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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Management of venous thromboembolism disease could be improved by new drugs with lower risk of bleeding and without the need of regular monitoring of anticoagulant effect. In this way, idraparinux, anti-Xa inhibitor, has been compared to conventional therapy (coumarins) for the treatment of deep vein thrombosis and pulmonary embolism. Is it worth to treat patients more than six months? This has been evaluated in an interesting study. Prophylaxis after hip replacement surgery is indicated to reduce the risk of venous thromboembolism, new drugs are under investigation. Dabigatran etexilate, a direct thrombin inhibitor, has been shown as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery. In 2007, new european guidelines for non-STsegment elevation acute coronary syndromes have been published. Two new antithrombotic drugs, bivalirudin and fondaparinux, are now part of the different possible choices according to specific considerations. New factor Xa and factor IIa inhibitors are under investigation and are compared to heparin in PCI for NSTE-ACS. Fondaparinux and more recently otamixaban have given interesting results. These new recommendations have not yet taken into account new data published in 2007. What will be the positioning of prasugrel, a new thienopyridine, after the results of theTRITON trial? In patients with SCA treated by PCI, prasugrel reduced the ischemic events, while increasing major bleedings. In 2007, numerous publications and meta-analyses on drug-eluting stents (DES) have been published and tempered the fear about a possible increase in mortality with the use of DES.
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PMID:[What's new on antithrombotics?]. 1895 Jul 43

An 11-year-old female developed heparin induced thrombocytopenia (HIT) with thrombosis during therapy for lower extremity deep vein thrombosis and pulmonary embolism. Transition from bivalirudin, a direct thrombin inhibitor (DTI), to warfarin resulted in extensive re-thrombosis, and fondaparinux therapy similarly failed. She was then treated with argatroban, and transitioned successfully to warfarin after 9 weeks. The risk of re-thrombosis was ultimately reduced by allowing time for the thrombogenic potential to abate. The argatroban/warfarin transition was monitored with chromogenic factor X levels. This case highlights several difficult problems in pediatric thrombosis.
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PMID:Heparin induced thrombocytopenia and re-thrombosis associated with warfarin and fondaparinux in a child. 1941 34

(1) The standard anticoagulant for preventing thromboembolic events after hip or knee replacement surgery is a subcutaneous low-molecular-weight heparin such as enoxaparin; (2) Dabigatran, a specific thrombin inhibitor, was recently licensed for oral prophylaxis in this setting, as dabigatran etexilate (mesilate), a prodrug; (3) The clinical evaluation of dabigatran in this indication is based on two comparative double-blind trials with similar protocols, comparing dabigatran 150 mg or 220 mg/day versus enoxaparin in 3494 patients undergoing hip replacement surgery and 2101 patients undergoing knee replacement surgery. The results were virtually identical: compared with enoxaparin, dabigatran did not reduce overall mortality (almost zero in the different groups), the frequency of symptomatic pulmonary embolism (almost zero in the different groups), or the frequency of symptomatic deep venous thrombosis (0.1% to 1.2%); (4) There was no difference between the groups with respect to the frequency of severe bleeding (about 1.5%), hepatic disorders (about 4%), or acute coronary events (a few cases). But dabigatran was associated with surgical wound seepage in 7% of patients, versus 4.7% with enoxaparin; (5) The anticoagulant effect of dabigatran, and therefore the frequency of haemorrhage, increases with age and in cases of renal failure. However, clinical trials included relatively few elderly patients and/or patients with renal failure, who nonetheless represent a large proportion of the candidates for hip or knee replacement; (6) Dabigatran becomes more potent when combined with P-glycoprotein inhibitors or with drugs that impair renal function. Combination with other antithrombotic drugs should be avoided. (7) Dabigatran is administered orally, while enoxaparin requires daily subcutaneous injections. Dabigatran therapy does not necessitate laboratory monitoring, while the platelet count must be monitored with enoxaparin. There is no known antidote for dabigatran overdose; (8) In summary, for the prevention of venous thromboembolic events after orthopaedic surgery, it is better to continue to use heparins, at least pending more thorough evaluation of dabigatran.
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PMID:Dabigatran: new drug. Continue to use heparin, a better-known option. 1963 11

The direct thrombin inhibitor lepirudin is mainly applied in heparin-induced thrombocytopenia. We report here the case of a 37-year-old kurdish woman in whom Behcets disease was diagnosed in 1998 when she presented with a Budd Chiari syndrome (BCS) complicated by pulmonary embolism. Recurrent venous thromboembolism (VTE) occurred despite anticoagulant therapy with UFH, LMWH or phenprocoumon and various immunosuppressive therapy regimens. In 2001, when BCS recurred ultimately i.v. lepirudin was administered. When the patient improved and remained clinically stable lepirudin was applied subcutaneously. During long-term treatment with twice-daily 50 mg no further VTE was observed over the following years. Additionally, no bleeding complications occurred. In May 2005 anticoagulant therapy was switched to phenprocoumon. BCS reoccurred when INR values were suboptimal in February 2007, and lepirudin treatment was immediately restarted. After admission the patient received 50 mg b.i.d. lepirudin s.c. with plasma levels in the therapeutic range (0.5-1.0 mg / l). Over the following months, lepirudin levels repeatedly exceeded the upper limit of this range and the dosage was stepwise reduced. Finally, 20 mg b.i.d. were sufficient to obtain therapeutic levels. Renal function was normal, but lepirudin antibodies were present in high titer, as assessed by ELISA. We suppose that these antibodies reduce renal filtration of lepirudin thus leading to increased plasma levels. This case is an example for successful long-term therapeutic-dose anticoagulation with s.c. lepirudin in a patient with Behcets disease and recurrent VTE despite therapeutic anticoagulant therapy with LMWH or vitamin K antagonists. However, frequent measurement of lepirudin plasma levels is needed. If stepwise dose lowering is required over time, the presence of lepirudin antibodies should be considered.
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PMID:Alteration of pharmacokinetics of lepirudin caused by anti-lepirudin antibodies occurring after long-term subcutaneous treatment in a patient with recurrent VTE due to Behcets disease. 2018 83

This trial compared the efficacy and safety of oral dabigatran, a direct thrombin inhibitor, versus subcutaneous enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty. A total of 2,055 patients were randomised to 28-35 days treatment with oral dabigatran, 220 mg once-daily, starting with a half-dose 1-4 hours after surgery, or subcutaneous enoxaparin 40 mg once-daily, starting the evening before surgery. The primary efficacy outcome was a composite of total venous thromboembolism [VTE] (venographic or symptomatic) and death from all-causes. The main secondary composite outcome was major VTE (proximal deep-vein thrombosis or non-fatal pulmonary embolism) plus VTE-related death. The main safety outcome was major bleeding. In total, 2,013 were treated, of whom 1,577 operated patients were included in the primary efficacy analysis. The primary efficacy outcome occurred in 7.7% of the dabigatran group versus 8.8% of the enoxaparin group, risk difference (RD) -1.1% (95%CI -3.8 to 1.6%); p<0.0001 for the pre-specified non-inferiority margin. Major VTE plus VTE-related death occurred in 2.2% of the dabigatran group versus 4.2% of the enoxaparin group, RD -1.9% (-3.6% to -0.2%); p=0.03. Major bleeding occurred in 1.4% of the dabigatran group and 0.9% of the enoxaparin group (p=0.40). The incidence of adverse events, including liver enzyme elevations and cardiac events, during treatment was similar between the groups. Extended prophylaxis with oral dabigatran 220 mg once-daily was as effective as subcutaneous enoxaparin 40 mg once-daily in reducing the risk of VTE after total hip arthroplasty, and superior to enoxaparin for reducing the risk of major VTE. The risk of bleeding and safety profiles were similar.
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PMID:Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, double-blind, non-inferiority trial. 2135 12

The incidence of venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is increasing and the disease has been found to account for over 500,000 annual deaths in the European Union. VTE is associated with increased mortality and may lead to serious long-term complications. Unfractionated heparin (UFH), low molecular weight heparin (LMWH) and vitamin K antagonists (VKA) have remained standard of care for many years. Recent trials of novel anticoagulants have indicated that new therapeutical options may soon become available. Studies on the role of new agents in VTE prevention in patients undergoing orthopaedic surgery have provided the evidence suggesting potential value of these drugs for the management of acute events. At present, investigation of new anticoagulants has reached the stage when phase III clinical studies on some novel agents have been completed and others are in progress. Of those furthest along are the direct Factor Xa inhibitors, rivaroxaban and apixaban, and the direct thrombin inhibitor, dabigatran. Findings of ongoing trials are expected to determine potential impact of these agents on current clinical practice.
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PMID:Emerging options in the treatment of deep vein thrombosis and pulmonary embolism. 2160 28

Following the landmark study by Barritt and Jordan in 1960, in which patients with venous thromboembolism (VTE) were randomized to no treatment or a combination of heparin and warfarin, antithrombotic therapy for this disease became widely accepted. This study was stopped prematurely because half of the non-treated patients had recurrent pulmonary embolism (PE), or died. It was subsequently found that after a VTE, patients given warfarin alone had a 3-4-fold higher incidence of recurrent VTE than patients given both heparin and warfarin. Since the 1990 s, standard therapy for VTE has comprised an initial 5-7 day course of parenteral anticoagulant plus warfarin continued for at least 3 months. Recently, several orally active small molecules have been evaluated in the treatment of VTE, including a direct thrombin inhibitor and direct Factor Xa inhibitors. Other novel oral agents are also in development for VTE treatment. Although the DTI ximelagatran, the first oral agent to be introduced since warfarin was withdrawn from the market in Europe because of hepatotoxicity, evidence from clinical trial evaluating other single target-specific oral agents in the treatment of VTE is encouraging. It is therefore likely that use of warfarin in the treatment and secondary prevention of VTE will decrease should these novel oral agents be introduced for these indications. Additionally, there will be less distinction between initial and long-term therapy, and a great majority of patients will be treated on an outpatient basis for prolonged periods of time. Recently these expectations were fulfilled by the results of two Phase III studies in patients with VTE. The Recover I study indicated that Dabigatran (150 mg b.d.) following an initial course of LMWH was non-inferior to the standard treatment of LMWH plus warfarin, with also a similar safety profile. The Einstein DVT study revealed that Rivaroxaban as a single agent can safely replace the standard treatment in patients with DVT. Taken together these studies and a few others that have or are about to be completed will indeed introduce a paradigm shift in the way patients with VTE will be treated.
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PMID:[New treatments for venous thromboembolic disease]. 2217 64

Venous thromboembolism, presenting as deep vein thrombosis or pulmonary embolism, is a major challenge for health care systems. It is the third most common vascular disease after coronary heart disease and stroke, and many hospitalized patients have at least one risk factor. In particular, patients undergoing hip or knee replacement are at risk, with an incidence of asymptomatic deep vein thrombosis of 40%-60% without thromboprophylaxis. Venous thromboembolism is associated with significant mortality and morbidity, with patients being at risk of recurrence, post-thrombotic syndrome, and chronic thromboembolic pulmonary hypertension. Arterial thromboembolism is even more frequent, and atrial fibrillation, the most common embolic source (cardiac arrhythmia), is associated with a five-fold increase in the risk of stroke. Strokes due to atrial fibrillation tend to be more severe and disabling and are more often fatal than strokes due to other causes. Currently, recommended management of both venous and arterial thromboembolism involves the use of anticoagulants such as coumarin and heparin derivatives. These agents are effective, although have characteristics that prevent them from providing optimal anticoagulation and convenience. Hence, new improved oral anticoagulants are being investigated. Dabigatran is a reversible, direct thrombin inhibitor, which is administered as dabigatran etexilate, the oral prodrug. Because it is the first new oral anticoagulant that has been licensed in many countries worldwide for thromboprophylaxis following orthopedic surgery and for stroke prevention in patients with atrial fibrillation, this compound will be the main focus of this review. Dabigatran has been investigated for the treatment of established venous thromboembolism and prevention of recurrence in patients undergoing hip or knee replacement, as well as for stroke prevention in atrial fibrillation patients with a moderate and high risk of stroke.
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PMID:New oral antithrombotics: focus on dabigatran, an oral, reversible direct thrombin inhibitor for the prevention and treatment of venous and arterial thromboembolic disorders. 2232 96

The quest for novel medications to treat thromboembolic disorders such as venous thrombosis, pulmonary embolism and stroke received a boost when the 3D structures of two major players in the blood coagulation cascade were determined in 1989 and 1993. Structure-guided design of inhibitors of thrombin (factor IIa, fIIa) and factor Xa (fXa) eventually led to the discovery of potent, selective, efficacious, orally active and safe compounds that proved successful in clinical studies. In 2008, the direct thrombin inhibitor dabigatran etexilate developed by Boehringer Ingelheim became the first novel antithrombotic molecular entity to enter the market in 50 years. Additional compounds targeting factor Xa were subsequently granted marketing authorization or are in late-stage clinical studies. In this review, I use selected case studies to describe the discovery of novel fIIa and fXa inhibitors, with a particular emphasis on the pre-eminent role that structural information played in this process.
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PMID:The role of structural information in the discovery of direct thrombin and factor Xa inhibitors. 2250 39

Total hip arthroplasty is a frequently performed orthopedic surgical procedure, and the number of these surgeries is expected to increase significantly over the coming years. Patients undergoing joint arthroplasty are at a particularly high risk for developing venous thromboembolic events (eg, deep vein thrombosis and pulmonary embolism). Prevention of postoperative complications is an important responsibility not only for orthopedic surgeons, but also for other clinicians involved in patients' care. Effective thromboprophylaxis is crucial to reduce the risk of developing venous thromboembolism following total hip arthroplasty and is an important goal of therapy. In response to some of the practical limitations of traditional anticoagulants, a new generation of oral anticoagulants has been developed. These agents include the selective factor Xa inhibitors, rivaroxaban and apixaban, and the direct thrombin inhibitor dabigatran etexilate. The objective of this review article is to update hospitalists on the trial data and clinical considerations surrounding the new anticoagulants. Hospitalists play a key role in caring for surgical patients either in a consultative role or in conjunction with surgical teams. Thus, a practical knowledge of recent developments in thromboprophylaxis is essential for providing high-quality, evidence-based care.
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PMID:Preventing venous thromboembolic events after total hip arthroplasty: new developments in clinical practice. 2261 82


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