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Query: UMLS:C0034065 (pulmonary embolism)
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Venous thromboembolic disease (deep vein thrombosis and pulmonary embolism) are common disorders with serious morbid and mortal complications. Given the varied modes of presentation, a high clinical index of suspicion in patients at risk must exist among physicians. Standard therapy has consisted of intravenous unfractionated heparin and overlapping administration of an oral Vitamin K antagonist, commonly Warfarin. Although an effective strategy, many practical limitations exist, including the need for prolonged hospitalization, frequent laboratory monitoring for anticoagulant effect, and erratic dose-response curves. Recently, subcutaneous low-molecular-weight heparins have emerged as safe and effective alternatives for unfractionated heparin. Appropriate patients may be treated with low-molecular-weight heparins and oral Warfarin entirely as outpatients, with similar efficacy and risk of recurrent thromboembolic events and hemorrhage. Thrombolytic therapy is a reasonable alternative in patients with iliofemoral venous thrombosis and/or pulmonary embolism resulting in hemodynamic compromise or obstructing significant pulmonary vasculature. Risks of serious hemorrhagic side effects including intracranial hemorrhage, along with the added economic burden, have limited widespread acceptance of thrombolytic therapy as primary treatment. Emerging oral direct thrombin inhibitors and other novel agents stand to move the treatment of patients with venous thromboemboli to even greater levels of safety and efficacy.
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PMID:Medical management of venous thromboembolic disease. 1525 62

Every year, approximately 2 million people experience a deep venous thrombosis (DVT). Approximately 600,000 of these people are diagnosed with a pulmonary embolism and about 10% of these die. It has been established that surgery, anesthesia, and bed rest increase the risk of DVT, and therefore, patients who undergo a major lower-extremity procedure should receive prophylaxis. During the past 10 years, the choices of pharmacological and mechanical prophylaxis have increased greatly. Warfarin is probably the most widely used prophylactic method in the U.S., but low-molecular-weight heparin (LMWH) use has increased. Also available is a synthetic pentasaccharide that acts as an anti-Xa inhibitor to decrease DVT without increase in bleeding. All but warfarin are given by subcutaneous injection and require no laboratory management to adjust the medication. Another drug in clinical trials is a direct thrombin inhibitor taken orally in a fixed dose that does not require monitoring. Non-pharmacological prophylaxis and/or stacked modalities, although used, have not shown the efficacy of pharmacological prophylaxis. With the incidence of DVT reported in the range of 41% to 85% without prophylaxis in joint replacement and hip-fracture surgery, prophylaxis is warranted in all lower-extremity joint replacement and hip-fracture patients.
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PMID:Advances in DVT prophylaxis and management in major orthopaedic surgery. 1545 36

The surgical management of patients on anticoagulant therapy is often poorly understood in all fields of medicine (not just dentistry). Until now there has been no uniform approach to managing these patients and much of the advice routinely given by medical practitioners and haematologists has fallen behind the recent evidence. Many medical conditions from atrial fibrillation to prosthetic heart valves predispose patients to venous thrombosis and pulmonary embolism (Table 1). In order to prevent these complications, these patients are normally placed on an anticoagulant. By far the most common one in use is Warfarin, which is a derivative of 4 hydroxycoumarin.
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PMID:Management of dental patients on warfarin therapy in a primary care setting. 1565 77

Pulmonary embolism (PE) is a major health problem. Mortality in untreated PE is high, but with adequate (anticoagulant) treatment, can be reduced. Multiple primary and secondary risk factors are responsible for PE. But there is rare association of mixed adrenal tumor with PE. Here, we report a case of adrenocortical adenoma with Cushing's syndrome coexistent with pheochromocytoma with recurrent PE in an elderly patient with prostate adenocarcinoma. A 78-year-old Taiwanese retired veteran was admitted in July, 2002 with the presentation of syncope. Three years before, he was diagnosed with prostate adenocarcinoma and had received Androcur therapy since then. Five months later, he was admitted with Cushingoid appearance and hypertension. Abdominal imaging studies revealed a left adrenal tumor. Laparoscopic adrenalectomy revealed an adrenocortical adenoma. Two years later, a recurrent left adrenal tumor was found. Repeated laparoscopic adrenalectomy revealed pheochromocytoma. One month after the repeat laparoscopic surgery, the patient was admitted due to syncope. Chest X-ray revealed cardiomegaly with pulmonary venous congestion. Echocardiogram showed impaired right ventricle global systolic function. Perfusion lung scan showed a high probability of PE. Heparin and coumadin were given but stopped 5 weeks later due to the development of severe skin ecchymosis. In December 2002, the patient was admitted again with consciousness disturbance. Chest computed tomography (CT) revealed bilateral PE, and he died 5 hours later due to cardiogenic shock. In conclusion, in elderly patients with Cushing's syndrome with pheochromocytoma and prostate carcinoma, there is probability of pulmonary embolism.
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PMID:Recurrent pulmonary embolism in an elderly patient with Cushing's syndrome, adrenocortical adenoma, pheochromocytoma and prostate adenocarcinoma. 1551 Sep 34

Patients who undergo orthopaedic surgery are at substantially increased risk for venous thromboembolic events. These include proximal and distal deep vein thrombosis, with the former more likely to lead to pulmonary embolism and fatal complications. Anticoagulants are routinely used for venous thromboembolism prophylaxis in patients undergoing total hip or total knee replacement surgery. Although current treatments offer effective prophylaxis, they have disadvantages. Warfarin is limited by the requirement for coagulation monitoring to ensure effective and safe use. Similarly, low-molecular-weight heparins (LMWHs) have disadvantages, including the need for parenteral administration. This article brings together data from clinical trials of the novel oral direct thrombin inhibitor, ximelagatran, in the prevention of venous thromboembolism in patients undergoing elective total hip or total knee replacement. The ximelagatran clinical trial programme in orthopaedic surgery has focused primarily on five large multicentre studies in Europe (the Melagatran Thromboprophylaxis in Orthopaedic surgery II and III and Expanded Prophylaxis Evaluation Surgery Study studies) and in the United States (the Exanta Used to Lessen Thrombosis A and B studies), which enrolled more than 8000 patients. In addition, the USA clinical trial programme included three other trials that investigated ximelagatran in orthopaedic surgery; two of these studies focused on prevention of venous thromboembolism after total knee replacement, and one study investigated prevention of venous thromboembolism after total hip replacement. These studies compared ximelagatran with the LMWHs dalteparin and enoxaparin and with warfarin, and were designed to reflect regional differences in venous thromboembolism prophylaxis and to build on findings from previous studies. Generally, ximelagatran has been shown to possess comparable or greater efficacy relative to comparators. The timing and dose of ximelagatran have been shown to be important determinants of its efficacy and safety. As ximelagatran can be given in fixed oral dosing without coagulation monitoring, it is an attractive choice for the prevention of venous thromboembolism in major elective orthopaedic surgery.
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PMID:Clinical experience with ximelagatran in orthopaedic surgery. 1558 25

Venous thromboembolism, which is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE), represents a significant cause of death, disability, and discomfort. Two million people/year are affected by VTE, making it the third most common cardiovascular disease after coronary heart disease and stroke. The rationale for VTE prophylaxis stems from the clinically silent presentation of the disease and its prevalence among hospitalized patients. At greatest risk are patients undergoing major orthopedic surgery and those admitted to the intensive care unit with acute myocardial infarction, heart failure, ischemic stroke, respiratory disease, systemic infection, or other medical conditions that immobilize patients for 5 days or longer. Several anticoagulant regimens have been effective in reducing the risk of VTE after major orthopedic surgery. For patients undergoing total hip or knee replacement, treatment with adjusted-dose warfarin, low-molecular-weight heparins, or fondaparinux may be used. Warfarin, which has been around for more than 50 years, is the only oral anticoagulant available for VTE prophylaxis. Ximelagatran, a new low-molecular-weight oral prodrug of the direct thrombin inhibitor melagatran, has advantages over warfarin that may make it the drug of choice for prevention of VTE.
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PMID:The role of oral direct thrombin inhibitors in the prophylaxis of venous thromboembolism. 1562 37

New treatment strategies based on the availability of alternative anticoagulants have improved outcomes for patients with heparin-induced thrombocytopenia (HIT). Patients with HIT are at an extreme risk of thrombosis even after the discontinuation of heparin. Maintaining a high degree of awareness and instituting alternative anticoagulation immediately on suspicion of HIT are the two keys to preventing death, limb amputation, and other complications such as pulmonary embolism, myocardial infarction, or stroke; stopping heparin alone is inadequate. Warfarin should not be used early or unopposed with HIT, and when appropriate, transition to warfarin must be done cautiously to avoid venous limb gangrene or central skin necrosis. The direct thrombin inhibitors (DTIs) lepirudin and argatroban are approved by the US Food and Drug Administration for treating HIT and both are effective for improving patient outcomes. Because of its favorable pharmacologic characteristics, the DTI bivalirudin has been successfully employed in HIT, particularly in patients with multiorgan failure.
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PMID:Evolving management strategies for heparin-induced thrombocytopenia. 1610 54

Patients undergoing major lower-extremity orthopedic surgery such as total hip replacement (THR) and total knee replacement (TKR) are at an increased risk of venous thromboembolism (VTE). Routine prophylaxis is necessary to reduce the risk of deep vein thrombosis (DVT), which may progress to potentially fatal pulmonary embolism and secondary complications such as postthrombotic syndrome, recurrent DVT, and chronic pulmonary hypertension. Prophylaxis in patients undergoing TKR, THR, and hip fracture surgery is now standard practice and generally involves anticoagulant treatment with either low-molecular-weight heparin (LMWH) or warfarin for a period of 7 to 10 days, with extended prophylaxis in those with ongoing risk factors such as obesity, cancer, or previous VTE. Data from clinical practice suggest that there is a general trend toward longer postsurgical prophylaxis and shorter hospital stays, making practicality of treatment an important consideration. LMWH is effective for the prophylaxis of VTE, but the parenteral route of administration is not convenient for use in the outpatient setting. Warfarin, on the other hand, can be administered orally but requires the infrastructure for careful patient monitoring and dose adjustments because of its unpredictable dose-response relationship. The development of new anticoagulants has been pursued with the aim of improving efficacy, predictability, consistency of response, safety, and convenience. A recently approved anticoagulant, fondaparinux, has been proven to provide superior efficacy for the prevention of VTE compared with LMWH, but this agent requires parenteral administration and does not overcome the convenience issue. Ximelagatran is the oral form of the direct thrombin inhibitor melagatran, which is available for subcutaneous administration. Ximelagatran has a consistent anticoagulant response allowing fixed oral dosing without the need for coagulation monitoring. The efficacy and safety profile of melagatran/ximelagatran prophylaxis for VTE following THR and TKR has compared favorably with standard LMWH prophylaxis, as seen in the European METHRO II and III trials and EXPRESS trial, and with warfarin prophylaxis, as seen in the North American EXULT A and B trials. Several prophylactic treatment regimens have been evaluated in the European trials to determine the optimal dosing and timing of first dose of melagatran to achieve the best balance of efficacy and safety. Preoperative initiation of melagatran was more effective than when prophylactic treatment was initiated postoperatively, and the lowest rates of bleeding were associated with a postoperative initiation of prophylaxis. Early administration of the first postoperative melagatran dose (4 to 8 hours) was also associated with better prophylactic efficacy relative to a later postoperative start (8 to 12 hours). The results of the comprehensive international clinical trial program and in particular the optimal balance of efficacy/safety data provided by the METHRO III study have led to approval of melagatran/ximelagatran in 2004 in the European Union for the prevention of VTE in patients undergoing elective hip or knee replacement surgery. Ximelagatran has the potential to maximize the use of anticoagulation in patients discharged following major lower-extremity orthopedic surgery.
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PMID:Ximelagatran for the prevention of venous thromboembolism following elective hip or knee replacement surgery. 1612 14

Venous thromboembolism (VTE), which is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE), represents a significant cause of death, disability, and discomfort. They are frequent complications of various surgical procedures. The aging population and the survival of more severely injured patients may suggest an increasing risk of thromboembolism in the trauma patients. Expanded understanding of the population at risk challenges physicians to carefully examine risk factors for VTE to identify high-risk patients who can benefit from prophylaxis. An accurate knowledge of evidence-based risk factors is important in predicting and preventing postoperative DVT, and can be incorporated into a decision support system for appropriate thromboprophylaxis use. Standard use of DVT prophylaxis in a high-risk trauma population leads to a low incidence of DVT. The incidence of VTE is common in Asia. The evaluation includes laboratory tests, Doppler test and phlebography. Screening Doppler sonography should be performed for surveillance on all critically injured patients to identify DVT. D-Dimer is a useful marker to monitor prophylaxis in trauma surgery patients. The optimal time to start prophylaxis is between 2 hours before and 10 hours after surgery, but the risk of PE continues for several weeks. Thromboprophylaxis includes graduated compression stockings and anticoagulants for prophylaxis. Anticoagulants include Warfarin, which belongs to Vitamin K antagonists, unfractionated heparin, low molecular weight heparins, factor Xa indirect inhibitor Fondaparinux, and the oral IIa inhibitor Melagatran and ximelagatran. Recombinant human soluble thrombomodulin is a new and highly effective antithrombotic agent. Prophylactic placement of vena caval filters in selected trauma patients may decrease the incidence of PE. The indications for prophylactic inferior vena cava filter insertion include prolonged immobilization with multiple injuries, closed head injury, pelvic fracture, spine fracture, multiple long bone fracture, and attending discretion. Multiple-trauma patients are at increased risk for DVT but are also at increased risk of bleeding, and the use of heparin may be contraindicated. Serial compression devices (SCDs) are an alternative for DVT prophylaxis. Compression devices provide adequate DVT prophylaxis with a low failure rate and no device-related complications. Immobilization is one of important reasons of VTE. The ambulant patient is far less likely to develop complications of inactivity, not only venous thrombosis, but also contractures, decubitus ulcers, or osteoporosis (with its associated fatigue fractures), as well as bowel or bladder complications.
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PMID:Prophylaxis against venous thromboembolism in orthopedic surgery. 1684

The purpose of this study was to determine the incidence of deep venous thrombosis in medical intensive care unit patients receiving deep venous thrombosis prophylaxis. This was a prospective cohort study of 141 consecutive adult patients anticipated to remain in the medical intensive care unit for >48 hours. Deep venous thrombosis prophylaxis was provided using subcutaneous unfractionated heparin or a sequential compression device according to risk-stratified protocol. Compression ultrasound was performed. Fourteen patients (9.9%) developed deep venous thrombosis on follow-up studies. Incidence of deep venous thrombosis was 7.9% per person year (95% confidence interval, 4.8-12.8). Two of 14 developed pulmonary embolism. Eight patients required full anticoagulation with intravenous heparin or coumadin. In-hospital mortality was similar in both groups. Patients with deep venous thrombosis had a statistically higher risk of pulmonary embolism: 14.2% (95% confidence interval, 2.0-43.0) versus 0.0% (95% confidence interval, 0-3; P = .009). Incidence of deep venous thrombosis is high in medical intensive care unit patients receiving standard prophylaxis. Adherence to strict deep venous thrombosis prophylaxis protocol and exploration of other prophylaxis regimens should be pursued.
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PMID:Efficacy of deep venous thrombosis prophylaxis in the medical intensive care unit. 1709 99


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