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)

In this randomized, multicenter, controlled, double-blind, sequential trial, 381 patients undergoing primary total knee replacement were randomly assigned to receive subcutaneous injections of either 3500 IU anti-factor Xa of bemiparin sodium, first dose 6 h after surgery, or 40 mg of enoxaparin, first dose 12 h before surgery, followed by daily doses for 10 +/- 2 days, for the prophylaxis of venous thromboembolism. The primary efficacy endpoint was venous thromboembolism up to postoperative day 10 +/- 2, defined as deep vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep vein thrombosis and/or documented symptomatic pulmonary embolism. The primary safety endpoint was major bleeding. Eighty-seven percent of all randomized patients (333 of 381 patients) were evaluable for efficacy. The incidence of venous thromboembolism was 32.1% (53 of 165 patients) in the bemiparin group and 36.9% (62 of 168 patients) in the enoxaparin group. The absolute risk difference was 4.8% in favor of bemiparin [95% confidence interval (CI), -15.1% to 5.6%; non-inferiority P-value: 0.02; superiority P-value: 0.36]. The incidence of proximal deep vein thrombosis was 1.8% (three of 165 patients) in the bemiparin group and 4.2% (seven of 168 patients) in the enoxaparin group. Major bleeding occurred in six patients (three in each group). There were no deaths during the study. This trial shows that bemiparin started postoperatively is as effective and safe as enoxaparin started preoperatively in the prevention of venous thromboembolism in patients undergoing total knee replacement.
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PMID:Efficacy and safety of bemiparin compared with enoxaparin in the prevention of venous thromboembolism after total knee arthroplasty: a randomized, double-blind clinical trial. 1287 40

Unfractionated heparin, low molecular weight heparin and vitamin K antagonists are anticoagulants currently used for the prevention and treatment of deep vein thrombosis and pulmonary embolism. Considerable limitations of these agents, such as a narrow therapeutic window, a variable dose response or lack of oral bioavailability, created the need for new anticoagulants. Numerous new compounds with different mechanisms of action have been developed and some have been already approved for clinical use. Quite recently, fondaparinux, an indirect anti-factor Xa inhibitor, has been licensed in Europe and in the US for prevention of VTE in patients undergoing hip or knee replacement surgery. In addition, lepirudin, a recombinant hirudin derivative, and the heparinoid danaparoid, have been approved in Austria for treatment of heparin-induced thrombocytopenia. Recombinant nematode anticoagulant protein c2, the orally available thrombin inhibitor ximelagatran and ART-123, a recombinant soluble thrombomodulin, are in advanced stages of clinical development. This article reviews mechanisms and sites of action, and the current state of preclinical and clinical research of these and various other agents with respect to the prevention and treatment of venous thromboembolism).
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PMID:Novel anticoagulants for the prevention and treatment of venous thromboembolism. 1464 23

Despite widespread use of antithrombotic agents, major orthopedic surgery (total hip arthroplasty, major knee surgery, fracture of the femoral neck) still raises a high risk of deep vein thrombosis and pulmonary embolism. Proper understanding of thromboprophylaxis in orthopedic surgery requires good knowledge of the mechanisms of coagulation and the point of action of different antithrombotic agents. Sodium fondaparinux is the first synthetic inhibitor selective for factor Xa. It is composed of five saccharide units obtained by chemical synthesis, thus eliminating the risk of contamination by a pathogenic agent of animal origin and batch variability. Clinical trials using sodium fondaparinux for the prevention of venous thromboembolism after major orthopedic surgery have demonstrated its superiority over low-molecular-weight heparin without increased risk of clinically pertinent bleeding if the first injection is given at the proper time. We present the main results of clinical trials.
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PMID:[Prevention of venous thromboembolism after major orthopedic surgery: update and contribution of a specific synthetic inhibitor of factor Xa]. 1472 38

Enoxaparin (enoxaparin sodium) is a low-molecular-weight heparin that binds to and increases the activity of antithrombin III. The resulting complex inhibits prothrombinase-mediated thrombin generation and direct thrombin generation by binding to factor Xa and thrombin factor IIa. Enoxaparin, used as prophylaxis in medically ill patients at increased risk for thromboembolism, has shown significantly increased efficacy compared with placebo in reducing the incidence of deep vein thrombosis and pulmonary embolism. Indeed, 291 patients receiving subcutaneous enoxaparin 40 mg/day had a frequency of venous thromboembolism of 5.5% during 14 days of treatment, whereas 14.9% of the 288 placebo recipients experienced thromboemboli (p < 0.001). There was no reduction in the incidence of thromboembolism in the 287 recipients of enoxaparin 20 mg/day (15%). In other studies, prophylactic treatment for 7 days with subcutaneous enoxaparin 40 mg/day was at least as effective as unfractionated heparin in reducing the frequency of venous thromboembolism in 959 nonsurgical patients at increased risk for deep vein thrombosis and pulmonary embolism (total incidence = 0.2 and 1.4%, respectively). Moreover, enoxaparin recipients experienced fewer adverse events than did heparin recipients. The most frequent adverse events reported in medically ill and surgical patients receiving enoxaparin 40 mg/day were hemorrhage (17.4 vs 14.3% for placebo), hematoma at injection site, anemia, fever, peripheral edema, nausea, ecchymosis and edema (unspecified site).
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PMID:Enoxaparin: in the prevention of venous thromboembolism in medical patients. 1472 9

Pulmonary embolism as a part of venous thromboembolic disease has a broad spectrum of clinical presentations from minimal disease to life-threatening right heart failure. Therapy has to be guided by the risk associated with the individual clinical state of the patient. As long as hemodynamics are entirely stable, anticoagulation is given in order to prevent early or late recurrence, thereby allowing for endogeneous thrombolysis and recovery. In hemodynamically instable patients, i.e. patients under cardiopulmonary resuscitation or in shock, there is the need for a rapid reduction of thrombus mass in order to restore right ventricular function. Systemic thrombolysis is the most feasible modality to reduce the thrombus burden of the pulmonary circulation in the short term. For hemodynamically stable patients with right ventricular dysfunction as assessed by echocardiography, there is still some controversy as to whether thrombolysis improves the long-term outcome. At the least, thrombolysis may positively modify the short-term course of acute disease in patients with an extremely low risk of bleeding. When the acute phase has been overcome, secondary prophylaxis with vitamin K antagonists has to be given. The duration of secondary prophylaxis requires an individual assessment of both the risk of recurrence and the risk of bleeding. In the near future, new anticoagulant drugs such as direct thrombin and factor Xa inhibitors will offer new treatment modalities for the acute phase as well as for secondary prophylaxis.
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PMID:New therapeutic approaches in pulmonary embolism. 1473 83

We illustrate a strategy for developing an antithrombotic agent based on the low-molecular-weight heparin (LMWH) tinzaparin experience. After anti-factor Xa and IIa activity pharmacokinetic characterization in healthy volunteers, clinical studies first explored the doses and then confirmed thrombosis prevention effects in postoperative (general and hip or knee replacement surgery) settings as compared with placebo and active treatments. This experience and additional dose-finding assessments led to large clinical studies verifying the effectiveness of tinzaparin in the treatment of deep vein thrombosis and acute pulmonary embolism. Subgroup analyses from these studies and preclinical experiments suggested a role for tinzaparin in patients with malignancy who are at high risk for thromboembolic complications. Challenging patient populations and other thrombotic disorders spawned interest in tinzaparin studies in the obese, the hemodialysis, the stroke, peripheral angioplasty, and the pregnant patient as well as in children with thromboembolic disorders. New therapeutic challenges were addressed with a bridging study for patients requiring interruption of oral anticoagulant therapy, a study of patients undergoing cardioversion for atrial fibrillation, and outpatient venous thromboembolism treatment studies. Efficient antithrombotic development programs not only build on traditional indications but elaborate on new therapeutic hypotheses generated from clinical studies, new therapeutic areas, and on-going basic science research programs.
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PMID:Extending the role of antithrombotic agents: an example based on the low-molecular-weight heparin, tinzaparin. 1508 61

Treatment of venous thromboembolism (VTE) has evolved significantly over the last decade. Low-molecular-weight heparins have largely replaced unfractionated heparin in the treatment of deep-vein thrombosis (DVT) but the majority of patients with pulmonary embolism (PE) continue to be treated with unfractionated heparin. Fondaparinux is the first synthetic selective inhibitor of factor Xa. It has recently been proved to be more effective than, and as safe as, a low-molecular-weight heparin for the prevention of VTE after major orthopaedic surgery. The two large randomised MATISSE trials demonstrated that fondaparinux was at least as effective and as safe as previous reference heparin therapies in the treatment of VTE. Fondaparinux should further simplify the treatment of this frequent disease since a single once-daily fixed dosage regimen may effectively and safely treat both DVT and PE, an important point especially considering the frequent though clinically silent concomitance of these two thrombotic events.
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PMID:Current perspectives on the treatment of venous thromboembolism: need for effective, safe and convenient new antithrombotic drugs. 1511 96

Anticoagulation is an essential component of the care of patients with venous thromboembolism (VTE). Traditional anticoagulants for the treatment of VTE include unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and the oral vitamin K antagonist, warfarin. A variety of anticoagulant agents with improved pharmacologic and clinical profiles are emerging and offer benefits over the traditional therapies. One of the most recent advances has been the development of new agents, such as oral direct thrombin inhibitors and factor Xa inhibitors, that have a more selective and targeted effect on the coagulation cascade. Recent clinical trials have evaluated fondaparinux, the first commercially available factor Xa inhibitor, in the treatment of patients with deep vein thrombosis and pulmonary embolism and indicate efficacy and safety as compared with traditional options such as UFH and LMWH. Fondaparinux is a welcomed addition to the available antithrombotic options.
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PMID:Evolving concepts in the treatment of venous thromboembolism: the role of factor Xa inhibitors. 1531 3

Multiple options for anticoagulation therapy are now available, placing an additional responsibility on health care workers for choosing the optimal therapy for each patient. The heparins carry a risk of heparin-induced thrombocytopenia (HIT), an immune-mediated reaction to heparin that may lead to pulmonary embolism and death. Fondaparinux, a new, synthetic pentasaccharide, binds to antithrombin III and potentiates antithrombin III's inhibition of factor Xa. Fondaparinux does not bind to platelet factor 4 and thus is theoretically unable to cause immunoallergic HIT. Unlike low-molecular-weight heparins, fondaparinux does not cross-react in vitro with sera from patients with clinical cases of HIT. These findings suggest that fondaparinux would not lead to formation of HIT antibodies and would not provoke clinical thrombosis in patients who had HIT antibodies because of previous exposure to heparins. To date, no cases of immunoallergic HIT have been associated with fondaparinux use in clinical trials. Anecdotal evidence suggests that fondaparinux eventually may prove to be valuable for preventing and treating thrombosis in patients with HIT. The effect of anticoagulants on wound healing is another consideration when choosing a thromboprophylactic strategy after major surgery. There is evidence that thrombin plays a role in wound healing, but fondaparinux is too small to enable antithrombin III to inhibit thrombin. Thus, fondaparinux may be less likely than a low-molecular-weight heparin to interfere with wound healing.
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PMID:Special considerations with fondaparinux therapy: heparin-induced thrombocytopenia and wound healing. 1531 4

Venous thromboembolism VTE remains a common but preventable disease. The last decade has witnessed major advances in VTE treatment and prophylaxis. Low molecular weight heparins LMWH became the agents of choice in the treatment of deep venous thrombosis DVT and are increasingly used in the treatment of stable pulmonary embolism PE. Increasing focus on simplicity and efficacy has led to the discovery of the synthetic pentasaccharides, substances that specifically inhibit factor Xa activity, producing an antithrombotic effect without affecting other coagulation factors or platelets. Fondaparinux, the first pentasaccharide introduced into the market, was first tried as a prophylactic agent against VTE in patients undergoing major orthopedic procedures, such as hip fracture, total hip and knee replacements, such approach appeared to be more effective than LMWH. Fondaparinux was also used, with promising results, in prophylaxis in patients undergoing major abdominal surgery and high risk medical patients. Pentasaccharides were recently tried in the treatment of both DVT and PE. The largest clinical investigation program ever undertaken in this therapeutic area, has shown that pentasaccharides are as safe and as effective as either unfractionated heparin UFH or LMWH, with the added convenience of once daily injection, no need for monitoring the anticoagulant effect and no major side effects such as thrombocytopenia. Therefore, the efficacy, the safety profile and the added convenience for both patients and physicians alike, will probably keep pentasaccharides as the front runner among new anticoagulants of the future. This article focuses on the use of fondaparinux as a prophylactic agent against VTE in patients undergoing major orthopedic and abdominal surgery along with high risk medical patients; it will also discuss the recent promising data on its use to treat active DVT and PE.
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PMID:Pentasaccharides. The new anticoagulants. 1532 84


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