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Lecture Hall Vascular Therapy | General

Venous Thromboembolism


Allan Hamdan
Allan Hamdan, MD
Director of Clinical Research
Division of Vascular Surgery
Beth Israel Deaconess Medical Center
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Lecture Transcription




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Good day, my name is Allen D. Hamdan. I am assistant professor of surgery, Harvard Medical School and director of clinical research at Beth Israel Deaconess Medical Center in the Division of Vascular Surgery. We are speaking today about the topic of Venous Thromboembolism.



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Deep venous thrombosis can start essentially anywhere in the venous system. It is most commonly seen in the lower extremities but it also to be identified in the pelvic veins or upper extremity veins. It is probably the most common preventable cause of hospital death. There are at least 250,000 new cases per year.



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Virchow’s Triad is a way to describe the common situations we may encounter that would lead to venous thromboembolism. One of the first necessary requirement is stasis. This essentially refers to pooling of the blood in areas such as a large varicose vein. Generally some injury to the vein wall is required. This can be an injury done by manipulation of the vein wall such as in a central line or an intravenous catheter. In that situation endothelial cell line would be denuded and the normal function of endothelium to prevent clotting of the blood on the ______ the vein wall would be damaged and finally some blood abnormality. This could indicate a hypercoagulation state, a change in the clotting cascade, or some exogenous administration of medications or blood product. For venous thromboembolism to occur, however, all these do not need to be present but this is just to give you a background and starting point from where venous blood clots occur.



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DVTs originate obviously in the venous system. This can be due to problems with the valves in the system and in fact the valves are often locations where venous clots start. This, however, is not to say that the patient’s just with simple varicose veins are at exceptionally high risk for DVT. It is just to give you a representation of how this may occur. This just shows the way a normal valve opens and closes. After a DVT, this can lead to significant damage and the valve cusp and a stiff, sclerotic, nonfunctional valve leading to continual reflux of blood. This can result in some of the problems of the postphlebitic syndrome which will be described on another slide. One of the most common locations of blood clot is in the soleal veins in the calf. These are obviously in the soleus muscle. This is likely due to the fact that they do not have valves and pooling of blood and stasis often occurs in that location. Also, as I stated there can be new valve cusps seen in cases of low blood flow. Also, as described in the triad, endothelial cell injury can occur due to local hypoxia and accumulation of coagulation factors and trauma. It is interesting to note that a large majority of patients who develop DVT after something such as major head trauma or major motor vehicle trauma this will occur in both legs and not necessarily in the limb that is most effected. So, for instance, the patient who has a tibiofibular fracture on the left leg requires surgery, immobilization, and prolonged hospitalization. It is even more likely to develop a DVT in the opposite leg or both legs. This just points out that it is not necessarily a local traumatic injury to the vein wall that leads to the problem but a overall systemic problem.



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Patients who develop DVTs often present with unilateral leg swelling as can be seen in this photo. The majority will have pain, tenderness to palpation especially in the effected area such as the calf and the thigh muscles. However, a number of DVTs are silent and that is why the condition must have a very high index and suspicion if a patient is not doing well after surgery or when seen in the office and has some symptoms regards to the leg but they are not clear cut for DVT. This is a situation where the whole clinical scenario of the patient is put into perspective.



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There are a number of risk factors that have been identified for the development of DVT. Certainly, the patient with ongoing malignancy is at a high risk. Surgery is probably the most important and relevant risk for what we do for a living. Certain surgeries will carry a much higher risk than others for instance a patient who is undergoing gastric bypass for morbid obesity is probably among the highest risk of developing a DVT. The flip side would be someone who is undergoing a local excision for something as simple as a mole, something in the middle risk would be a 2 or 3 hour procedure under general anesthesia for treatment of anything including a foot procedure, cholecystectomy, something along those lines. Patients who are admitted to the hospital for trauma are at very high risk and some more information on that was detailed on the previous slide as patients get older, their risk for DVT increases. That is not to say that young patients cannot develop DVT. In fact, those are the patients who have the highest index suspicion and a number of fatal events have occurred in young people after trauma that is related to an undiagnosed DVT and pulmonary embolism. Any sort of immobilization also increases the risk, so when you have a patient who undergoes a foot procedure and you recommend a period of nonweightbearing, just take that into account that if the patient develops a leg swelling or pain or has any pulmonary symptoms you should have these issues high in your list. Finally, patients who have had a prior blood clot in either leg or a strong family history for DVT those are the patients who really need to keep a watch out for.



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There are several causes of DVT. The first we talk about is injury or what is called an iatrogenic cause. This is seen when a line or IV is placed in the venous system. It is not necessarily that the line is placed improperly but with the catheter sitting in the vein especially in the smaller vein for prolonged period of time, a thrombus can develop around the catheter and then adhere to the wall. Patients who have hypercoaguable state at baseline are at a higher risk for DVT. There is a situation called the second hit hypothesis and what that means is for instance a very common mutation is called factor V Leiden. In that case, the patient has a mutation and their factor V Leiden protein that makes it resistant to lysis by activated protein C which is one of the stop gaps in the clotting cascade. Now patients who have one of the genes for factor V Leiden do not usually have primary DVT where they just develop it out of the blue so to speak but if someone has a factor V Leiden either diagnosed or undiagnosed and undergoes one of the so called lesser surgical procedures that we detailed such as an appendectomy or short procedure they may develop a DVT whereas the patient without that preexisting problem would not. That is not to say that some hypercoaguable state do not actually presents with _______ or primary DVTs but it is not as simple as you have a hypocoagulable state and you will develop blood clots.



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In general anything that causes a shift in the balance of the competing pathways of natural fibrinolysis and clotting can lead either to excessive bleeding or to excessive clotting. Thus things that essentially inhibit clotting such as antithrombin III, thrombomodulin with its associated protein C and S factors shifts in the balance where the activities of these with more ease can effect the clotting cascade. As I have stated before, it is not just as simple as the vein is injured. There is generally something else that needs to occur.



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I would like to spend a little bit more time in some of the hypercoaguable states. As a background, this is a field that is growing and every 2-3 years another major so called hypercoaguable state is identified. Patients may present to you with the biochemical diagnosis or this may be _______ to you. Some of the triggers would be things as simple as multiple miscarriages in a female or prior blood clot without any specific cause such as the patient who was active, has no medical problems, no admissions to the hospital, and just develops a swollen leg and a blood clot is diagnosed, or a major family history of blood clots. Some of the states that are common would be deficiency in antithrombin III, protein C or S as described in prior slide, factor V Leiden as mentioned, and probably one of the more common conditions which is called the prothrombin gene mutation, that shows specifics of these condition is not as crucial as to identify that they exist and that a patient who you are seeing may have a mutation in one of the proteins and it has not been diagnosed as of yet. Pregnancy in itself probably carries some increased risk of clotting although it is somewhat arguable and then there is a big group of patients who have the idiopathic or unknown cause of hypercoagulable state. These are generally patients who have multiple clotting episodes without any biochemical marker.



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Some of the things that are important from a surgical standpoint are both as I mentioned the high index of suspicion and early diagnosis but also prevention. This is both prevention in patients who are hospitalized for nonsurgical treatments such as severe infections or cellulitis. Patients who are about to undergo a surgical procedure, those patients who are postoperative from the procedure. What is detailed in this picture is compression stockings. In a way themselves, they probably have a fairly low benefit of prevention although they can be used in patients who are now starting to ambulate and to mobilize and who are at lower risk. One of the most important things is to allow early mobility in any patient who you think it is reasonable certainly if it just performs a transmetatarsal amputation and you do not want the patient walking around but you have to take into your account you are going to increase the risk of DVT by keeping them on bedrest and nonweightbearing. Venodyne boot or the sequential compression devices are incredibly effective. However, as a number of people state they are only effective if they are on the patient. What that means is there is often a very low compliance with the nursing staff and with the patients and you might order Venodyne boot and find that it is sitting against the wall nicely pumping away but not on the leg. The other important thing is that if you are trying to use it for DVT prevention perioperatively, it really needs to be placed in functioning before general anesthesia is induced. Approximately 40-50% of DVTs occur during the induction or early part of surgery and that is when it is crucial to prevent. Another very effective and probably the most effective way to prevent DVT, and this is both in a perioperative sense as well as a postoperative sense is the use of subcutaneous heparin the standard dose is 5000 mg subcutaneous three times a day. If you are using it as a perioperative treatment you would like to have it injected subcutaneously one half hour before the surgery starts and there is a small increased risk of hematomas and wound bleeding but depending on the risk of the patient it is certainly a worthwhile treatment. Coumadin is often used in bony procedures and is very common in such things as the patients are undergoing a hip replacement or knee surgery. It is an effective regimen as long as it started early enough perioperatively to have the effect. Aspirin probably has very little benefit but a number of patients who have vascular disease and have undergone foot procedures or bypass procedures would be on aspirin. Stockings as mentioned are generally good thing in the early recovery period but in itself would certainly not be primary prevention method.



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Diagnosis of DVT other than the clinical suspicion as I try to hammer into your heads can be done in number of ways. This is the most common way to diagnose a DVT and this is using an ultrasound. This is a gray scale depiction of a vein without any thrombus in it or so called normal vein. As far as physical examination, there is a sign called the Homans sign, which is essentially pain in the calf muscles and the passive flexion and extension of the foot. It is incredibly unreliable and it is basically as good as flipping a coin. If that is not the say then you should examine the patient. Certainly, any unilateral findings as detailed in the prior studies, swelling, pain, and sometimes early redness in an area where you would not expect cellulitis. These are the things that would trigger you. Ultrasound is the most sensitive, cheap, quick, and ordered tests to identify DVTs. Another potential way of identifying whether a patient has DVT if your are unclear and this is generally used in patients who are not in the perioperative period is the ordering which is called D-Dimer. Basic elevated D-Dimer in the blood indicates that there is a clotting cascade that is underway and is a good negative test. What that means is in a patient who you are not sure who may be has an equivocal ultrasound test. If the D-Dimer is negative, it is very unlikely that the patient has a DVT. In the positive, it can be important but just to understand if you are to perform a transmetatarsal amputation and the patient was admitted with infection before that, the D-dimers that can be elevated and it is just a reflexion of the inflammatory process and in itself is a positive value that is not crucial.



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This is an ultrasound depiction of deep vein thrombophlebitis where echogenic thrombus is within the vein wall itself. This is first seen as the vein losing its compressibility. What that means is as the ultrasound technologist is passing a probe over different veins, when they look at one of the most important veins of the common femoral veins they can actually use their probe to press down on it. They should be able to put the two vein walls together completely occluding the vein for a short period of time. If there is clot within the vein when they try to press it they will not be able to put their walls together. That is one of the most important findings. The other obvious finding in this is often seen a little bit later after a vein loses its ability to compress is a diminished blood flow through the venous segment. Another important point worth mentioning is although it is anatomically incorrect people often refer to the deep vein that is between common femoral vein and the popliteal vein as the superficial femoral vein. It is better referred to as just the femoral vein. However, having said that if you have clot in the superficial femoral vein, this is still a DVT. The reason I mentioned this is they did a study years ago of primary care doctors and asked how many of the doctors in the survey would treat a patient with a clot in the superficial femoral vein and remarkably only 20% of the physicians recognize this as a true DVT. The other thing that is important is the ultrasound is just the snap shot just like any other test. If you have a high index of suspicion, repeat it at an interval several days to a week, if the patient is clinically well or if you are convinced and the patient has a negative DVT you can perform other studies.



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Some of the other studies that can be helpful are MRV which is a venous study using an MR machine or what is called a CTV which is basically a CT scan with contrast and it is time for the venous phase. These are particularly helpful in situations where you think the clot may be more proximal such as in the iliac or pelvic veins. Remember a lower extremity study will really just get you to the lower external iliac vein and the common femoral vein area and more distally. If you had a proximal DVT although there might be some signs in the lower extremity, it is not always as simple as that. So these are tests that can sort out a controversy so to speak. Patients can be identified by these tests mentioned above with intrinsic problem so vein wall disease damage or strictures due to prior catheterization and can also identify extrinsic compression such as a cancer, an ovarian tumor or something along those lines. One thing to remember and this is not to say that if ultrasound in negative you should stop there but when ultrasounds are ordered without any clinical signs whatsoever in the extremity, in other words no pain, no swelling, no redness and both legs are symmetric and without symptoms, an ultrasound in that situation is almost always negative.



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The treatment of a deep venous thrombus is multifactorial. The goal standard currently is, what is called, unfractionated heparin and that is the standard heparin medications. This is something that has to be done in the hospital. It is given intravenously with measurements of the prothrombin time and the PTT measured at intervals. A newer method, which is probably equally effective and may be more effective is the so called low-molecular-weight heparin. This is basically a more purified heparin, which has less binding to proteins in the blood and is more reliable. This can be done in subcutaneous injections as an outpatient in the appropriate patient. Coumadin is the eventual transition therapy after the patient has been appropriately heparinized and an important thing to remember is often bed rests is what caused of DVT or was a causative factor, as I should say. Patients who have DVTs unless they are massive and you need to keep them in bed with their legs up to get the swelling down do not necessarily have to be on bedrest that is essentially an Old Wife’s Tale and mobility is not going to shake the clot loose so as to cause a PE in majority of patients.



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One of the important things to remember is that the primary treatment of DVT using Coumadin and heparin is to prevent propagation of clot. These medications do not dissolve clot. Now having said that halting the process allows the switch in the balance of the two cascades as I have mentioned before and allows the body to switch more towards fibrinolysis to lyse the clot over time. But the reason to do this is to prevent the clot from extending more proximally and eventually becoming a pulmonary embolus that is your major first line of treatment. Now in very special circumstances things such as TPA or urokinase are used generally directly into the clot to perform rapid lysis. The reason you may use this is in someone who has got a massive pulmonary embolus and is dying from it or a patient who has a massive swollen leg from a DVT in the iliac vein and is in risk of losing the leg if the clot is not relieved.



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The treatment protocol for the intravenous unfractionated heparin is generally an initial bolus of 82-100 units per kg so for patient who is 70 kg may get somewhere between 5 and 7000 as a bolus and then the maintenance drip is 18 u/kg per hour as a drip. You want a PTT of somewhere in the 60-80 range but I would caution you that every lab has their own reagents and their own values and you should refer to the pharmacy manually or hospital on the computer to identify what are the appropriate ranges. Another way to treat DVTs is a 1 mg/kg of Lovenox administered subcutaneous twice a day. This is the medication called enoxaparin. It is a low-molecular-weight heparin or purified heparin and one of the nice things about it is since it does not have a lot of plasma protein binding is except in extremes of obesity or really small patients, you just give the dose based on the weight and there is really no tests that can be done or should be done. It really does not affect the PTT. The only test that can be useful in monitoring Lovenox in very unique situation is what is called the antifactor Xa activity. Generally, after you start the heparin in the patient who is appropriately therapeutic in the PTT range over the next several days you start Coumadin and aim for an INR of 2.5.



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As I stated before a low-molecular-weight heparin has been studied and can be used to treat a patient with DVT as an outpatient in appropriate cases. In general, I recommend treatment of 6 months of anticoagulant which is usually Coumadin for most of the time for any DVT that occurs related to immobilization or hospitalization, the things we have mentioned. If it is an idiopathic DVT where it just develops out of the blue this may be a patient who is in amidst of a hypercoagulation workup, they may need to be on it for much longer time and sometimes life long. If it is something very specific such as a upper extremity DVT at the placement of a PICC line, it is probably reasonable to just treat for 3 months and then stop as long as the patient is still not having swelling of symptoms.



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Just a little bit about so called treatment failures. These are in patients who either develop worsening DVTs or a PE, on appropriate heparin or Coumadin therapy on in patients who cannot get the appropriate anticoagulation. This is a picture of inferior vena cava filter and you can see its configuration as designed to lay in the vena cava below the renal veins and to filter the blood and capture blood clots to prevent a PE. That is really its only function. There is lot of confusion, it does not treat DVTs, it does not treat PEs, it is just to stop the clot from coming from the lower legs to the pelvic veins and extending up the vena cava into the lungs. There are permanent filters and otherwise they stay in the body forever and more recently there are temporary filters which generally can stand for 2-3 weeks and then be removed via percutaneous access. These are best in patients who are young and/or people you do not want filtering for long term such as someone who is in a motor vehicle accident cannot receive heparin or Coumadin and who has developed a DVT but will be able to receive the heparin or Coumadin several weeks after he recovers.



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The followup of the DVTs certainly are like any condition you will see in your patient’s office visits fairly frequently or early in the course. Monitoring the INR initially if you are the one managing the Coumadin. This is going to be something done everyday and then eventually every week. There are also good anticoagulation clinics at most hospitals and you can often refer your patients to them for the management. In certain instances repeat ultrasounds may be important in general as I stated before the typical therapy of Coumadin or heparin does not dissolve the clot. So do not necessarily expect the DVT to be gone after 6 months. The reason to get an ultrasound is to identify a treatment failure such as a patient with a clot in the popliteal vein who is on Coumadin and the appropriate therapy and then develops new worse leg swellings and is found to have clot now extending up to common femoral vein. This may be s situation where you would then put a filter in. The other reason is for someone who might have something such as a small clot in one of an unnamed vein in the calf and you want to follow and make sure there is no progression.



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Clearly the reason we are worried about DVTs other than the leg symptoms that may produce chronic changes in the legs and valves that may produce is to prevent a pulmonary embolism. This is the most dreaded complication. About 90% of pulmonary embolisms come from leg veins. They can be silent. In other words, the patient may be doing fine, have no leg symptoms and all of a sudden short of breath. If patients are diagnosed and treated appropriately and aggressively the mortality is less than 10% which means even in the best hands DVTs may develop and these DVTs may lead to PEs. However, the important thing is to identify them quickly and treat them. Obviously, pulmonary embolism, if you are not thinking about it and you miss it and are not treating then the mortalities are exceptionally high.



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This is a CT scan which is a very common way to develop pulmonary embolism and showing clot within the venous pulmonary tree. Other studies that can be useful is a nuclear medicine study called a VQ scan or a ventilation perfusion scan. The idea of this is to see if there are areas in the lung that are ventilated but not perfused which would indicate that this is a normal portion of the lung that is receiving air but there is no blood flow to it which is indicative of a pulmonary embolism. Although this is probably the most common test used over the last 20 years it is falling out of favor in that it can be somewhat inaccurate. Most hospitals are now overlying on CTAs which are rapid and accurate out to about the fourth branch vessels of the pulmonary tree. The other test that is infrequently used but is very accurate and important test which you have at the back of the mind is a pulmonary angiogram that is even more specific and accurate than a CTA. An important thing is ultrasound of the legs is not a surrogate exam for a pulmonary embolism. In other words, in a patient that I described has no leg symptoms, no leg swelling whatsoever and short of breath. If you want to do a simple test which would be an ultrasound of the legs you are not going to find anything almost certainly what you need to do is to focus on where the symptomatology is. So, if the symptomatologies in the leg and ultrasound is a great test if the symptomatology in both the legs in the lung you may be able to find something with the ultrasound. However, if it is just in the lungs doing a leg ultrasound will not make you feel any better.



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Just a word on a condition that can develop in pronounced DVTs, phlegmasia is the _______ term and this is when a leg becomes so swollen from lack of venous outflow that it starts to limit the arterial perfusion and leads to ischemia even though the arteries are open all the way down. The two types of phlegmasia so to speak are phlegmasia cerulea dolens and cerulea albans and these are just depiction of how severe it is when the leg is blue and discolored in the initial phases and then the albans when it is essentially white because it has no arterial flow. These are often surgical emergencies or can potentially be treated with the lytic agents such as TPA or urokinase as I have mentioned on prior slides.

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Another important condition that we know about is what is called the post-phlebitic syndrome. This is in patients who have DVTs with severe damage to their valves and their deep system which result in severe reflux of blood leading to chronic swelling, increased pressure on the skin, and often ulcerations. In fact, if you see a patient who has similar appearance to this and denies to have a family history or personal history of DVT although they may not specifically have a DVT you have to think of that when you are planning their operative plan and what type of preventive therapy you might want to use such as subcutaneous heparin or Venodyne boots, etc. The post-phlebitic syndrome, however, does not have to be as severe as these patients, as I have mentioned. It can just be chronic minor leg swelling. There is also significant amount of pain related to these syndromes and as I have detailed here the ulcers are the final and most severe thing that could be seen in this group of patients.



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This is a quick note on varicose veins. It is probably not in itself in average patient with varicose veins without any inflammations or ulcers. It is not a risk factor. However, it is risk for superficial phlebitis and what that means is clot within the superficial veins now not to believe this not the superficial femoral veins but one of these varicose veins you see here in this picture can develop clot. It is very painful. The leg in that area becomes hard, hot, and red. It is very often to mistake it for a cellulitis and I often see patients who are treated for weeks and weeks of antibiotics when what they have is a superficial phlebitis. An important issue of superficial phlebitis other than the fact that it is very painful and uncomfortable for patients is phlebitis can lead to a DVT by progression and depending on how severe and where in the leg the phlebitis is located you may order an ultrasound to had intervals to make sure there has not been any progression into the deep system.



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Another important point is the greater saphenous vein is a superficial vein. As you know, when there is thrombus in the greater saphenous vein it is much more important than when it is in just one of those varicose veins as depicted in the prior slide and it is still in itself considered superficial phlebitis. It is often identified as a cord in the medial thigh or calf. Some general rules if the thrombus in the saphenous vein is below the knee, most people will follow these patients clinically for worsening symptoms in legs also with serial ultrasounds. If it is high into the thigh especially if it is very near the saphenous femoral junction I often treat these patients just as if they had a DVT since you are essentially splitting hairs you would only be several mm or cm away from the deep vein.



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As I alluded to before sometimes patients will be identified on an ultrasound on having a calf vein DVT. This is as I have mentioned early in the talk often seen in the soleal veins or the gastrocnemius veins or in the posterior tibial veins. In an event in it itself it is not benign. It is still a DVT. Clearly, the more proximal DVTs such as the common femoral iliac veins are more of an impending problem for pulmonary embolism but certainly calf veins can embolize and also calf vein can progress into more proximal DVTs. Depending on patient, it is often safest to treat like a standard DVT however in a very reliable patient with a very small clot burden and a calf vein with no family or personal history of DVT who is going to be mobile you can probably follow by symptoms and ultrasounds.



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Some final comments, as it is clear DVT is a very common condition especially in the perioperative period. Clinicians have to have a very high index of suspicion to diagnose DVT or pulmonary embolism since it is not always classic. The patients do not necessarily have typical findings of swollen legs or rapid onset of shortness of breath. Every time you do a surgery and treat the patient in the hospital or plan some rehabilitation where the patient is not ambulatory, think of prophylaxis.



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It is very important to diagnose these conditions and treat aggressively with heparin. Certainly, if the patient is at excessive risk of bleeding after a major surgery then you may need to place a filter but heparin is the first line therapy you need to be watching for signs of pulmonary embolism and you might need to postpone surgery if a patient has a DVT and needs a foot procedure. If the foot procedure is not urgent, you would certainly want to wait for the 6 months of treatment and allow them to be off the Coumadin for a period of time and follow them clinically before you plan another surgery especially if it is going to lead to prolonged immobilization. I want to thank you for your attention with this lecture.



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In this lecture of venous thromboembolism, background, diagnosis and treatment will be discussed. The viewer should learn about the physiology of thrombosis, which patients are at risk and how DVT's can be prevented. Details on both diagnosis by physical exams and with radiologic testing will be discussed. Finally, the appropriate type and duration of treatment will be covered.
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After participating in this activity, the viewer should be better able to:

1. Know the background and diagnosis of thromboembolic disease.
2. Recall the appropriate type and duration of treatment.
3. Perform an appropriate physical exam.
4. Discuss the physiology

Estimated time to complete this activity is 56 minutes.
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It is the policy of PRESENT e-Learning Systems and it's accreditors to insure balance, independence, objectivity and scientific rigor in all individually sponsored or jointly sponsored educational programs. All faculty participating in any PRESENT e-Learning Systems programs are expected to disclose to the program audience any real or apparent conflict(s) of interest that may have a direct bearing on the subject matter of the continuing education program. This pertains to relationships with pharmaceutical companies, biomedical device manufacturers, or other corporations whose products or services are related to the subject matter of the presentation topic. The intent of this policy is not to prevent a speaker with a potential conflict of interest from making a presentation. It is merely intended that any potential conflict should be identified openly so that the listeners may form their own judgments about the presentation with the full disclosure of the facts.
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Continuing Medical Education

When you register for a Continuing Medical Education ("CME") or a Continuing Education ("CE") activity through our web site, we collect certain personally identifiable information from you such as your name, email address and mailing address. We require that you provide the state in which you are licensed and your license number. In addition to personally identifiable information, we collect aggregated non-personally identifiable information about the activities undertaken by our users. We use the information that we collect through CME/CE activities in several ways:

(i) We are accredited by the Accreditation Council for Continuing Medical Education ("ACCME") to provide continuing medical education for physicians, through a sponsorship agreement with the Mount Sinai School of Medicine. As an ACCME accredited entity, we are required periodically to submit aggregated data about CME participants and the CME activities we certify. We also provide personally identifiable information to other accredited CME/CE providers who certify CME/CE activities posted on our Web sites, as required by the ACCME and other accrediting bodies. These reports may include personally identifiable information about you and credits issued to you, for the purpose of maintaining records that you can request from the accredited provider for up to six (6) years;

(ii) Commercial supporters of CME/CE activities on our Web site will receive only a data about CME/CE activities that are relevant to their interests and/or the courses they support;

(iii) Our Editorial and Customer Support Staff will have internal access to files containing personally identifiable information, including evaluation forms and aggregated CME /CE participant information. These files can be accessed in order to respond to your questions or comments. Our staff may also use personally identifiable information, including registration information and evaluation data, in assessing educational needs and planning marketing activities; and we may use the information we collect as otherwise permitted in this Privacy Policy.

Use of Cookies

Cookies are a technology we use to keep track of users as they move through our Web sites. Your browser allows us to place some information on your computer's hard drive that is associated with the computer you are using. We use cookies to personalize our Web sites and to track your usage across all of our Web sites. Your Web browser can be set to allow you to control whether you will accept cookies, reject cookies, or to notify you each time a cookie is sent to you. If your browser is set to reject cookies, Web sites that are cookie-enabled will not recognize you when you return to the Web site, and some Web site functionality may be lost. The Help section of your browser will tell you how to prevent your browser from accepting cookies.

Although cookies do not normally contain personally identifiable information, if you are a registered user, we may elect to associate your registration information with cookies our Web site places on your computer's hard drive. Associating a cookie with your registration data allows us to offer increased personalization and functionality. For example, you can elect to have our Web sites "remember" your user name and password and bypass the sign-in process on each visit to the site. Without cookies, this functionality would not be possible. Some of our business partners may use cookies on our site (for example, advertisers.) We have told them that we do not want them to use cookie information to track our users' activities once they leave our Web sites. However, because of the way advertisements are served on our Web sites, we do not have total control over how advertisers use cookies on our Web site. If you believe that one of our advertisers is placing an unwanted cookie on your hard drive, please contact privacy officer ( privacy@presentdiabetes.com ) to assist us in resolving the problem.

Uses We Make of Information

In this section of our Privacy Policy, we identify the ways we may use information about you that we have collected.

Aggregate Data

We collect data about visitors to our Web sites for product development and improvement activities. We also use it for market analysis. We may provide information from our Web sites in aggregate form, with identifying information removed, to third parties. For example, we may tell a health care partner what percentage of our registered users are of a particular medical specialty or have certain credentials. Any third party that receives our data must agree not to attempt to re-identify the people it belongs to. For example, we may provide information to a potential advertiser of a product that would appeal to a diabetes patient about what percentage of our users have diabetes. Depending on our agreement with the third parties, we may or may not charge for this information.

Marketing and Advertising

We may target our advertising or marketing depending on information we have about you. For example, a user that is a healthcare professional who treats diabetes may receive advertising for new diabetes therapies (although in neither case will the advertiser have access to any individually identifiable information about you). We may also personalize our Web site based on your interests. For example, you may see different articles in different places on our Web site based on information you have shared with us, or information we have gained by observing your previous behavior, or information we may have gained from your interactions with a third party that shares information with us. We use information for our own internal marketing, research, and related purposes. Third Parties In addition to aggregate information (discussed previously), we may share some kinds of personally identifiable information with third parties as described below.

Other Companies: We have strategic relationships with other companies who offer products and services on our Web sites. When you are interacting with those companies, different rules and privacy policies may apply. We do not control the collection or use of information you provide to these companies, but we do require that those companies clearly state their policies so you can decide whether to give them any information.

Our Employees and Consultants: We contract with other companies and individuals to help us provide services. For example, we may host some of our Web sites on another company's computers, hire technical consultants to maintain our Web-based tools, or work with companies to remove repetitive information from customer lists, analyze data, provide marketing assistance, and provide customer service. In addition, if you are a healthcare professional, we may validate your licensure status and other information against available databases that list licensed health care professionals. In order to perform their jobs, these other companies may have limited access to some of the personal information we maintain about our users. We require all such companies to comply with the terms of our Privacy Policy, to limit their access to any personal information to the minimum necessary to perform their obligations, and not to use the information they may access for purposes other than fulfilling their responsibilities to us. We use our best efforts to limit the use of other companies in areas where personally identifiable information may be involved.

Promotional Offers: Sometimes we send offers to selected groups of customers on behalf of other businesses. When we do this, we do not give that business your name and address. We provide a variety of mechanisms for you to tell us you do not want to receive such promotional offers. For example, we may provide an opt-in box for consumers to receive an email from another business, and we make clear that by opting in you are submitting your data to a third party.

Protection of Information

In this section of our Privacy Policy, we discuss the security measures we take to protect information that we have collected about you.

We have implemented technology and security policies, rules and other measures to protect the personal data that we have under our control from unauthorized access, improper use, alteration, unlawful or accidental destruction, and accidental loss. We also protect your information by requiring that all our employees and others who have access to or are associated with the processing of your data respect your confidentiality. We use security methods to determine the identity of its registered users, so that appropriate rights and restrictions can be enforced for that user. Reliable verification of user identity is called authentication. We use both passwords and usernames, as well as double opt-n verification, to authenticate users. Users are responsible for maintaining their own passwords.

Access to Information and Choices

In this section of our Privacy Policy, we tell you how to obtain and correct information we have about you, and how to choose what types of information you may share with us.

Correction of Information We Have About You

If you believe that registration information collected by our Web site(s) is in error, you may edit your personal profile any time that you like. You can directly edit most of your user profile on the Web site on which you initially registered. Information that you can not edit may only be changed by contacting Web Customer Support (see CONTACTS). Requests for deletion of your record may result in your removal from the registry, but we may keep certain demographic information about you for product improvement purposes. You may contact Web Customer Support and ask for the changes that you would like to make.

Our Employees

Our employees are required to keep customer information private, as a condition of their employment with the company. Only selected, authorized employees are permitted to access personal information. Our employees with access to personally identifiable information are required to attend a confidentiality/privacy training class, and to sign a confidentiality agreement. All employees and contractors must abide by our Privacy Policy, and those who violate that policy are subject to disciplinary action, up to and including termination of their employment and legal action.
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