overall incidence and the need for other indications with reference to systemic anticoagulation, we have not modified our targets, which are typically a PTT in the 50 to 60 range, typically.  Yeah, and I'll add to that too, is that you get a stroke and then you get a hemorrhagic conversion. So just stopping anticoagulation doesn't necessarily prevent the risk of having the combination of events leading to the hemorrhage too.  Final words, final thoughts? If it were easy, you'd do it in your garage. That's what I have to offer.  I think, again, I would echo, I think, one of the messages that I think we'd all sort of share with respect to the panel. These are tough cases. These cannot be managed with just an intensivist, just a surgeon, just a hematopathologist and a pharmacist.  This really does require multidisciplinary cooperation because you are constantly weighing the bleeding risk versus the thrombosis risk. And it's not a one size fits all formula. Every patient is a little bit different. And individual days can change. You know, Monday can be different than Thursday. So I think the multidisciplinary collaboration is imperative here.  And I'll add to that, that if you can think about some of these questions from this presentation in forethought and work as a group to come up with a plan before it happens, it always makes it easier when this unfolds in front of you, you have kind of an idea of a plan of how to approach it.  And I think one of the things that demonstrates cross fertilization is the pediatric VAD network, the action group, actually has a stroke prevention checklist that they've initiated and have been monitoring stroke outcomes in pediatric patients on ventricular assist devices.  And with paying attention to, you know, blood pressure and the subtle changes to the exam and the medication doses, they're working on reducing the incidence of stroke in association with those.  And I think that's probably one of the things that we should be doing with ECMO if we don't already as centers, but being proactive about monitoring and collectively thinking about the observations made with respect to the locations that we find so devastating.  Whether it's a stroke or whether it's a pulmonary hemorrhage or a GI bleed or an acubitus or a wound dehiscence. Yeah, it's the collective that probably is the better observer than an individual.  So with 20 seconds to go, we thank you for your attention. Stay safe, stay well, and good luck to all. Enjoy the rest of the meeting.  Can I add one more thing? For those of you, we use a novel format here with really answering as a group through the whole program. 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Video Summary

The video features a virtual panel discussion on the challenges of managing hematologic complications in patients on mechanical support devices like ECMO. The experts emphasize the importance of personalized treatment plans and multidisciplinary collaboration in this context. They discuss the use of heparin as the most common anticoagulant, but mention that some centers have started using direct thrombin inhibitors. The panel highlights the need for ongoing research and the lack of clear guidelines in anticoagulation management for ECMO patients. They also touch on the feasibility and safety of performing surgeries at the bedside in ECMO patients, with appropriate anticoagulation adjustments. The speakers stress the importance of monitoring and intervention to find a balance between bleeding and clotting risks. They also mention the use of viscoelastic testing and other laboratory assays for treatment decisions. The challenges of managing anticoagulation in patients with stents are also discussed. The panel briefly addresses the topic of intracranial hemorrhage and the need for ongoing monitoring and collaboration in managing these complex patients. The video concludes with a call for continued research and collaboration to enhance outcomes for ECMO patients.

Asset Subtitle

Hematology, Procedures, 2021

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2021 Critical Care Congress held virtually from January 31-February 12, 2021.

Learning Objectives

Recognize key dilemmas in balancing anticoagulation and bleeding risk in patients on mechanical circulatory support
Weigh therapeutic options when dilemmas occur
Assess different perspectives in management and treatment among various disciplines

Case Presentation
Marie E. Steiner

Panel Discussion: Intensivist's Perspective
Subhasis Chatterjee

Panel Discussion: Surgeon's Perspective
Mark D. Cipolle

Panel Discussion: Pharmacist Perspective
William E. Dager

Case Presentation 1 Wrap-Up
Marie E Steine

Case Presentation 2
Marie E Steiner

Case Presentation 2: Intensivist's Perspective
Subhasis Chatterjee

Case Presentation 2: Surgeon's Perspective
Mark D. Cipolle

Case Presentation 2: Pharmacist's Perspective
Matthew R Wanek

Case Presentation 2: Wrap-Up
Marie E Steiner

Meta Tag

Content Type Presentation

Knowledge Area Hematology

Knowledge Area Procedures

Knowledge Level Advanced

Learning Pathway Skills and Procedures

Membership Level Select

Tag Anticoagulation

Tag Extracorporeal Membrane Oxygenation ECMO

Tag Surgery

Year 2021

Keywords

hematologic complications

mechanical support devices

ECMO

personalized treatment plans

multidisciplinary collaboration

heparin

direct thrombin inhibitors

anticoagulation management

ongoing research

bedside surgeries

anticoagulation adjustments

monitoring and intervention

viscoelastic testing

patients with stents

intracranial hemorrhage

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