Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular disease is the major cause of mortality in the industrial world today. We are constantly moving towards new and better ways of fighting this epidemic. Advances have been made in various fields such as patient education, imaging techniques, interventional cardiology, and novel therapeutic agents. In particular, antithrombotics are being studied with great interest and hope. Amid this class of agents, factor Xa inhibitors have already begun to show promising results in trials involving patients with acute coronary syndromes. Whereas DX-9065a is in late stage clinical trials, fondaparinux sodium is available for clinical use. Promising results have been obtained with fondaparinux sodium in patients with coronary artery disease in the PENTUA (Pentasaccharide in Unstable Angina) and PENTALYSE (Pentasaccharide as an Adjunct to Fibrinolysis in ST-Elevation Acute Myocardial Infarction) trials. Besides having a direct effect on the coagulation cascade, they have shown properties that indirectly influence the remodeling of plaques in the coronary circulation. Available evidence on factor Xa inhibitors does not ensure a remedy to acute coronary syndromes but it gives hope of improving current treatments and reducing the morbidity and mortality of cardiovascular disease. The efficacy and tolerability of fondaparinux sodium in the prevention and treatment of deep vein thrombosis (with or without pulmonary embolism) has been established in several large trials such as PENTATHLON (Pentasaccharide in Total Hip Replacement Surgery), PENTAMAKS (Pentasaccharide in Major Knee Surgery), EPHESUS (European Pentasaccharide Hip Elective Surgery), PENTHIFRA (Pentasaccharide in Hip-Fracture Surgery), and PENTHIFRA-Plus. Whereas fondaparinux sodium offers benefits over low molecular weight heparins and unfractionated heparin, the incidence of bleeding complications was greater with fondaparinux sodium than with unfractionated heparin. Treatment with factor VIIa can reverse the anticoagulant effect of fondaparinux sodium and this may be particularly important in patients who need to undergo emergency surgical procedures. Fondaparinux sodium has been recently approved for use, in conjunction with warfarin, in patients with symptomatic deep vein thrombosis or acute pulmonary embolism based on the results of two large trials conducted by the Matisse investigators. In conclusion, these observations strongly suggest the clinical potential of this class of agents in preventing arterial and venous thrombosis.
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PMID:Clinical and experimental experience with factor Xa inhibitors. 1555 23

Venous thromboembolism (VTE), a highly prevalent vascular disorder, is frequently clinically silent, and is often difficult to diagnose. VTE consists of both deep vein thrombosis (DVT) and pulmonary embolism (PE), both of which are associated with potentially significant morbidity and mortality. With the availability of safe and effective antithrombotic therapy, the standard of medical care should be the routine use of thromboprophylaxis. The risk of developing VTE increases with advancing age, and the performance of surgery to repair a fractured hip increases this risk even more. Thus elderly hip fracture patients are always considered to be at the highest risk for developing fatal PE. Over the last decade, new anticoagulants, such as the factor Xa inhibitor fondaparinux, have been developed that specifically target individual components of the coagulation system. Fondaparinux is a selective, synthetic factor Xa inhibitor that has been shown to significantly reduce the risk of VTE versus enoxaparin in patients undergoing surgery for hip fracture. Extended (4-week) prophylaxis with fondaparinux can produce a 96% reduction in risk of DVT and an 89% reduction in risk of symptomatic VTE events relative to perioperative (1-week) prophylaxis. As the only anticoagulant approved in the United States for thromboprophylaxis in hip fracture patients, fondaparinux offers more effective prophylaxis against VTE without compromising safety.
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PMID:Hip fracture and venous thromboembolism in the elderly. 1555 89

Venous thromboembolism, which includes deep vein thrombosis and pulmonary embolism, is the result of an imbalance among procoagulant, anticoagulant and profibrinolytic processes. This imbalance reflects a complex interplay between genetic and environmental or acquired risk factors. Genetic thrombophilic defects influence the risk of a first episode of thrombosis. How these defects influence the risk of recurrence in patients whose first episode of venous thromboembolism was unprovoked is less certain. Thus, when anticoagulants are stopped, patients with unprovoked venous thromboembolism have a risk of recurrence of at least 7% to 10% per year, even in the absence of an underlying thrombophilic defect. Consequently, there is a trend toward longer durations of anticoagulation therapy for these patients, which is problematic given the limitation of existing anticoagulants. This chapter provides an overview of the thrombophilic defects and how they influence the risk of venous thromboembolism. The chapter also details advances in anticoagulant therapy, focusing on new inhibitors of factor Xa and thrombin. In Section I, Dr. Saskia Middeldorp describes the various thrombophilic defects and reviews their relative importance in the pathogenesis of a first episode of venous thromboembolism. She then discusses the influence of these defects on the risk of recurrent thrombotic events in patients with unprovoked venous thromboembolism and in those whose thrombosis occurred in association with a known risk factor, such as surgery. In Section II, Dr. William Geerts reviews the pharmacology of new parenteral and oral factor Xa inhibitors and describes the results of the Phase II and III clinical trials with these agents. He then provides perspective on the potential advantages and drawbacks of these drugs for the prevention and treatment of venous thromboembolism. In Section III, Dr. John Heit focuses on direct thrombin inhibitors. He discusses their mechanism of action and compares and contrasts their pharmacological profiles prior to describing the results of Phase II and III clinical trials. Dr. Heit then provides perspective on the potential advantages and limitations of these drugs relative to existing anticoagulants.
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PMID:Thrombophilia and new anticoagulant drugs. 1556 96

We have studied the physiological effects of DX-9065a, a selective factor Xa (FXa) inhibitor, and heparin in experimental venous thrombus and acute pulmonary embolism. Moreover, the effects of these compounds were also evaluated under the condition of plasminogen activator inhibitor-1 (PAI-1) deficiency. A thrombus was induced in the murine femoral vein. The compounds prolonged the time to occlusion in a dose-dependent manner. Pulmonary embolism was induced by continuous induction of venous thrombi in the left jugular vein. The mortality of mice increased time-dependently. Histological evidence of thromboembolism in the lung was obtained in all mice. Treatment with DX-9065a, but not heparin, reduced the mortality at 6 h after initiation of venous thrombi. In separate experiments, pulmonary thromboembolism was induced in PAI-1 knockout mice. The mortality in PAI-1 knockout mice was reduced compared with that of wild-type mice. Moreover, when DX- 9065a was administered to PAI-1 knockout mice with pulmonary thromboembolism, mice survived well without marked bleeding. These findings indicate that the dual inhibition of coagulation FXa and PAI-1 could be beneficial in the treatment of acute pulmonary embolism.
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PMID:Lack of plasminogen activator inhibitor-1 enhances the preventive effect of DX-9065a, a selective factor Xa inhibitor, on venous thrombus and acute pulmonary embolism in mice. 1558 51

Fondaparinux (Arixtra) is the first selective factor Xa inhibitor approved for use in thromboprophylaxis after orthopaedic surgery. New recently completed trials have also demonstrated the potential of fondaparinux in the prevention of venous thromboembolism (VTE) in other surgical and medical settings and in the treatment of established VTE. In the randomized double-blind PEGASUS study in high-risk abdominal surgery patients, fondaparinux reduced the incidence of VTE from 6.1% with dalteparin to 4.6% (odds ratio reduction = 25.8%, P = 0.14), without increasing the bleeding risk. In the randomized double-blind ARTEMIS trial in acutely ill medical patients, fondaparinux reduced the incidence of VTE from 10.5% with placebo to 5.6% (odds ratio reduction = 49.5%, P = 0.029), without increasing the bleeding risk; there was no pulmonary embolism in the fondaparinux group compared with five, all fatal, in the placebo group (P = 0.029). In the two MATISSE trials, both the efficacy and safety of once daily fondaparinux were at least as good as enoxaparin in the treatment of deep-vein thrombosis (MATISSE-DVT) and unfractionated heparin in the treatment of pulmonary embolism (MATISSE-PE). In patients with coronary artery disease, promising results were obtained in phase II trials and large phase III trials are ongoing. In conclusion, fondaparinux may further improve and simplify the prevention and treatment of thrombosis in a large range of medical and surgical settings.
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PMID:Fondaparinux: an update on new study results. 1570 Nov 45

Anticoagulation therapy with unfractionated heparin, low-molecular-weight heparins and oral vitamin K antagonists is currently the mainstay of treatment and prevention of thromboembolic disorders (such as deep vein thrombosis, pulmonary embolism and stroke prevention in patients with atrial fibrillation). Although these therapies have proven benefits, they also have important limitations that result in their underuse in routine clinical practice. Consequently, many patients identified by guidelines as requiring anticoagulant therapy receive no or inadequate treatment. Heparins require parenteral administration and pose the risk of heparin-induced thrombocytopenia. Vitamin K antagonists have a narrow separation of antithrombotic and haemorrhagic effects and numerous food and drug-drug interactions, and require frequent coagulation monitoring and dose adjustment to ensure effective antithrombotic protection while minimizing the risk of bleeding complications. In response to these limitations, several new anticoagulants have recently been developed, including selective factor Xa inhibitors such as fondaparinux and ximelagatran, the first oral agent in the new class of direct thrombin inhibitors and the first new oral anticoagulant for almost 60 years. Ximelagatran possesses many of the properties of an ideal agent for anticoagulation therapy. With its oral formulation, consistent and predictable pharmacological profile and no coagulation monitoring, ximelagatran has the potential to increase the use and duration of anticoagulation treatment in thromboembolic disorders and to reduce the burden associated with long-term management.
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PMID:Current issues in anticoagulation. 1581 98

Venous thromboembolism (VTE) remains a significant cause of morbidity and mortality in hospitalized patients with acute medical illness. The high prevalence of VTE in this patient population, its clinically silent nature, and associated morbidity and mortality indicate that prophylactic therapy is appropriate in those determined to be at increased risk. Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) have been shown to reduce the incidence of VTE and are the primary therapies used for prophylaxis in these patients. Although both UFH and LMWH have received grade 1A recommendations for the prevention of VTE in at-risk medical patients in the 2004 American College of Chest Physicians consensus conference statements, LMWH has advantages over UFH in its once-daily dosing scheme, reduced incidence of major and minor bleeding events, and reduced incidence of heparin-induced thrombocytopenia. Fondaparinux is a novel antithrombotic agent characterized by specificity for factor Xa and a lack of platelet interaction. A recent clinical trial in hospitalized patients with acute medical illness found that fondaparinux significantly reduced the incidence of both VTE and fatal pulmonary embolism compared with placebo, without increased major bleeding. Despite the availability of effective thromboprophylactic therapies, VTE prophylaxis continues to be underutilized in hospitalized medical patients.
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PMID:Emerging strategies in the prevention of venous thromboembolism in hospitalized medical patients. 1610 Jan 92

Venous thromboembolism (VTE), a prevalent, costly medical condition, is one of the most common causes of death in the United States. Although risk factors for VTE are well known, thromboembolic events cannot be predicted because patients are asymptomatic and screening methods have limitations. Anticoagulant therapy (eg, low-molecular-weight heparin, unfractionated heparin, selective factor Xa inhibitors) has proved effective for preventing thromboembolism, including deep vein thrombosis and pulmonary embolism. While quality care for VTE entails prophylaxis for all relevant patients, many high-risk patients are undertreated or treated incorrectly. Both primary and secondary prevention of VTE remain inadequate for several reasons, including lack of awareness of the American College of Chest Physicians guidelines, of the seriousness of VTE, of the benefits of prophylaxis, and of the relatively low risk of bleeding complications. To provide appropriate treatment, physicians must assess the numbers and types of risk factors for each patient, the underlying illness or surgical procedure, and the benefits and risks of possible therapies. The problem of VTE will grow as the US population ages, as surgery is performed on increasingly sick patients, and as the length of hospital stays continues to decrease.
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PMID:Venous thromboembolism prophylaxis guidelines: use by primary care physicians. 1675 50

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

Anticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). Such treatment is divided into two stages. Rapid initial anticoagulation is given to minimize the risk of thrombus extension and fatal pulmonary embolism, whereas extended anticoagulation is aimed at preventing recurrent VTE, thereby reducing the risk of postphlebitic syndrome. With currently available drugs, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists, such as warfarin. Emerging anticoagulants have the potential to streamline VTE treatment. These agents include idraparinux, a long-acting synthetic pentasaccharide that is given subcutaneously on a once-weekly basis, and new oral anticoagulants that target thrombin or factor Xa. This paper i) reviews the pharmacology of these agents, ii) outlines their potential strengths and weaknesses, iii) describes the results of clinical trials with these new drugs, and iv) identifies the evolving role of new anticoagulants in the management of VTE.
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PMID:Emerging anticoagulants for the treatment of venous thromboembolism. 1695 67


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