Hello, my name is Stanislav Henkin, and I'm the Director of the Vascular Medicine Program at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire. And today, I'm going to be discussing the venous thromboembolism treatment guidelines with you. I have no disclosures pertinent to this presentation. So our learning objective today is quite simple. It is to select the best anticoagulant for initial management of acute venous thromboembolism, including the drug, the dose, and the duration. And to achieve this objective, we will take a look at two guidelines today. This is the antithrombotic therapy for VTE from the CHESS guideline and expert panel report, as well as the American Society of Hematology 2020 guidelines for the management of venous thromboembolism, treatment of deep vein thrombosis, and pulmonary embolism. And I will provide you with both guidelines, as well as compare and contrast the guideline recommendations for specific patient scenarios. When we talk about different guidelines, we will talk about the strength of recommendation both from the guidelines as well as the certainty. And I will color code this for you. When the evidence is strong with high certainty, this will be in green. When the evidence is weak or conditional with moderate certainty, this will be in yellow. And when there is no evidence or it is thought to be harmful with low certainty, the harm will be in red and the certainty will be in orange. Now when we talk about venous thromboembolism, we have to break it down into several different time points. We have to break it down into initial treatment, the primary treatment, and the secondary prevention. First, when VTE or venous thromboembolism is diagnosed, the initial treatment is counted as the first 21 days, and this is when usually there is a lead-in with a certain anticoagulant to get to steady state. After that, it switches to primary treatment, which is considered three to six months. After that, this is when a lot of follow-up is necessary to understand why did this VTE develop and what do we need to do about the anticoagulation. And this is a time where we meet and discuss with the patient, do we stop anticoagulation? Do we continue anticoagulation? If with your patient you decide to continue anticoagulation, this turns from primary treatment now to secondary prevention, which may be considered long term. But it's important to remember that if you keep your patient on anticoagulation long term, they need regular follow-up at regular intervals, at least once a year, because benefits and risks of anticoagulation may change over time, and regular understanding of benefits of continuing anticoagulation versus stopping are necessary to know should you continue anticoagulation or stop anticoagulation. So let's start with case number one. This is a 24-year-old woman who presented with two days of pleuritic chest pain one week after right ACL repair. Her vital signs are listed here and include a heart rate of 85, a blood pressure of 125 over 75, and normal saturation on room air. Her physical exam is significant for right leg in a knee immobilizer and no left lower extremity swelling. Her medications are consistent with estrogen, progesterone, oral contraception, and that's the only medication that she's taking. And imaging is consequently obtained and shows bilateral segmental pulmonary embolism without right ventricular strain. Additionally, DVT duplex is obtained and shows left cap deep venous thrombosis. Labs are consistent with a hemoglobin that's normal of 14.5, platelets of 300, and normal creatinine of 0.75. So in a patient like this that we may see in the emergency department, we may need to consider does she need to be admitted to the hospital, and what anticoagulants should be used for treatment of this venous thromboembolism, pulmonary embolism, and caffeine thrombosis. So let's start off just a quick discussion of the spectrum of acute pulmonary embolism. Now this is different based on different guidelines, but we will talk about the ACCHA guidelines that we have. On one end, and the most common, is the low-risk pulmonary embolism. In low-risk pulmonary embolism, the patient is normal tensive and there are no markers of RV dysfunction, meaning that the troponin, proBNP, are normal, and the RV to LV ratio is normal on the CT and echocardiogram. On the other end of the spectrum, unfortunately, the least common is the massive pulmonary embolism, and this is a clinical diagnosis in which there is hemodynamic instability due to pulmonary embolism, and in these cases, advanced therapies are required to improve patient outcomes. In the middle is the submassive pulmonary embolism, which comprises about 25% of patient presentations of pulmonary embolism. Now these patients are normal tensive, but they have markers of RV dysfunction, whether that's increased RV to LV ratio and or elevated troponin and proBNP, and different treatments may be necessary for initial treatment of these patients, and as we go through the guidelines, it's important to remember the different spectrum of the acute pulmonary embolism. Now, I can say that our patient that we met in the emergency department has low-risk pulmonary embolism. She's hemodynamically stable. She has no markers of RV dysfunction, and her vital signs are stable, and in patients with low-risk pulmonary embolism, outpatient treatment over hospitalization can be adequate. Now it's important to remember that outpatient treatment over hospitalization is reasonable if you have access to medications, ability to access outpatient care, and home circumstances are adequate. It's important to remember all these points when discharging your patients from the emergency department or even seeing them in the office. They need to have good follow-up. They need to afford their medication. You need to have follow-up plans for them, and both guidelines provide that this is reasonable. The CHESS guidelines actually recommends this as a strong recommendation with low certainty as opposed to American Society of Hematology provides this as a weak or conditional recommendation with low certainty. Now next we need to talk about choice of anticoagulant in this case, and both guidelines suggest that apixaban, dabigatran, edoxaban, or roviroxaban are more reasonable over vitamin K antagonists in most situations, and the CHESS guidelines recommend this as a strong recommendation with moderate certainty as opposed to American Society of Hematology describes this as a weak or conditional guideline with moderate certainty. And importantly, both guidelines say that no specific direct oral anticoagulant is recommended. They are all reasonable and should be first choice over vitamin K antagonists in most scenarios. Now it's important, and you will hear in my presentation as well as different presentations about where vitamin K antagonists may be more appropriate, but in most scenarios, direct oral anticoagulants are recommended over vitamin K antagonists. And American Society of Hematology recommends this as a weak or conditional recommendation with low level of certainty. And your choice of anticoagulant should really depend on affordability and availability of different anticoagulants in different pharmacies as well as your own hospital. Now it's important to remember the dose in anticoagulants for acute venous thromboembolism. When you talk about roviroxaban and apixaban, there is a lead-in period with higher dose of these anticoagulants, with roviroxaban is dosed at 15 milligrams twice daily for 21 days, and then 20 milligrams daily thereafter, and it's important to remember that roviroxaban should be taken with food. On the other hand, apixaban is dosed as 10 milligrams twice daily for seven days, and five milligrams thereafter, apixaban does not need to be taken with food. On the other hand, dabigatran and adoxaban, as well as warfarin, need to have a lead-in period with enoxaparin or unfractionated heparin. Both dabigatran and adoxaban should have at least five-day overlap with either enoxaparin or unfractionated heparin. For outpatient treatment, certainly enoxaparin is the choice of a heparin, but you need to remember that renal function needs to be normal or at least checked regularly in order to use enoxaparin, or dose reduced if renal function is abnormal. Unfractionated heparin or enoxaparin needs to be continued at least until INR is two if warfarin is used, and then can be stopped and warfarin continued. All right, let's go with the next case. So this is a 65-year-old woman who presented with three days of abdominal pain. These are her vital signs, her heart rate is 110, blood pressure 155 over 85, and she has normal saturation and room air. On physical exam, her abdomen is diffusely tender to deep palpation without carding. Her medications include umlodipine and atorvastatin, and her imaging shows colitis without obstruction or abscess. There's also left lower segmental pulmonary embolism that is incidentally noted. Her labs are significant for elevated white count of 16,000, normal hemoglobin, normal platelets, and creatinine of 1.2. So in asymptomatic PE, which is what we're talking about here, in patients with incidentally discovered asymptomatic pulmonary embolism, suggest same initial and long-term angiocoagulation as for patients with symptomatic PE. So that's important to remember. If you incidentally discover PE, they need to be treated the same way as if they were discovered for symptomatic patients. And the CHESS guidelines recommend this as a weak conditional recommendation with moderate certainty. Let's go on to case three. A 45-year-old man presents with right ankle pain and swelling after a basketball game. His vital signs are listed here and include a heart rate of 70, blood pressure of 120 over 75, respiratory rate of 80, and normal saturation room air. His physical exam shows trace right ankle swelling with no ecchymosis and full range of motion with minor ankle pain. He is on no medications. Imaging is obtained, including an x-ray, which shows no fracture. Due to swelling, a DVT duplex is obtained and shows non-occlusive acute soleal vein DVT. His labs are shown here and include hemoglobin of 13.5, platelets of 280, and creatinine of 0.9. So question to consider here is, does this patient need angiocoagulation with isolated deep vein thrombosis? So for isolated distal DVT, if there is no severe symptoms or risk factors for extension, serial imaging once a week for two weeks is suggested over anticoagulation. And the CHESS guidelines suggest this as a weak or conditional recommendation with low certainty. However, you need to consider risk factors that may increase the risk of propagation. And risk factors to consider include multiple veins that are involved, close to proximal veins, so such as popliteal vein, active cancer or receiving treatment for cancer, history of venous thromboembolism, either pulmonary embolism or deep venous thrombosis, inpatient status, highly symptomatic patient, a lot of swelling, a lot of pain, COVID-19 status, so COVID-19 positive, even as an outpatient, or preference or ability to undergo repeat imaging. So it's important to recognize that if you and your patient decide to undergo serial imaging, patient follow-up and ability to undergo serial imaging is an important factor to consider, whether to anticoagulate or not to anticoagulate and to perform serial imaging. So in this case, patient elects to undergo serial imaging rather than anticoagulation. He presents a week later with worsening red low extremity swelling up to the knee. His low extremity pulses are normal. A follow-up DVT duplex is obtained and shows extension of acute DVT into the popliteal and femoral veins. So if you have extension of calf DVT now into proximal vein, anticoagulation is recommended if thrombus extends into the proximal veins. And this is a strong recommendation with moderate certainty from the CHESS guidelines. The American Society of Hematology does not provide guidelines for this specifically. And home treatment over hospital treatment is suggested if you feel that the patient does not need hospitalization for other reasons or there is no significant symptoms that will require hospitalization for DVT specifically. American Society of Hematology describes this as a weak or conditional recommendation with low level of certainty. So now let's talk about acute proximal DVT. So this is when deep vein thrombosis involves the popliteal vein or femoral vein and or extension into even more proximal iliac vein as well. And in most patients with acute proximal DVT, anticoagulation alone versus interventional therapy is recommended. And when we talk about interventional therapy, we may talk about thrombolytics, mechanical or pharmacomechanical. And the CHESS guidelines, the American Society of Hematology both recommend this guideline as a weak or conditional recommendation and CHESS guidelines recommend this with a moderate certainty as opposed to American Society of Hematology recommends this with low certainty of evidence. You may need to consider interventional therapies if there is a limb-threatening DVT, so phlegmasia. Symptomatic iliofemoral DVT in younger patients with low bleeding risk. And the guidelines do discuss catheter-based intervention versus systemic thrombolysis to decrease the risk of bleeding in these patients. Now let's talk about acute proximal DVT and whether IVC filter may be necessary in these patients. So when we talk about IVC filter in addition to anticoagulation, the CHESS guidelines say that there is no reason to put an IVC filter if the patient can be anticoagulated. And they actually put this as a harm evidence with moderate certainty. Now if there is contraindication to anticoagulation such as active bleeding, recent stroke including ischemic or hemorrhagic stroke, inability to anticoagulate because of impending surgery, CHESS guidelines then do recommend an IVC filter with moderate certainty. And it's important to remember that IVC filter then should be retrieved if possible after contraindication to anticoagulation has resolved. Now if there is significant pre-existing cardiopulmonary disease, and the guidelines really don't talk much about what this specifically means, so there is a lot of room for interpretation, but this may be somebody with significant pre-existing pulmonary hypertension, significant COPD, heart failure with reduced ejection fraction, IVC filter may be considered, and this is a weak or conditional recommendation with low certainty from the American Society of Hematology. But it's important to remember that if you do put in a filter to take out the IVC filter as soon as possible, and processes need to be in place to remember to do these as really a minority of IVC filters are routinely taken out when they should be taken out. Let's talk about acute deep venous thrombosis and compression therapy. The guidelines suggest that compression therapy does not need to be routinely used to prevent post-thrombotic syndrome. And both the CHESS and American Society of Hematology give this recommendation a weak or conditional recommendation with low level of certainty. Let's go to our next case. A 55-year-old man presents with syncope one month after left total hyperarthroplasty. He's tachycardic, he's hypotensive, and his saturation is 82% in room air. His physical exam is significant in that he appears acutely ill and short of breath, and he's tachycardic without murmurs. His only medication is aspirin 325 milligrams daily. He undergoes Imogen, which shows CTAPE protocol with extensive bilateral pulmonary embolism with RV strain. His labs are significant for normal hemoglobin and platelets, creatinine of 1.1, and elevated troponin to 0.25, and pro-BMP to 3,400. So in this case, this is a massive pulmonary embolism, and I remind you that this is a clinical diagnosis. Now, hemodynamic instability can be defined either as cardiac arrest due to pulmonary embolism, obstructive shock with systolic blood pressure of less than 90 millimeters of mercury, or vasopressor support to achieve blood pressure more than 90, and end organ perfusion, or persistent hypotension, or drop more than 40 millimeters of mercury without other cause. It's important to remember that no matter what definition you meet of massive pulmonary embolism, the fact is that the hemodynamic instability needs to be due to pulmonary embolism and not another reason. So if you have a massive pulmonary embolism like this patient, systemic thrombolysis over no thrombolysis is recommended if there is low bleeding risk. The CHESS guidelines give this a weak or conditional recommendation with low certainty, as opposed to American study hematology give this a strong recommendation with low level of certainty. And in both cases, systemic thrombolysis over peripheral vein thrombolysis, so meaning catheter or direct thrombolysis, is recommended for massive pulmonary embolism. And both the CHESS and the ASH guidelines give this a weak or conditional recommendation with low level of certainty. If, however, there is high bleeding risk or failed systemic thrombolysis, such as there is ongoing hypotension due to pulmonary embolism, or there is shock that is likely to cause death before systemic thrombolysis can take effect, because usually this is a two-hour infusion protocol, consider catheter or direct-assisted therapies to assist in treatment of patients with massive pulmonary embolism, in addition to systemic thrombolysis in most cases. And the CHESS guidelines do give this a weak or conditional recommendation with low certainty. So now let's talk about duration of anticoagulation. So we talked about the primary phase, which is a three-month treatment phase, and the CHESS guidelines do give this a strong recommendation with moderate certainty. And there can be a three- to six-month treatment phase, over six- to 12-month primary treatment phase, and American study hematology gives this a weak or conditional recommendation with moderate level of certainty. So shorter primary treatment over longer primary treatment. Now when we talk about secondary prevention or extended phase anticoagulation, a finite, which is three to six months of anticoagulation, is recommended if VTE was provoked in the setting of major transient risk factor, and the CHESS guidelines do give this a strong recommendation with moderate certainty. American study hematology gives this a weak or conditional recommendation with moderate certainty. Now when we talk about major transient risk factor, we're talking about surgery with general anesthesia, hospitalization with inpatient status for more than three days, major trauma, or cesarean section. Now finite course of anticoagulation is also recommended in the setting of minor or transient risk factor, and both the CHESS and the ASH guidelines give this a weak or conditional recommendation with moderate certainty. When we talk about minor transient risk factor, we're talking about surgery with anesthesia less than 30 minutes, inpatient hospitalization for less than three days, acute illness at home for more than three days with really bent-bound status, estrogen therapy, pregnancy and peripartum, or leg injury with decreased mobility for more than three days. When we're talking about type of anticoagulation, low dose epixaban or rivaroxaban over standard dose epixaban or rivaroxaban is given a weak or conditional recommendation with low certainty from the CHESS guidelines. On the other hand, either low dose or standard dose epixaban or rivaroxaban are recommended by the American study hematology as a weak or conditional recommendation with moderate certainty. When we're talking about low dose epixaban, we're talking about two and a half milligrams twice daily or rivaroxaban 10 milligrams once daily with food. It's important to remember that anticoagulation is recommended over aspirin or no therapy if you do decide to go with extended phase anticoagulation and both CHESS as well as American study hematology give this a weak or conditional recommendation with moderate certainty. Now again, to put everything in perspective, we can put everything together in terms of initial management, the primary treatment and secondary prevention. And this shows you the correct dosing of different anticoagulants, including direct oral anticoagulants, low molecular weight heparin or warfarin for dosing. To remind you that rivaroxaban and epixaban need different dosing for the first 21 days for rivaroxaban and seven days for epixaban. Dabigatran, doxaban and warfarin need a lead-in period with enoxaparin or unfractionated heparin. For secondary prevention, rivaroxaban or epixaban can be decreased to 10 milligrams or two and a half milligrams respectively if that is what you decide to do, as opposed to dabigatran stays at the same dosing for 150 milligrams twice daily and warfarin stays at the same INR goal of two to three. I thank you for your attention.

venous thromboembolism

treatment guidelines

anticoagulant options

pulmonary embolism

direct oral anticoagulants

distal deep vein thrombosis