Okay, I'm going to be making sure I do this before lunch, right? Get you over to lunch. So this will be the last talk for the morning, and it's going to be on venous thromboembolism. This talk will largely focus on venous thrombosis and pulmonary embolism. I think for the boards, most of the questions are probably going to be on the management side of things, so I think that will be mostly the focus. I threw in three practice questions just to keep it interesting, but I'm really going to focus a little bit more on diagnostic and prognostic criteria. Management will be the bulk, and then a slide or two on prophylaxis. We all know how common DVT and pulmonary embolism are. There are many risk factors, some modifiable, some not. In the ICU, we have patients that are immobilized on mechanical ventilation with catheters, sedated, maybe immobilized for some time. These are just risk factors that we have to contend with. For some of the questions, they might start you off with somebody that might have a hereditary deficiency, such as factor V Leiden or Petromian gene mutation. Remember some of these hereditary risk factors. Of course, patients with comorbidities are going to be more likely to get venous thromboembolism as well. Ninety percent of clots in the lung originate from the legs, and so oftentimes the DVT is unilateral. You get unilateral swelling. You get tenderness, erythema. You all know the Hoffman sign. Duplex Doppler of the lower extremities are the most common way in which we diagnose DVT, and the treatment of a PE from a DVT is most likely going to be the same, unless, of course, you need an IVC filter because anticoagulation is contraindicated. The pathophysiologic response to pulmonary embolism is threefold. You have pulmonary infarction. You have ischemia. You have hypoxemia due to ventilation-perfusion mismatch and interpulmonary shunting. Hypercapnia and acidosis is very rare unless the patient is in shock. Hypotension, of course, is what you'll see in patients with massive PE, and the most common cause of death in severe PE is still right ventricular failure. PE is classified now into low-intermediate risk, or what we used to call submassive PE, and high-risk, what we used to call massive PE. Of course, high-risk PE is commonly associated with a higher mortality of over 15%, and these are patients who have PE who have hypotension shock or persistent arterial hypotension. From the PIUPED study, the Prospective Investigation of Pulmonary Embolism Diagnosis II back in 2007, the three most common features for a patient with pulmonary embolism are dyspnea, tachypnea, and pleuritic chest pain. Cough or hemoptysis actually is not very common, less than 50%, and so is swelling of the leg. Syncope, you have to know because that's a very important feature. Many patients who have massive pulmonary embolism and present with syncope have a very high likelihood of not doing well and even expiring, so it's a very critical sign to look for in patients that you're suspecting to have had PE who present with a syncopal episode. Chest radiographs are commonly normal in up to a quarter of patients, and when you do find something on a chest film, it's usually either unilateral atelectasis, pleural effusion, elevated right diaphragm, but two uncommon characteristic findings for PE are one of them is the Hampton sign or hump, which is basically a rare sign of pulmonary infarction characterized by this wedge-shaped infiltrate or opacity seen laterally on a chest film, and the Westermark sign is the other infrequent sign where you have a cutoff of the pulmonary vasculature, so you see an area of oligemia or reduced blood flow on a chest X-ray. Blood gases, up to 40% of patients with pulmonary embolism will actually have a normal O2 sat. Hypocapnia is very common. Patients are tachypneic. They have respiratory alkalosis. ECG can sometimes be helpful. Tachycardia is the most common electrocardiographic abnormality. You can get nonspecific SCT wave changes. That can happen. Atrial dysrhythmias, new arrhythmias in particular, and even new right bundle branch block as shown on the ECG on the right is also something that might make you suspect in the right context that the patient may have a pulmonary embolism. D-dimer. D-dimer is a good rule-out test. I don't do it very commonly because I treat many patients with cancer, and so it's not a good test for that. It's frequently elevated in patients not only with cancer, advanced age trauma, and recent surgery. So it has very poor specificities. It's a good rule-out. If your suspicion is low and the D-dimer is flat or negative, then that helps you maybe avoid further diagnostic testing. But in most hospitalized patients, particularly those that admitted to the ICU, it's not a test that's extremely helpful. In patients that cannot get a CT scan, it's probably highly unusual, but if this happened that you don't have a CT scan available in your institution, I doubt that happens anymore. But in patients with renal failure, contrast eye allergy, a VQ lung scan, even just a perfusion scan would be enough. And it has a very high negative predictive value of about 97%. So a normal VQ scan essentially rules out a PE pretty much with high confidence. And so is a high-probability scan gives you up to 90% indication that the patient has pulmonary embolus. The only problem is that if you get a VQ scan in most patients, it comes back with this non-diagnostic probability in about 30% to 50%. So you still have to work up the patient if the VQ scan comes back intermediate or non-diagnostic. We do a lot of point-of-care ultrasound and formal echocardiograms, and the key feature that you want to look for, as you can see on this echo image, is a very dilated right ventricle. So right ventricle actually, as it becomes dilated, starts pushing on the septum, and so the LV gets a little squeezed. And so you have a very prominent right ventricular size on the echocardiogram. In patients that develop severe right ventricular dysfunction, you can also see evidence of tricuspid regurgitation, paradoxical motion of the septum, and there's a decrease in the LV-RV ratio as well. In terms of prognosis, the PESI score, or what we call the pulmonary embolism severity index, is, I think, very popular. It's most commonly used in algorithms. You get a point for each of these six criteria that's listed here. We always get a point because our patients have cancer, but elderly patients, those with history of heart failure, chronic lung disease or tachycardic, systolic blood pressure less than 100, O2 sat less than 90, you get at least one point for each of those, and usually those are indicators. Just giving just one point already puts the patient at a higher risk category than other patients who may not have any of these other variables. So first practice question for you. Which of the following findings is associated with the diagnosis of acute pulmonary embolism? A, pleuritic chest pain and hemoptysis are present in the vast majority of patients. I told you, I indicated to you that's not very common. It's only present in less than 50% of patients. B, a normal right ventricle on echocardiogram rules out clinically significant PE? Not necessarily. There are situations where the right ventricle is not maybe normal. An elevated D-dimer is diagnostic? No, in a cancer patient, it's usually elevated. So correct answer here is a biomarker, such as BNP and troponin are frequently elevated, and when they are elevated, they're usually indicative of a more serious course for the patient that has pulmonary embolism. So correct answer here is D. So let's talk about biomarkers. We get a lot of biomarkers for patients that we're suspecting acute coronary syndrome, maybe heart failure, we're checking a BNP troponin. But in patients with PE, it's good to get these biomarkers as well, because if they're elevated in the presence of other features related to pulmonary embolism, that usually indicates that over the course of that patient in the ICU or in a step-down unit, they're likely going to have some sort of adverse cardiovascular outcome, whether it's some dysrhythmia, right heart failure. It's just a high indicator of something bad that's going to happen to the patient. So let's talk about management. Anticoagulation, of course, is key in patients with pulmonary embolism. You can't wait for the results of diagnostic testing. Unless there's a very strong contraindication not to give an anticoagulant, you should treat the patient while waiting for the outcome of diagnostic testing. For patients where you objectively already confirmed they have a PE, for example, on a CTA, then you need to start treatment with either a direct anticoagulant, low molecular weight heparin, or fundoparanox. That's if they are hemodynamically stable. So you would favor those agents over unfractionated heparin. However, in the hemodynamically unstable patient with pulmonary embolism, you have to favor unfractionated heparin, especially in those with severe renal failure, with creatinine clearances less than 30, morbid obesity, or extensive clot burden. You want something that you can start and stop. You can titrate to an anti-10A or maybe an APTT, if that's what you're still doing. But you want something that's short that you can reverse with protamine. So these are all advantages, particularly in our very sick, critically ill patients in the ICU. What about subsegmental CT in an era where we're getting a lot of CAT scans? You know, you pick up something, you are not suspecting PE, and then there's a report, hey, this patient has subsegmental PE. So the recommendation from the most recent CHESS guidelines from 2021 suggests that first get a lower extremity ultrasound and see if there is any clot or not. If there is a clot, okay, then you treat the patient like you would others, vice versa, just because they have subsegmental PE. However, if they don't have a proximal leg DVT and they're at low risk for recurrence, you don't necessarily have to treat that patient with subsegmental PE. Clinical surveillance is still favored in those patients. When you do use anticoagulation therapy, as I mentioned, unfractionated heparin is usually titrated to an anti-10A. Does anybody not do anti-10A here in the group? You all do anti-10As now? Nobody follows APTT anymore? Great, because a few years ago when I gave this talk, they were still doing APTTs. But anyway, anti-10A, you want to be somewhere in that 0.3 to 0.7 range for your appropriate levels. Of course, you can substitute low molecular weight heparin. Warfarin and oxaparin is more commonly used when the paranox is a 10A inhibitor. That can also be used. And then you have patients, for example, who may have HIT, as we heard from our previous speaker, where you might need to use argatroban. And then you have your DOACs, such as rivaroxaban and epixaban are very popular. There's one situation where, again, a vitamin K antagonist like warfarin might be favored, and this might be a test question because they're going to give you choices such as DOAC or maybe a low molecular weight heparin or warfarin. And although we're going away and away from using warfarin in many patients, you have to be careful that DOACs would not be great for patients with advanced kidney or liver failure. And particularly for patients with triple positive APS or antiphospholipid syndrome, that might be a test question, who have an arterial thrombus, vitamin K antagonists are favored over DOACs in those situations. Vitamin K antagonists like warfarin and DOACs are contraindicated, of course, in pregnancy. Complications. I think we heard briefly that heparin can be associated with bleeding and or HIT, which is an autoimmune situation caused by platelet factor 4 and acting on the platelets, and you get this paradoxical arterial thrombosis as a result. Bleeding, of course, is an important issue. Fortunately, you have protamine that can reverse. So for every 100 units of therapeutic heparin that's been administered to the patient, you can give a milligram of protamine. So this is usually a slow IV infusion over 20, 30 minutes of at least 50, sometimes 60 milligrams of protamine, depending on how much heparin you've used. Low molecular weight. The advantage of low molecular weight heparin is that they have greater antitannate, which is clearly much more efficacious in the anti-clotting cascade. Inoxaparin, you can see the dose there. Routine anti-factor 10A levels are not indicated if you're using low molecular weight heparin. In special situations, though, there can be a problem with obese patients, renal failure. We have to be careful about dosing. And in those patients, I usually, if I'm going to stay on low molecular weight heparin, I like to check my anti-10A. And unlike unfractionated heparin, there's less ability to reverse heparin effect with protamine, so especially if they have received the low molecular weight, let's say, injection more than eight hours, there's less likelihood of success in reversing that patient. But if they're within that six, eight-hour window of getting the low molecular weight heparin and they're bleeding and need to reverse it, you can still use protamine in that circumstance, but you probably won't be as successful as when you reverse heparin effect with protamine. Duration of anticoagulation is three months for most patients, and those with indications for extended duration of treatment are those patients with unprovoked pulmonary embolism or they have a persistent risk factor. That would be my kind of patients where they continue to receive chemotherapy. There's always a risk factor that's involved. They've had a clot. They've had a PE episode. Usually those patients are treated for longer duration. And when they do get substituted to a direct oral anticoagulant like apixaban or rivaroxaban, which are the two most common agents, we usually give them a reduced dose. So from treatment dose, they stay on a reduced dose. So let's say five milligrams, for example, or 2.5 of apixaban is very common. There are some assessment tools to predict patients more likely to develop recurrence. Males tend to have more likely to have recurrence. And those that have a high D-dimer at the end of the three months are usually patients that are also more likely to have an indication for a longer duration of anticoagulation therapy. IBC filters, again, there's less and less use of IBC filters now. The indication is only in patients who have an absolute contraindication. They can't get an anticoagulant, or you've given them an anticoagulant, and they have a complication like bleeding, HIT, something that precludes them from getting further treatment other than an IBC filter. Those would be the only circumstance. Those who have recurrent PE despite adequate anticoagulation, we tend to put retrievable now. So you can take it out in five months if the risk factor is gone. Most interventional radiologists can remove an IBC filter within a few months of insertion if it's a retrievable filter. Complications are thrombosis at the insertion site, and some patients can be left with very debilitating post-thrombotic leg syndrome, edema, swelling, difficulty of ambulation. Some of these filters, and I've seen a few of these, where they can actually fracture, they can migrate, and they have to be fished out. It's a messy scene for an interventional radiologist to deal with that. This is an important study that might come out on the boards. This was to see if you add an IBC filter to anticoagulation, is that better than anticoagulation alone? So this was over almost 400 patients. They found no difference with the IBC filter plus AC versus AC alone in terms of recurrence of symptomatic PE at three months. And so they concluded from this study that it should not be routinely performed to put IBC filters in, and they should only be reserved consistent with the guidelines in those patients that have a contraindication to receiving anticoagulation therapy. Second practice question for you is a 65-year-old male, pancreatic cancer, comes into the ED short of breath. His blood pressure, pay attention, 82 over 45. His tachycardic to 110. His afebrile, his O2 sat is 87% on room air. You can see his physical exam there. His CBC chemistries are normal. Chest X-ray, mild increase in pulmonary vascular markings. He has T-wave inversions in lead III and anterior precordial leads. Echocardiogram shows RV dilatation, leftward shift of the septum. His LV ejection fraction is 45%. BNP is elevated to 800. Troponin is elevated, 1.5. He's placed on high-flow nasal cannula to keep his SAT over 92%. And therapeutic heparin is started. Which of the following would be the next best step in managing these patients? Is it giving him dobutamine, 5 mcg per minute? You probably won't want to do that, right? He's already hypotensive. You're giving him a vasodilator that's going to further drop his blood pressure, even though he has maybe some evidence that he has right ventricular dysfunction. Giving metoprolol in somebody that's hypotensive just to treat the tachycardia probably won't be a good option. What about giving him a 2-liter fluid bolus? Why don't we just give him a fluid bolus of 2 liters just to get his blood pressure up? This patient, you probably won't want to do that, right? Because he has RV dysfunction. His right-sided pressures are high. You give him a 2-liter bolus, he's going to crash. He's going to develop further right ventricular failure. So this patient is hemodynamically unstable. He's got pulmonary embolism. You don't see anything in the story that there's a contraindication to giving him a lytic agent. So the correct answer here is giving him TPA, 100 mg IV over 2 hours. There are other options besides just TPA, and you can use tenecteplase. In a patient that's a higher risk for bleeding and you want to be a little bit more cautious, then you can give half-dose TPA. So you don't need to give 100 over 2 hours. You can give 50 mg and be just as fine. The only challenge with giving the half-dose is in some patients you need to further escalate the treatment. They end up getting the other 50, or you just have to give them additional other interventions. But there's no question that TPA administration, lytic administration usually reduces radiographic findings. Hemodynamic improvement is better. So it gets a grade 2B recommendation from the guidelines to use lytic therapy in patients with acute pulmonary embolism who are hypotensive, and hypotension here is defined as systolic blood pressure less than 90, who are at low risk of bleeding. This is another important study, the PITO study, which probably will be a very testable item on the boards, and you need to know this. In practice, this was a study looking at giving tenecteplase versus no tenecteplase in patients who had pulmonary embolism in the intermediate or submassive category. So they had evidence of right ventricular dysfunction, either on echocardiography or they had an elevated biomarker like a BNP or troponin, but not hypotensive. So systolic blood pressure was over 90. It was about 100 or more. And they looked at if I give a lytic in this patient on top of anticoagulation in a patient with submassive PE, will their outcomes be better than those treated just with anticoagulation alone? What they found is that the patients that were randomized to the tenecteplase group, they did have less likelihood of hemodynamic decompensation, but the flip side of that, they were at higher risk for stroke and intracranial bleed. So this is a risk-benefit discussion. If you're going to contemplate a patient that you think has significant risk factors with intermediate or submassive PE, you need to have a discussion in those patients about giving tenecteplase if you're going with tenecteplase or TPA in those patients. So again, the tradeoff is higher risk of stroke and intracranial bleeding, but better in terms of hemodynamic recovery. Next practice question, 55-year-old female, diabetic, hypertensive, is admitted to the ICU with swelling of the left leg, prior history of an MVA, requiring a right leg BKA, and a venous thrombosis of the right leg that required placement of an IBC filter. Blood pressure is 102 over 60. She's tachypneic, a bit on the low temp side. The left leg is very swollen, bluish discoloration around the ankle, foot, thistle, thigh. Pulses are palpable but decreased. White count is elevated at 25,000. Hemoglobin is 16. Protrombin time is elevated. PTT is over 100. D-dimer positive. You can see the electrolytes there. Bicarb is 14. Creatinine is 4.2. Which of the following is the next best step in the management of this patient? What do you think the patient has? Besides having some big clot down there. Anyone? What's your answer here? Do a left leg BKA above the knee. So she's already had a right BKA. Why not just do the left? That's too drastic. You don't want to do that. What about broad-spectrum antibiotics? Maybe she's septic. White count is elevated. But there's nothing in the stem that tells you anything. Low temp, sure, but white count elevated. But there's really nothing else going for that with the physical finding on the patient. IV heparin? Why not? PTT is already over 100. So she's kind of auto-anticoagulated, if you will. But there's a real problem with this leg. Yeah. Very good. So this is a patient. The correct answer here would be catheter-directed thrombolysis. So this patient has a blue painful leg. Plagmathia serrolia dolens. You've probably seen this at least once. Very catastrophic. And this is something that really needs very careful attention. This is the very primary indication to do catheter-directed thrombolysis. So patients at higher risk of bleeding with systemic lysis, so they can get IV systemic lysis, then you need to consider catheter-directed thrombolysis. So this gets a grade 2C recommendation from the most recent guidelines. So anybody with a massive iliofemoral DVT or has the syndrome of painful blue leg with symptoms for 14 days with good functional status are good candidates. And so in patients who have acute PE, hypotensive, and are high bleeding risk with systemic lytic therapy, or they failed systemic thrombolysis, or in shock, and or you have the appropriate expertise at your center, then you should consider strongly catheter-directed thrombolysis. Ultrasound-assisted. You probably do this in many of your centers. This is a systematic review meta-analysis. 16 studies, albeit 12 of them were retrospective case series. Only one RCT to date as of 2018, 2019. The ecosystem was used to break up the clot. Lysis was achieved in 77% to 100%. And this particular analysis demonstrated it appears to be safe. Bleeding events were reported in about 4% considered major. But I think the current data is still somewhat inadequate to make this a primary choice for treating DVT. But it's certainly getting more and more popularity, I think, in good candidates for ultrasound-assisted catheter-directed lysis. So I think this should be one of your primary options. You need to know the contraindications to lytic therapy, right? Known structural disease in the brain, previous surgery, ischemic stroke last three months, actively bleeding patients, patients with bleeding diathesis. Everything else outside of those major contraindications are what we consider relative. Very high blood pressure, if you can control it, should not be an issue. Non-intercranial bleed, you got away the risk-benefit. Recent surgery, depending how far, what kind of surgery. Recent invasive procedure, what kind of procedure. So these are all kind of relative contraindications. In a good candidate patient where you can offset some of these relative contraindications, there may be still a role for giving lytic therapy, particularly if they're in shock or hypotensive. What about percutaneous techniques? We have a lot of fancy catheters that our IR colleagues have that are able to break up the clot with pigtail or balloon catheters, hydrodynamic catheter devices, aspiration catheters. You've all seen them, and these are strategies that our interventional radiologists can now do in selected patients. Surgical embolectomy or thrombectomy still has an indication. If you have the appropriate expertise and resources to do it, certainly patients with massive BE, shock despite heparin and resuscitation, or they've been on lytic therapy and they're failing, they're still crashing. I think there's a reason to justify using surgical thromboembolectomy in these patients. More recently, some studies have shown that combining ECMO, bridging the patient's ECMO until they can get surgical embolectomy, particularly those with high risk who have already been either in cardiac arrest or in needing of CPR, there may be a role for combining ECMO in preparation to bridging the patient to surgical correction. Lastly, on prophylaxis for ICU patients that are high risk for bleeding, mechanical prophylaxis, of course, is recommended, but when the bleeding risk subsides, you should switch over to pharmacologic prophylaxis because mechanical prophylaxis is still superior than mechanical prophylaxis, and here you can use either low molecular weight or fundoparanox rather than unfractionated heparin. They just tend to be superior to unfractionated heparin. One study you need to know about is the PREVENT trial published in 2019 in the New England Journal. This was to try to see if you add mechanical thromboprophylaxis, SED, compression devices, to anticoagulation prophylaxis, is that any better than just anticoagulant prophylaxis? And the answer here was the addition of pneumatic compression devices for up to 18 hours a day, in addition to pharmacologic thromboprophylaxis, did not really reduce the incidence of DVT or death from any cause. However, caveat is that the incidence of VTE was lower than expected, and so it reduced the power of the trial. So in most instances, you always go with pharmacologic thromboprophylaxis, and in those patients that can be successfully treated with no contraindication to pharmacologic thromboprophylaxis, there is no additional advantage in putting mechanical prophylaxis on those patients. Of course, in fresh surgical patients where you can't use pharmacologic thromboprophylaxis until the surgeon tells you, okay, sure, you can start heparin or low molecular weight heparin, then you have to use mechanical prophylaxis in those patients. So key points, take home, high suspicion for PE, looking at diagnostic, echocardiography, biomarkers, anticoagulation appropriate in most patients over 90%, lytic therapy may be indicated in a subgroup of hypotensive PE patients, IBC filter only if there's a contraindication to anticoagulation, catheter-based techniques are getting more and more popular and becoming the go-to now in many patients, even those with intermediate risk PE. And don't forget about prophylaxis, always pharmacologic first and mechanical in those that cannot get pharmacologic thromboprophylaxis. Thank you very much for your attention. Thank you.

venous thromboembolism

deep vein thrombosis

pulmonary embolism

anticoagulation

prophylaxis

risk factors