SCCM Resource Library-Thromboembolic Disease: Can Accurate Diagnosis Inform Better Treatments? (Flipped Classroom)

Video Transcription

Good morning. My name is Sophia Chu Rogers. I'm a critical care nurse practitioner with the Lovelace Medical Group, Division of Pulmonary and Critical Care.  I'm going to be the moderator for this session titled, Thromboembolic Disease, Can Accurate Diagnosis Inform Better Treatments? I have no disclosures.  So this session is in a flipped classroom format. And for those of you who may not be familiar with this, this is a very interactive format that involves audience participation.  Beforehand, we posted some articles and links, and you will find these in the session. When you click on a little file button, the articles will be there.  Hopefully you've had a chance to look through these prior to attending the session. The articles are meant to augment the topic which we will be discussing.  Also throughout both presentations, there are going to be poll questions. They're going to come up.  There's going to be an instructional slide to show you how to access the questions, and you can answer them with your smartphone.  Also throughout the presentations, please feel free to ask questions through the live chat. We will answer these questions at the end of both presentations. Okay.  So without further ado, let's talk about the first topic. This is presented by Dr. Alekouli Aydogu, and he is going to talk about measuring coagulations,  where and when does TAG fit in with classical app essay. I'm going to stop share while he logs on, and let me make his introduction. You can go ahead and log on, Dr. Aydogu.  So Dr. Aydogu is an assistant professor in the Department of Anesthesia and Critical Care Pain Medicine at MD Anderson. He's board certified in anesthesia and critical care.  After graduating from the University of Maryland, he earned his medical degree from Virginia Commonwealth University.  He attended SUNY Downstate in Brooklyn, New York for his anesthesia residency and received his fellowship in critical care at University of Texas in Houston.  Following his fellowship, he went into private practice before becoming faculty at MD Anderson.  He is an active member of the American Society of Anesthesia and the Society of Critical Care Medicine. In 2018, he was awarded the Presidential Citation by SCCM.  He's also certified in medical quality. He has served as a fundamental and critical care support instructor, and he holds the  testimony status for critical care through the National Board of Echocardiography. His academic interests include thoracic anesthesia, trainee education, and quality improvement.  Please help me welcome Dr. Aydogu. Thank you for a wonderful introduction, and hello, everybody. As she mentioned, I'm Olukunle Aydogu, an assistant professor of anesthesiology and  critical care at UT MD Anderson Cancer Center in Houston, Texas. I have no disclosures. Today, we will define the challenges in the diagnosis of thromboembolic disease and critical  illness, and we'll also review the measurements of coagulation through thromboelastography, rotational thromboelastometry, anti-TENA, and classic hematologic laboratory assays.  So thromboembolic disease in a critically ill, why should we care? Well, it's one of the most common, often preventable causes of death in the hospital, and it tends  to be a blind spot for clinicians, because one of the biggest challenges is identifying asymptomatic patients, which is estimated at roughly 10%.  I actually suspect that this number is greater, and this is an underestimation. So 10% to 30% of patients with VTE die within 30 days, and survivors end up being at risk  for reoccurrence and chronic syndrome, such as post-thrombotic syndrome and chronic thrombotic pulmonary hypertension.  As you can expect, there's a big price tag associated with this. And for most critically ill patients, there are a lot of risk factors, most notable obesity and vasopressor use.  So the American Society of Hematology has equipped us with guidelines for PE and VTE diagnosis. So the first thing you have to do is determine your pretest probability.  So for PE, you can use your WELL score or revised GENEVA score. And for lower extremity DVT and upper extremity DVT, you can use your WELL score or constant  STOOK score, respectively. You combine this with a diagnostic modality, CT, pulmonary angiography, D-dimer, ultrasound, or VQ scan to determine your post-test probability.  Please note that these tests have differences in their sensitivity and specificity. Some tests are both sensitive and specific, whereas others are sensitive versus specific.  So in terms of diagnosis, as I mentioned, you want to get your pretest probability using  your screening tool plus your diagnostic modality should give you your post-test probability. The problem is that this is the best available, but it's not always reliable.  We have all experienced the patient who's too unstable to transport for CT, pulmonary angiography, or has impaired renal function, causing us to use other diagnostic tests  or surrogates to determine the likelihood of thromboembolic disease. So no test is perfect.  Therefore, the biggest tool we have as clinicians is to focus on prevention and initiate an appropriate VTE prophylaxis. So how are we doing in that regard?  Well, this was a large multinational cross-sectional study that found that only 58.5% of surgical patients and 39.5% of medical patients received appropriate VTE prophylaxis.  This study included 32 countries with just under 70,000 patients. So it just essentially shows that there's a lot of room for improvement, and this is a global issue.  This is how we currently understand hemostasis. This is a model that has been long used and has been taught in all pretty much health  professions to understand both the intrinsic and extrinsic pathway and how we obtain hemostasis.  So we understand that there are several limitations to this model, and we know that through research,  that in vivo and in vitro models do not correlate well.  For example, factor XII deficiency plays a minor role in the coagulation cascade, as you  know that an elevated PTT from a factor XII deficiency does not correlate with bleeding.  This model also disregards the link between primary and secondary hemostasis, and then we also now understand that newer models incorporate leukocyte activation versus  vascular damage, which is seen in COVID-associated coagulopathy.  So how do we use laboratory tests to determine coagulation states?  Prothrombin time is what we typically use to understand the activity of the extrinsic and common pathway, and we also use it to derive our INR. Activated partial thermoplast in time  allows us to assess intrinsic pathway activity as well as the common pathway.  And then you have thrombin time, which tells us about the time necessary for thrombin to convert  fibrinogen to fibrin. Platelet count and fibrinogen count give you a number. They may not necessarily  tell you about function, and then you have fibrin degradation products, which can be a marker of  increased fibrinolysis. The last two mentioned here are your antithrombin III levels, which can  be helpful in understanding heparin resistance, and your anti-TENA levels, which are typically used to assess intrinsic pathway activity and to monitor the activity of coagulants.  So some limitations of these standard laboratory tests. Most, if not all of them, are an assessment  of plasma, not whole blood. They typically provide no information about clock quality,  platelet function, or the extent of fibrinolysis. And as I mentioned, numbers do not equal function.  There's a difference between quantitative and qualitative function. These samples are typically temperature corrected and run at 37 degrees versus the actual patient temperature,  which for patients who have states of hypothermia and acidosis, there is a limitation in understanding what's actually going on. And then you can have falsely elevated labs,  and especially in the case of an elevated PT and activated partial thermoplast in time with  hyperfibrinogenemia. So the most common complaint we all have with standard laboratory tests are the longer result times. And this is something that point-of-care testing has  addressed to some extent, but some of these labs cannot be obtained by point-of-care testing.  So viscoelastic testing provides information about clock quality, stability, coagulation factors, and can reveal information about both hypocoagulable and hypercoagulable states.  So who do we owe this honor? To Dr. Helmut Hartert. He was a German scientist and physician who is responsible for publishing on thromboelastography in 1948. He also has several  other notable inventions and contributions to science. So what is a viscoelastic assay?  It provides a functional assessment of whole blood clot formation in a low-shear environment.  The two most common devices on the market are TEG and Rotem. TEG was approved by the FDA in the year 2000 and Rotem in 2010. Both devices have assays or tests that you can run to  delineate a specific platelet or fibrinogen function. And there are also newer models  or newer viscoelastic assays, which actually use ultrasound technology  and can serve as point-of-care devices. So what does it tell us specifically  when you look at the results? So in the case of either vascular injury or endothelial activation,  you can understand the time from that point to clot formation, which can give you information  about factor deficiencies. You can also understand about the kinetics of clot formation through the  alpha angle and K time. And that tells you how both fibrin and platelets are starting to interact.  And then you can also understand information about the maximum clot strength, which 80% of it is  typically provided by your platelet activity. And again, this still goes back to platelet and  fibrin cross-linking. And then lastly, it can tell you about fibrinolysis, which is also  a very important part of hemostasis. So most of TEG interpretation is pattern recognition. I'll  just review a few here. As you can see, this is a patient with a prolonged R time, a decreased angle,  increased K time, and a decreased MA, representing likely a factor deficiency, and potentially also a platelet deficiency. And this is a picture here showing you a patient,  both an early and late DIC. As you can see, the hypercoagulable state here. And after the patient  experiences a consumption of factors with increased fibrinolysis, you can see that the TEG thing thins out. So how has TEG been used to assist with the dosing of thermoprophylaxis?  This is a study that was published in 2016. It was a randomized controlled trial. Unfortunately,  they were not able to show that TEG helped them adjust the dosing of noxipirin for thermoprophylaxis.  But they did find, which is, I think, very important information in antithrombin 3 deficiencies  and also hypercoagulable TEG parameters were prevalent among patients with VTE.  So in summary, critically ill patients are at high risk for thromboembolic disease. And I showed you several risk factors. Again, most notably, obesity and vasopressor use  have been described in the literature. Diagnosis remains a challenge. And it's always difficult to  pick up asymptomatic patients. Currently, the guidelines from several societies do not recommend  routine testing of every critically ill patient for thromboembolic disease. Compliance with DVT  prophylaxis is lacking across the board. And this is a global issue. Depictions of intrinsic and  extrinsic coagulation pathways have limitations. As I mentioned, in vivo and in vitro models do not  correlate. And newer models actually describe leukocyte activation as what we're dealing with  with the COVID-19 pandemic. Standard laboratory tests provide assessments of coagulation through  spun plasma, not whole blood. And then the link between primary and secondary hemostasis is not provided in one test, which is an issue that viscoelastic testing does address.  And then, of course, the longer processing times.  So we'll go into a case for further discussion. So this is a 58-year-old male with a history of  hepatocellular carcinoma, started post-left hepatectomy with significant intraoperative  blood loss and coagulopathy noted during provider handoff in the ICU. Patient is intubated and  sedated. And his drains have mostly sanguiness or bloody output. You can see here that intraoperative  blood loss was 1.2 liters. He was transfused several units of blood products. And you can  see that he has kind of what you see would be marginal hemodynamics here with some hypothermia.  As expected, your first set of labs come back 45 minutes after arrival to the ICU. And I'll just give you a second to take a look at these laboratory values.  So the first question is, what should you do first? A, transfuse packed red blood cells. B, transfuse cryoprecipitate. C, transfuse FFP. D, transfuse platelets. E, call the surgeon.  D, transfuse the blood. And finally, B, transfuse the blood.  F, transfuse FFP. D, transfuse platelets. E, call the surgeon. We need a return to OR  to correct surgical bleeding. Or F, I need more information.  Please follow the polling instructions to submit your response to this poll.  It looks like most of us, if not all, I think it looks like all of us have chosen F. Yes,  I agree. This is a situation where we need more information. I would like to know whether this is  surgical bleeding or coagulopathy. Coagulopathy is something as a clinician that I could  address at the bedside. But I need to definitely address that first before returning to the OR  to correct any potential surgical bleeding. Any return to the OR has its own inherent risk.  So, the next question is, which test will you use to determine surgical bleeding versus coagulopathy?  A, you would repeat your standard laboratory tests. B, you would order a viscoelastic assay. C, you would order an anti-10A level.  D, you would order an antithermin 3 level. Or E, you would order an ACT.  So in this scenario, you can repeat your standard laboratory test, but you're most likely going to get the same or similar information.  A viscoelastic assay would be helpful because it gives you a real time depiction of what's happening with whole blood. Again, this patient was hypothermic.  So that's another consideration is that a viscoelastic assay would actually give you a depiction of this patient's whole blood clot formation or how this patient is clotting given the hypothermia and what other factor deficiencies he may have.  Anti-TENA levels would be more helpful as well as an ACT if this patient had received heparin. Again, this information would give you just a very small part of the picture, but would not be a comprehensive assessment of this patient's coagulation status.  So because we decided to order a viscoelastic assay, we ordered a TEG, and these are the results both with and without heparinase. Just keep in mind, this patient did not receive heparin intraoperatively.  So I just want to give you a second to think about what these TEG parameters tell you about factor deficiencies, what they tell you about platelets, about fibrinolysis, and the risk of hemorrhage or thrombosis.  So just as you're looking through it, generally speaking, R-TIME is helpful in understanding coagulation factor deficiencies. Both K-TIME and ANGLE are important in understanding fibrinogen deficiencies as well as the kinetics of clot formation.  Your maximum amplitude is typically helpful in understanding mostly your platelet activity. As I said, roughly 80% of it comes from your platelet activity. And then your G-VALUE is an overall assessment of clotting.  And generally speaking, of G-VALUE less than 5, patients are more prone to hemorrhage and greater than 10 more prone to thrombosis. Expected percent lysis tells you about the extent of fibrinolysis.  And then a coagulation index gives you similar information in terms of the G-VALUE where it's less than negative 3. Patients are more prone to bleeding and greater than 3, they're more prone to thrombosis.  So in this patient, what is the issue? A, they have a hypercoagulable state. B, they have platelet and coagulation factor deficiencies. C, they have their experience in secondary fibrinolysis. D, they're showing a heparin effect. E, they're in DIC, early DIC, or F, in late DIC.  So, based on the tag, this patient actually has platelet and coagulation factor deficient of coagulation factor deficiency.  And I know that because the R time is prolonged and the patient also has a decreased MA, I do factor in the fact that this patient has an increased K time, slightly increased K  time and decreased angle, but this can potentially be corrected by either giving platelets and correcting the coagulation factor deficiency with FFP.  Okay, I see we're kind of split across the board here. For dissipation, I would give A, FFP. FFP would be the first product of choice.  Typically, when you are correcting the tag, if you have a prolonged R time, it's better to correct the coagulation factor deficiencies, as I just mentioned.  When you do that, you can see a change in both your alpha angle and K time, which may correlate to a slightly improve or improvement in your MA.  But you can definitely give FFP first and then reassess for the need to give platelets. In this scenario, cryoprecipitate, at least at this point, is not indicated.  One benefit is that you have standard laboratory tests. You have a fibrinogen level of 175, so it's unlikely that that is, per se, the issue at this point.  Of course, if your repeat labs are different, then you can factor into your decision. And then the last question is, when would you start pharmacologic DVT prophylaxis?  Okay, just for the sake of time and consideration of time, the answer here is C. I would repeat a tag in standard laboratory tests after transfusions to determine.  It may sound counterintuitive, but if you remember early in my discussion or in my talk that antithrombin 3 deficiencies are prevalent in patients who have or fail pharmacologic  DVT prophylaxis and end up with thromboembolic disease. So in this patient, prior to starting DVT prophylaxis, I would still correct with FFP and potentially platelets.  I would repeat the labs just to make sure that the patient with the other tag parameters  is not more prone to hemorrhage or bleeding, and then I would start DVT prophylaxis potentially even the same day, depending on what I say.  Thank you all, and I'm happy to entertain any questions. Okay, I am going to go ahead and introduce our next speaker, and as questions are coming  in, I will let you guys know at the end. Our next topic is going to be presented by Dr. Van Cleave. He is going to talk about case-based treatment guidelines.  How does this apply to my patient and clinical scenario? Dr. Van Cleave is a critical care clinical pharmacist at Lovelace Medical Center.  After graduation from the University of Tennessee College of Pharmacy, he completed his training  with a PGY-1 in pharmacy practice at the Memphis VA Medical Center and PGY-2 in critical care at Regional One Health University of Tennessee.  Dr. Van Cleave currently practices in a mixed surgical medical ICU at Lovelace Medical Center in Albuquerque, New Mexico.  He's also a preceptor for a PGY-1 pharmacy practice residency and a clinical assistant professor at the University of New Mexico College of Pharmacy.  His areas of expertise include acute respiratory distress syndrome, anticoagulation, and infectious disease. Please help me welcome Dr. Jonathan Van Cleave. Good morning.  Thank you for that introduction, Sophia. So today I want to talk about case-based treatment guidelines. How does this apply to my patient and clinical scenario?  As Sophia said, my name is Jonathan Van Cleave. I'm a clinical pharmacist at Lovelace Medical Center in Albuquerque, New Mexico.  I have nothing to disclose for this presentation today. For my objectives today, I wanted to talk about review the pharmacological treatment  options for venous thromboembolism disease through cases. Like Sophia said, this is a flipped classroom, and so there was pre-reading, and so I will  refer to that as I go through my presentation. The second objective, I want to discuss how laboratory assays can be used to monitor and  adjust pharmacological treatment plans for VTE, and specifically I'm focusing on treatment today. I want to start off with unfractionated heparin.  It's ski season out here in New Mexico, so if you can see over on the right, I have our green, which should mean that most people should be able to use this drug and know about it.  It's the workhorse of our anticoagulants in the ICU. Its mechanism inactivates thrombin and prevents conversion of fibrinogen to fibrin.  You're going to give a bolus followed by continuous infusion. For monitoring, you can either use anti-factor 10A or APTT, and we'll get more into that in just a second.  Elimination is through the reticuloendothelial system with some renal clearance. For reversal, it can be reliably reversed with protamine sulfate.  Some advantages, you can use it in renal failure. It does have a short half-life, and it can be easily reversed.  Some disadvantages, it does require intensive monitoring, and there is the risk of hit. I put 3% on this slide, however, it depends on your population on how high this is with  surgical being much higher than medical ICU patients. Going into the monitoring, which I just mentioned, you can use APTT or you can use anti-10A.  This is a study back from 2011 looking at the differences between these. Basically, what they were looking at was how quickly you became therapeutic within the  first 24 hours when using different laboratory assays. As you can see, a majority of patients were either sub-therapeutic or super-therapeutic when using APTT.  However, a much larger patient population was able to be therapeutic within the first 24 hours with using anti-10A.  There's a few different things that can affect APTT and why it makes it not the best lab assay to use to monitor. Dr. Odawu mentioned factor deficiencies being one of them.  Also COVID-19, warfarin, different antihistamines can affect it. There's many different factors besides the actual drug that is making APT not the best laboratory assay.  Also, it does not pick up with all the adjustments in dosing as well. Most laboratories in the US, I think, are still using APTT, but as more information  comes out with anti-10A, I think this is going to be the more preferred approach going forward.  Our next drug group that we're going to talk about is enoxaparin and daltaparin, which are your low molecular weight heparins.  These work by inhibiting factor 10A, and they do have also some antithrombin activity. Dosing there is as follows.  I want to point out that the 1.5 mg per kg once a day is not approved for pulmonary embolism.  Now monitoring is recommended in certain populations, so pregnancy and obesity, and we could probably actually add COVID-19 to this group as well.  Now looking at monitoring, it's considered therapeutic if you're between 0.5 and 1, and prophylaxis is 0.2 to 0.5.  Now the elimination is highly dependent on renal function, and most references will recommend avoiding it with a creatinine clearance less than 30 mls per minute.  Now for reversal, you can use protein sulfate, however, this is only a partial reversal.  Some advantages of using this drug is there's a much lower risk of hit than with unfractionated heparin, as low as 0.2%.  It's easier for your nursing staff to administer, and it's possibly more effective than unfractionated heparin.  Some disadvantages, there is a black box warning for epidural hematoma, and like I said earlier, it can accumulate with renal failure.  Now ifondoparanux is also another green drug that you should be familiar with. This is a selective inhibitor of factor Xa. Dosing depends on the weight.  You can use anti-factor Xa to monitor, however, your laboratory assay must be specifically calibrated for this drug.  For elimination, it's renal and is contraindicated with creatinine clearance less than 30 mls per minute, so similar to your low molecular weight heparins.  Some advantages, it can be used in HIT, and there is once-daily dosing, which makes it easier to administer.  Some disadvantages, it is expensive, with a month's supply costing several thousand dollars, and there's that accumulation in renal failure.  Next we have our gatcher band, which we're moving more to the harder-to-use drugs, so I put blue here for this one. This is a direct, highly selective thrombin inhibitor.  Now I put the normal dosing range that you would use initially, however, there's more literature coming out that we actually should probably be using lower dosing ranges, and  that's due to a few different factors. Critically ill patients metabolize and have a different volume of distribution for this drug.  It's also hepatically eliminated, so for your patients with severe hepatic disease, you would need a lower dose.  So what most places are recommending now is to start out with 0.2 mcs per kilo per minute. Some advantages for this drug, it can be used in HIT, it can also be used in renal  failure, and it's short-acting. Some disadvantages, it requires intensive monitoring, similar to Heparin drip.  It's expensive, this is also several thousand dollars for a treatment course over several weeks, and it's hard to transition from our gatcher band to Warfarin.  Moving into one of our more difficult drugs, I put expert only as a black double diamond for this one, is Bivalarutin.  Now many people have more experience with this in the cardiac ICU population, however, it can be used in the medical ICU.  It is a direct thrombin inhibitor, dosing you want to initiate at 0.2 mcs per kilo per hour.  You're going to use monitoring based on APTT, adjusting it to a 1.5 to 2.5 times the baseline. Transmission is renal, it can be used in HIT, and it's short-acting.  Some disadvantages, it's expensive, and most clinicians lack experience using this drug. Going into our tried and true oral anticoagulant that we've had for several decades now, we  have Warfarin or Coumadin. This is a vitamin K inhibitor, which affects clotting factors 2, 7, 9, and 10.  The dosing is widely variable depending on which patient you're using it in, and you're going to adjust based on an INR. Elimination is hepatic through the CYP450 system.  Reversal, you would use vitamin K in a four-factor prothrombin complex concentrate. The only available one that we have here in the United States is Kcentra.  Some advantages, you can use it in renal failure. We have many years of experience and lots of literature on this drug, and it does have a reliable reversal.  Some disadvantages, it requires monitoring as an outpatient, which is the reason why a lot of places have transitioned to DOACs.  It initially causes a hypercoagulable state, which is not advantageous for somebody who has an active clot, and it does have a long, effective half-life, inhibiting the clotting  factors for several days. Going into our newer oral anticoagulants, we have our oral factor Xa inhibitors.  We have rivaroxaban, epixaban, and doxaban, which are the ones that are approved for treatment of VTE.  You can monitor these with an anti-factor Xa, however, there's not generally agreed upon what is considered therapeutic for these drugs, and your laboratory assays have to  be calibrated specifically for these agents. You can't use the anti-factor Xa levels, for example, that are used for heparin or ovinox.  Elimination is mainly renal, with some hepatic elimination. Reversal is usually institution-dependent.  I will say that the only FDA-approved reversal agent for these drugs is indexinet-alpha, but many institutions are using your four-factor prothrombin complex concentrates.  Some advantages is fast onset. There's no monitoring required, which can be an advantage or a disadvantage, depending  if your patient's bleeding or you're wondering about the anticoagulant effect. There are less food and drug interactions than warfarin, which makes these a little bit better.  Some disadvantages is accumulation of renal or hepatic failure. They are more expensive, and they do have an expensive reversal, especially if you're using indexinet-alpha.  Our last oral anticoagulant that I wanted to discuss today is the Bigotran or Pradaxa. This is probably the least used of the oral anticoagulants.  This is a direct thrombin inhibitor. For lab monitoring, you would use a dilute thrombin time. It has a specific reversal, which is Prax-Bind, which is specific for this drug.  Its elimination is hepatic and renal. Some advantages, it does have a proven reversal agent. There's no outpatient monitoring required.  However, disadvantages, similar to the other DOACs, is there's accumulation of renal and hepatic failure.  Going into our cases, which is where I want to spend a good bit of time working through this, as this is a flipped classroom format. Today we have a 45-year-old male.  He's admitted to ICU for shortness of breath and chest pain. CT angiography reveals a saddle pulmonary embolism due to significant hypotension and elevated troponin.  The patient was treated with alteplase IV, 100 milligrams over two hours. How should this patient be managed going forward? So I'll give you a second to kind of look through that.  So which anticoagulant would be most appropriate for this patient post thrombolysis?  So our options that we have are inoxafarin, warfarin, unfractionated heparin, continuous infusion, or ribaroxamine.  So for the sake of time, I'm gonna start moving through these. So for example, inoxaparin, we could use this and actually some of the studies have used full dose inoxaparin.  However, as we mentioned earlier, inoxaparin does stay around for a long period of time.  And thrombolysis does carry a risk of intracranial hemorrhage around two to 5%. So you would not want a patient to have intracranial hemorrhage  and then you would have to reverse them. And remember inoxaparin is only partially reversible. So it's half-life and its ability to only be partially reversed  kind of works against us in this situation. Warfarin would be a good long-term option. However, remember this does last several days with its effect on this clotting factors.  So this would also not be a good option immediately post thrombolysis.  The correct answer is unfractionated heparin, continuous infusion. Remember it has a quick onset and it has a decently quick offset,  but it's also able to be completely reversed with protamine. The other one is rivaroxaban. If you did have an ICH, you would be dealing with a very expensive reversal  if you use this immediately post thrombolysis. So unfractionated heparin is the correct answer for this one. Going on to our second question,  which lab parameter would be most helpful to decide when it is appropriate to start post thrombolytic anticoagulation? And this goes a little bit  into Dr. Dawood's presentation on laboratory assays, but this was in the pre-session reading.  So our options here, we have APTT, INR, prothrombin time, and fibrinogen.  So on this question, there's actually a couple of different correct answers and I would probably actually send two of these laboratory assays.  So as you can see that a majority of people actually put APTT. Now I would, in our practice, we use this to measure the effect of alteplase post thrombolysis.  So you would wait about two hours and then you would check an APTT. With a half-life of alteplase, it should be gone by then. But what you're looking for is an APTT  less than two times normal or less than 80 is what we are using. Now fibrinogen is another lab I would send. So a fibrinogen less than 150, for example,  would be predictable for whether this patient is at risk for further bleeding. So we actually send both of these typically post thrombolysis.  Going on to our next question, what lab parameter would be most appropriate  to monitor the heparin drip? Now we discussed this a lot earlier, so I would assume a majority of you would get this one.  So for our answers, we have INR, anti-factor 10A level, APTT, and prothrombin time.  So, looking at our answers here, anti-factor 10A level would be the most appropriate. Like we were talking about earlier, it is much more specific and does not have as many  factors that affect the levels as a PTT. So for this patient, we would use an anti-factor 10A level. Going on to our next question.  On day two of admission, the patient's hypotension has resolved and signs or symptoms of bleeding are seen. Which anticoagulant would be most appropriate to transition to?  For our answers, we have enoxaparin, rivaroxaban, warfarin, or epixaban. Now for this question, I put several correct answers.  You could technically transition to any of these agents. Enoxaparin would work. However, if you're going to be sending the patient home, it would require them to be  able to give themselves injections. If you were using warfarin, you would have to probably use a combined strategy of a bridge with enoxaparin and warfarin.  If you're using rivaroxaban or epixaban, you could send them home immediately without a bridge.  So going in to the CHESS guidelines, they now recommend using the newer anticoagulants such as vigatran, rivaroxaban, epixaban, or doxaban.  So the most correct answer on this would be rivaroxaban or epixaban. Going into our next case, a 58-year-old man is admitted to the ICU with septic shock from  pneumonia and had a decrease in platelet count from 180,000 on day one to 65,000 on day eight.  He has been receiving DBT prophylaxis with unfractionated heparin, 5,000 units Q8, since admission due to acute renal failure.  Also note lower extremity Doppler's reveal femoral DBT. How should this case be evaluated and treated?  So looking for heparin-induced thrombocytopenia, we would first want to do a 4T score. So this patient would get two points for the timing.  It would get two points for the acute thrombocytopenia. It would get two points for the new thrombosis.  However, with the other cause of thrombocytopenia, the patient did have sepsis, so it does have another reason for the patient to be thrombocytopenic.  So going into our first question, what should your initial workup include? Should you start a heparin antibody test and serotonin release assay?  Should you switch to low molecular weight heparin? Should you stop all the heparin products, order a heparin antibody test and serotonin release assay?  Or should you stop all heparin products, order the heparin antibody test and serotonin release assay, and start a non-heparin anticoagulant?  So looking through these, it looks like we're kind of evenly split between B and D. Seeing  that this patient has a higher risk on the 4T score, we would both want to stop the heparin products, order the test.  We typically order these both at the same time because there can be a delay in the serotonin release assay, and then start a non-heparin anticoagulant.  So D would be the correct answer. Now going through the HIT guidelines, if you can see, we are moving down to the left side of this flowchart.  So the 4T score would be greater than or equal to 4, and so we would discontinue heparin and start a non-heparin anticoagulant, and then you would obtain the immunoassay.  Going into our next question, which anticoagulant should we start with?  We have A. Fondoperinux, B. Argatroban, C. Bivalarudin, or D. Warfarin. Now I didn't mention the renal function on this patient, so there is a little bit of a lack of information.  So it looks like we have a good bit of people saying Argatroban. So we could actually use the first three on these answers. We could use Fondoperinux.  It would be easier to administer. We could use Argatroban as well if the patient, for example, had renal failure.  We could use Bivalarudin, however, there isn't a lot of experience using this drug in the majority of ICUs.  Warfarin would be the one that I would want to avoid as the platelets have not recovered. After four days of treatment, platelet function has recovered to 150,000.  The patient's renal function has recovered, creatinine clearance at 90 mL per minute, and the patient is appropriate for discharge.  What agent is most appropriate for treating the patient going home? So A, we have Fondoperinux. B, we have Warfarin. C, we have Apixaban. And D, we have Enoxaparin.  So looking through these, we could send the patient home on Fondoperinux. However, that would be very expensive.  We could send the patient home on Warfarin, as the platelets have now recovered. We could send the patient home on Apixaban as well.  So the HIT guidelines actually recommend to use Rivaroxaban or Apixaban if we're going to use a direct oral anticoagulant.  So probably, actually, I would send the patient home on Apixaban. However, you could also send the patient home on Rivaroxaban.  If cost or insurance is an issue and the patient's insurance wasn't covered, you could send the patient home on Warfarin. The only one I would not use would be Enoxaparin.  And how long should the patient be treated for heparin-induced thrombocytopenia? Should you treat the patient for one month, three months, one year, or indefinitely?  See, we have a couple answers coming in with B, three months.  So, in these patients, you treat these basically like a provoked clot. So, the guidelines recommend that you treat for a minimum of three months  up to six months, similar to a provoked clot.  So, B would be the correct answer. And if there's any questions, you can always feel free to email me  or put your polling questions, and Sophia will be moderating our questions portion.  And I do have questions. This one's for you, Dr. Finkley. The question is, when do you recommend monitoring the anti-TNA assays  for factor TNA inhibitors?  That is actually a really difficult question. We do not traditionally monitor them as, for example, on admission.  However, we sometimes do send one to see if they are anti-coagulated. The difficult portion of that is telling what is considered a therapeutic level  of factor TNA inhibitors, especially when we're looking at the oral ones. Another difficult portion is, if they come in on one,  it can actually affect your heparin factor TNA assay as well, even after the drug is out of the system.  So, we typically only check it if we're trying to decide if the patient is actually on it at home or not.  Our ICU patients, a lot of times, we don't get the best history in the world. So, sometimes we do check that.  But that's an area, actually, for a lot of further research is telling what level of factor TNA is equivalent to what level of anti-coagulation, at least on the inpatient side.  It would also help with reversal as well. So, I think it's an area for further research.  Okay. Dr. Daidau, this question is for you. Are there certain patient populations that it would be more prudent to use tests other  than the TAG, such as using D-dimer to exclude the VTE? That's part one of the question. Part two is, what is the cost associated with using TAG and Rotam compared  to your standardized lab tests?  Okay. Can you just repeat the first part of the question again? Sure. What, what, hang on, the question's just changed. Hang on, let me find it.  Oh, are there certain patient population that it would be more prudent to use tests other than TAG, such as using D-dimer to exclude VTE?  Yes, absolutely. So, if you, and I provided ASH, Society of, American Society of Hematology guidelines.  And if you go through the guidelines, they tell you, based on your suspicion of the presence of thromboembolic disease, you, what tests you can order.  So, for instance, if you have a very low suspicion in that patient, you should start with a D-dimer.  Versus escalating to getting a CT, pulmonary angiography, or getting low extremity diapers. The first test you should order is a D-dimer, because if the D-dimer is negative,  and you have a low suspicion that the patient has thrombo, venous thromboembolism, of venous thromboembolic disease, then you can stop the workup right there.  And that's in the guidelines, pretty much verbatim. Now, where TEG comes in, is that it's not ready for prime time in the sense  where you should use it to guide your, as I mentioned in the presentation, guide your VTE prophylaxis.  It's more so available now for you to assess the patients who are at risk for hemorrhage or thrombosis. So, the last question, poll question I had, is probably the most critical.  So, you have a patient where your standard laboratory tests don't give you a clear picture about what's going on, and you know that that patient population,  specific patient population, is at high risk for thromboembolic events. Then, ordering a TEG can let you know, well, this patient has an elevated MA, a short R time,  and you can see all the different parameters and use that to make a better clinical decision. So, it should not replace your standard laboratory tests at this point,  just kind of along the lines of how anti-TENE levels have not replaced PTT. I'm just drawing a parallel here.  But I think in the future, as we use TEG more, as more point-of-care devices come on the market  with more specific platelet and fibrinogen mapping, it will be more useful to make assessments. But please refer to the ASH guidelines for a step-wise approach to  determining which diagnostic test you should order.  And what's the cost?  So, I can't quote the cost because there are new devices on the market,  and it depends on the lab, but it is significantly more, I do know it's significantly more expensive than ordering, let's say, a PTT.  A lot of institutions may not have TEG, or if they have a TEG or Rotem,  you know, like, for instance, my institution, we have a TEG 5000, as I mentioned.  There are several new devices on the market. There's a RapidTEG.  There's a TEG 6S Sonoclot, which is used in Europe. Rotem has different assays that they've introduced to give you specific information.  So, they're, I'm sorry, I can't quote you a specific number, but it is more expensive, which has probably been the major reason for, in terms of adoption,  of using TEGs as a routine or standard of care. Since you mentioned the TEG 6, there was a question, is TEG 6 superior to a regular TEG?  So, TEG 6S starts to fall into the category of point-of-care or RapidTEG, or, well, point-of-care testing. TEG 6S, so there's RapidTEG, which just uses tissue factor,  as a reagent, to speed up the reaction, so you get the information faster.  You'll find 6 RapidTEG in a lot of trauma bays,  but specifically 6S is using ultrasound, uses ultrasound-based technology, which is similar to a device called Quantra.  We've actually tested the Quantra here at our institution, in the operating room, and both devices give you,  they're apples to oranges in terms of the parameters. They're giving you similar information, but the parameters are not the same. They're not interchangeable.  I hope I answered your question.  Our time, unfortunately, is up.  That was excellent. We still have several other questions. I would suggest that those of you, Dr. Aido and Dr. Van Cleve, have given you their email.  Please feel free to email them your questions, so they could answer you personally. I want to thank all of you for attending our session,  and thank our two speakers for doing an excellent job on this topic. Thank you very much, and enjoy the rest of the conference.  Thank you.

Video Summary

The session titled "Thromboembolic Disease: Can Accurate Diagnosis Inform Better Treatments?" was moderated by Sophia Chu Rogers, a critical care nurse practitioner. The session was conducted in a flipped classroom format, with pre-reading materials provided for attendees to review before the session. The session focused on the challenges in diagnosing thromboembolic disease and reviewed various laboratory assays that can be used to determine coagulation states. Dr. Olukunle Aydogu presented on the use of thromboelastography (TEG) and other laboratory assays in diagnosing and monitoring thromboembolic disease. He discussed the limitations of standard laboratory tests and the advantages of viscoelastic testing. Dr. Jonathan Van Cleave then presented case-based treatment guidelines and discussed the appropriate use of anticoagulants in specific patient scenarios. He highlighted the importance of monitoring and adjusting pharmacological treatment plans and discussed the advantages and disadvantages of different anticoagulant options. Overall, the session provided valuable insights into the diagnosis and treatment of thromboembolic disease in critically ill patients.

Asset Subtitle

Hematology, 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

Define challenges in the diagnosis of thromboembolic disease in critical illness
Review measurement of coagulation through thromboelastography, rotational thromboelastometry, anti-Xa, and classic hematologic laboratory assays
Review pharmacologic treatment options for venous thromboembolism disease through cases

Measuring Coagulation: Where and When Does TEG Fit in With Classic Laboratory Assays?
Olakunle Idowu

Case-Based Treatment Guidelines: How Does This Apply to My Patient and Clinical Scenario?
Jonathan Van Cleve

Challenging Cases in Hemostasis
All Faculty

Meta Tag

Content Type Presentation

Knowledge Area Hematology

Knowledge Level Intermediate

Knowledge Level Advanced

Membership Level Select

Tag Coagulation

Tag Embolism

Tag Hemorrhage

Year 2021

Keywords

Thromboembolic Disease

Accurate Diagnosis

Better Treatments

Sophia Chu Rogers

Laboratory Assays

Thromboelastography

Anticoagulants

Pharmacological Treatment Plans

Critically Ill Patients

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