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PubMedDate not supplied

[Desirudin (Revasc) to prevent thromboembolic complications after hip or knee replacement surgery].

Since March 1999, desirudin (REVASC), a recombinant hirudin, has been used in Nancy to treat patients who undergo total hip or knee replacement with a high risk of thromboembolic complications. We carried out a retrospective study using clinical data on the first 15 consecutive patients treated with desirudin to find out prescription motivations, type of shift (indirect anticoagulants or low-molecular-weight-heparin) and evolution. They all had a high risk of deep vein thrombosis (thrombophily, obesity, history of thromboembolic events). Some of this patients would have been excluded of the studies which permitted desirudin to be approved. In this study, we found no thromboembolic complications. The only striking facts are one bleeding complication (after difficult surgery) and one pulmonary embolism (2 months later).

Aged↗
PubMed2002

Acute management of atrial fibrillation: Part II. Prevention of thromboembolic complications.

Family physicians should be familiar with the acute management of atrial fibrillation and the initiation of chronic therapy for this common arrhythmia. Initial management should include hemodynamic stabilization, rate control, restoration of sinus rhythm, and initiation of antithrombotic therapy. Part II of this two-part article focuses on the prevention of thromboembolic complications using anticoagulation. Heparin is routinely administered before medical or electrical cardioversion. Warfarin is used in patients with persistent atrial fibrillation who are at higher risk for thromboembolic complications because of advanced age, history of coronary artery disease or stroke, or presence of left-sided heart failure. Aspirin is preferred in patients at low risk for thromboembolic complications and patients with a high risk for falls, a history of noncompliance, active bleeding, or poorly controlled hypertension. The recommendations provided in this article are consistent with guidelines published by the American Heart Association and the Agency for Healthcare Research and Quality.

Anticoagulants↗
PubMed2002

The -33T-->C polymorphism in intron 7 of the TFPI gene influences the risk of venous thromboembolism, independently of the factor V Leiden and prothrombin mutations.

We have previously identified, in intron 7 of the TFPI gene, a T to C single-base polymorphism (-33T-->C) which is strongly associated with total circulating TFPI antigen levels. Here we examined the influence of this polymorphism on the risk of venous thromboembolism. The polymorphism was identified in the PATHROS study population (330 cases with venous thromboembolism and 826 controls). The CC genotype was found in 6.4% of cases and 10.2% of controls (age-adjusted odds ratio 0.6; 95% CI 0.3-0.9; p = 0.03). This protective effect persisted after adjustment for oral contraception and the factor V Leiden and prothrombin gene polymorphisms. In 171 controls and 49 cases in whom blood was taken at least three months after the thrombotic event, the CC genotype was associated with significantly higher total TFPI levels than the TT genotype. These results suggest that the CC genotype of the TFPI intron 7 polymorphism is an independent protective factor for venous thromboembolism, an effect probably mediated by increased TFPI levels.

Adult↗
PubMed2002

[The oral direct thrombin inhibitor Ximelagatran Prophylaxis of venous thromboembolism in hip and knee replacement].

AIM: The efficacy and safety of the new oral, direct and selective thrombin inhibitor Ximelagatran and its active form Melagatran was analysed in patients undergoing total hip or knee replacement. METHODS AND PATIENTS: Methro II, a randomised, double-blind controlled dose-finding study, involved 1876 patients. Melagatran (1, 1.5, 2.25 or 3 mg; twice daily; start: immediately before surgery) was given subcutaneously, followed by orally administered Ximelagatran (8, 12, 18 or 24 mg, twice daily, day after surgery) and compared to subcutaneously administered dalteparin (5000 IE, once daily). Methro III was a randomised, double blind controlled study involving 2788 patients. The fixed dose of 3 mg Melagatran was given (start: 4-12 hours postoperatively) followed by oral Ximelagatran (24 mg, twice daily, day after surgery) compared to subcutaneous enoxaparin (40 mg, once daily). In both studies, dalteparin or enoxaparin was applied at the evening before operation; the treatment lasted 8 to 11 days. A bilateral venography was performed at the last day of treatment. RESULTS: In the Methro II study, 1270 patients underwent total hip, 606 total knee replacement. In both groups the thromboembolism rate was reduced depending on the dose of Ximelagatran/Melagatran. Compared to dalteparin, it was significantly lower for the Ximelagatran/Melagatran group with the highest dose. In the Methro III study 1923 patients underwent a total hip, 865 a total knee replacement. The thromboembolism rate was 31% for the Ximelagatran/Melagatran group compared to 27% for the enoxaparin group. In both studies blood loss and transfusion requirement were in the same range as with low weight molecular heparins. CONCLUSIONS: A fixed subcutaneously given dose of Melagatran, followed by orally administered Ximelagatran is effective and well tolerated as prophylaxis against venous thromboembolism.

Administration, Oral↗
PubMed2002

[Ximelagatran for treatment of venous thromboembolism].

Acute venous thromboembolism including asymptomatic and symptomatic pulmonary embolism without respiratory or cardiac failure is currently treated for 6 months, initially with subcutaneous low-molecular-weight heparin followed by oral anticoagulation. The main drawback of oral anticoagulation is caused by severe bleeding complications. Oral Ximelagatran has shown to be as effective and safe for the initial treatment of acute deep venous thrombosis compared to subcutaneous low-molecular-weight heparin followed by oral warfarin over a period of 4 weeks. Currently, oral ximelagatran is investigated versus subcutaneous low-molecular-weight heparin and oral warfarin over 6 months to demonstrate an almost equal efficacy and safety. The study is performed on a double blind and double dummy basis. Six months after oral anticoagulation of patients with acute deep venous thrombosis, recurrent venous thromboembolism may occur in up to 25% within 2 years. Ximelagatran is currently investigated versus placebo to demonstrate a reduced recurrence rate of venous thromboembolism over a period of 18 months.

Anticoagulants↗
PubMed1972

Thromboembolism and oral contraceptives. (Letter to the editor).

The article by Drill and Calhoun (219: 583, 1972) and subsequent comments (220: 416, 1972, and 221: 194, 1972) on the problem of thromboembolic episodes and oral contraceptives consider at length the problems of retrospective and prospective studies. If the critical standards presented had been applied to the articles cited by Drill and Calhoun, there would not have been much left to discuss. The citations of Goldzieher and of Tyler, for example, are not to research reports but to short sections of articles of a very general nature. Tyler's comments are not even quantitative. 10 of the 15 articles cited by Drill and Calhoun in their principle tabulation (Table 3) were readily available to me. When I arranged these articles in order of scientific merit as regards the embolism problem, it became apparent that the better the quality of the scientific effort, the higher was the reported incidence of thromboembolism and the lower the number of subjects. It is very possible that the inclusion of a few casual reports with large numbers of subjects is producing an erroneous, low, overall incidence of thromboembolic episodes.

Biology↗
PubMed2002

"It's good to talk"--an audit of the communication of post-operative thromboembolic complications.

The risk of venous thromboembolism after surgery, with its associated morbidity and mortality, is an important component of obtaining informed consent for a surgical procedure. This risk of thromboembolic complications extends beyond the post-operative hospital stay; patients suffering such complications after discharge are generally not re-admitted under the care of the operating surgeon. A retrospective opening loop audit was undertaken to investigate the communication of post-operative thromboembolic complications between specialties in a large district general hospital. The operating surgeon was unaware of 87% of cases of pulmonary embolism and 20% of cases of deep vein thrombosis affecting patients in their post-operative period. The inter-specialty communication of post-operative complications is important to maintain a high standard of patient care and allow surgeons to make informed decisions about clinical practice.

Communication↗
PubMed2003

Prevention of thromboembolism in patients with mitral stenosis and associated atrial fibrillation: effectiveness of low intensity (INR target 2) oral anticoagulant treatment.

Mitral stenosis (MS) in association with atrial fibrillation (AF) is a clinical condition at high risk for systemic thromboembolism. Although oral anticoagulants greatly reduce the incidence of thromboembolism in these patients, the optimal intensity of treatment has never been tested in specific clinical trials, and current recommendations are derived from studies of nonrheumatic AF. In this study we tested the effectiveness of two different intensities. The study design was carried out as an open randomized prospective study in an anticoagulation clinic. We randomized 103 patients with MS and AF to a low (target INR = 2) or moderate (target INR = 3) anticoagulation regimen. The primary end points were systemic thromboembolism, major bleeding and vascular death. During a mean follow-up of 4.5 years, 1 systemic embolism occurred in the low intensity group (0.41 per 100 pt/yrs, CI 0.01-2.3), and 1 minor stroke occurred in the moderate intensity group (0.40 per 100 pt/yrs, CI 0.01-2.3; p = ns). Major bleeding occurred in 8 patients, with 3 in the low intensity (1.25 per 100 pt/yrs) and 5 in the moderate intensity group (2.0 per 100 pt/yrs, Incidence Rate Ratio 0.6, CI 0.1-3.1; p = ns). Total events (systemic embolism, major bleeding and vascular death) occurred in 7 low intensity patients and 8 moderate intensity patients. As expected, minor bleeding was more frequent in the moderate intensity group of patients, who actually had more intense treatment and required closer monitoring of oral anticoagulant treatment. These data suggest that low intensity anticoagulation, as performed in an anticoagulation clinic, is effective and safe in high risk patients with MS and AF.

Acenocoumarol↗
PubMed2002

[Antiphospholipid antibodies as risk factor for venous thromboembolism].

The aim of the following study was to determine the prevalence of lupus anticoagulant (LA) and anticardiolipin antibodies (ACL) in patients with a history of venous thromboembolism (VTE). The patient group comprised 218 subjects with VTE before the age of 45, recurrent VTE or thrombosis in an unusual site. The control group consisted of 218 age, and sex-matched healthy individuals. LA and/or ACL were detected in 19 among 218 patients (8.7%). Lupus anticoagulant was found in 17 patients with VTE and in none out of 218 controls. The odds ratio for having venous thromboembolism was 14.1 (95% CI: 1.8-108.8) for patients with LA. Lupus anticoagulant is significantly associated with VTE. The prevalence of anticardiolipin was similar in patients and in controls. The results of our study indicate that anticardiolipin antibodies are not associated with venous thromboembolism.

Adolescent↗
PubMed2003

[Combined diagnostic approach to venous thromboembolism with multidetector computed tomography].

BACKGROUND: Multidetector computed tomography (CT) improves scan length and spatial resolution. The availability of a single test that allows a comprehensive evaluation of the chest and pulmonary arteries, of the deep venous system of the abdomen and legs and the hemodynamic impact of pulmonary emboli on the right heart could be a new and effective strategy for patients with venous thromboembolic disease. We assess a combined study protocol on venous thromboembolic disease by multidetector CT. METHODS: Twenty-four patients with confirmed acute pulmonary embolism, in stable clinical conditions, underwent multidetector CT. After antecubital intravenous infusion of 120 ml of contrast medium at a rate of 4 ml/s followed by 30 ml of saline solution a CT of the chest was performed using 4 x 1 mm collimation, pitch 1.5 and 500 ms rotation time of the X-ray tube; the start delay was checked for each single patient. Indirect CT venography study was acquired 150s after starting the infusion using a 5 mm section width from the diaphragm to the popliteal zone. We evaluated: 1) the presence of intraluminal filling defects in the pulmonary arteries and in the deep venous system from the inferior vena cava to the popliteal veins, and 2) the presence of right ventricular dilation with a right ventricle/left ventricle (RV/LV) ratio > 1. The patients with CT diagnosis of deep vein thrombosis (DVT) and and RV/LV ratio > 1 underwent venous compressive ultrasound and/or echocardiography. RESULTS: Pulmonary embolism was detected in 12% in the main arteries and in 66, 87 and 20% in the lobar, segmental and subsegmental arteries respectively. DVT was found in 14/24 (58%) patients with pulmonary embolism involving the ileo-femoral district in 14% of the whole group. Thirteen patients (54%) showed a volumetric prevalence of the right ventricle on the left ventricle. CT data in the presence of DVT and an RV/LV ratio > 1 was confirmed at ultrasonography. CONCLUSIONS: Multidetector CT allows to obtain rapidly and in one examination useful information about the source and pulmonary involvement of venous thromboembolic disease and about the hemodynamic impact on the right heart.

Aged↗
PubMed1992

Treatment of venous thromboembolism in patients with congenital deficiency of antithrombin III.

The treatment course of all thromboembolic events in the patients with congenital deficiency of antithrombin III (AT III) in the national Swedish register was reviewed in order to assess the appropriate medical therapy in this situation. The medical treatment of 70 events of venous thromboembolism was evaluated. There were eight cases with signs of clinical progression. The risk of therapeutic failure with heparin could be as low as 1.5% or as high as 9.2%. It would not be cost-effective to substitute with concentrates of AT III in every case with congenital deficiency thereof in connection with acute venous thromboembolism. "Heparin resistance" does not seem to be a problem in the vast majority of these patients.

Adult↗
PubMed1992

[Acetylsalicylic acid in unstable angina, after coronary revascularization and in prevention of cardiac thromboembolism].

Acetylsalicylic acid (ASA) inhibits platelet function via cyclooxygenase inhibition. The selective inhibition of platelet cyclooxygenase is possible with the use of low doses of ASA due to presystemic acetylation of the platelet enzyme in the portal circulation. The clinical efficacy of ASA has been demonstrated for a number of indications. ASA reduces the rate of myocardial infarctions and cardiovascular deaths in patients with unstable angina. Simultaneous intravenous infusion of heparin has an additional positive effect. The prevention of acute coronary thromboses during PTCA and of early bypass graft occlusion has been convincingly demonstrated, if therapy is initiated immediately after surgery. Neither ASA nor any other drug has been effective in the prevention of late restenosis following PTCA and of late bypass graft occlusions. Thromboembolic complication after implantation of biological valve prostheses is significantly reduced by ASA, if no rheumatic valve disease is present. The rate of peripheral or cerebral thromboembolic events is markedly increased in patients with lone atrial fibrillation. In contrast to the very positive results obtained for anticoagulants, the reports with ASA were contradictory. ASA may be effective in preventing thromboembolic complications in younger patients with a lower risk or in elderly patients with contraindications for anticoagulation. For most clinical indications the efficacy of ASA has been demonstrated for doses of 75-324 mg/d. Following a loading dose of 300 mg on the first day, continuation of therapy with 100 mg/d should combine maximal therapeutic efficacy with a low rate of unwanted drug effects.

Angina, Unstable↗
PubMed2003

[Conclusions of consensus development conferences on the prevention and treatment of venous thromboembolism].

An education program for hospital physicians and family doctors including up to date knowledge on diagnosis, prevention and treatment of venous thromboembolism has been elaborated, chiefly within the framework of hospital consensus conferences. Postgraduate consensus meetings led by representatives of specialities interested in prophylaxis of venous thrombosis have been held in 64 hospitals all over the country during the years 1996 to 2002, with a total number of more than 10,000 doctors working in hospital or general practice. In contrast to descriptive reports offered so far on drugs, the aim was a comprehensive clinical review of the problem, according to the principle of "disease management". By this way not only new diagnostic, therapeutic and prophylactic methods were presented but we managed to shape a new attitude based on new pathophysiological findings. As a result of the conferences the incidence and mortality of venous thromboembolism has decreased both on hospital and national levels. The consensus meetings acting as local interdisciplinary postgraduate forums have been supported by the Hungarian Thrombosis and Haemostasis Society and the haemostasis workshops of the country (Budapest, Debrecen, Pécs, Szombathely). Shaping the principles and methods for prophylaxis and therapy of venous thromboembolism can be regarded as a model which can subsequently be adapted to the problems of arterial thrombosis as well.

Consensus Statements as Topic↗
PubMed2003

[Thromboembolic complications in laparoscopic surgery and their prophylaxis].

Frequency of thromboembolic complications occurrence after laparoscopic intervention was studied in 8230 patients. Efficacy of prophylactic perioperative application of low-molecular heparin fraxiparin was estimated. Thrombosis of deep veins had occurred in 6 (0.073%), thromboembolism of pulmonary artery--in 3 (0.037%) patients. General frequency of thromboembolic complications had constituted 0.11%.

Adolescent↗
PubMedDate not supplied

[Cost-effectiveness analysis of enoxaparin for the prophylaxis of venous thromboembolism in major orthopedic surgery patients].

OBJECTIVES AND METHODS: A retrospective, modeled, cost-effectiveness analysis was conducted with enoxaparin versus non-prophylaxis, tinzaparin, and unfractionated heparin for venous thromboembolic disease in Spanish patients undergoing major orthopedic surgery from the standpoint of the Spanish national health system. Episodes avoided and life-years gained with each treatment were estimated by a meta-analysis of clinical trials. RESULTS: With enoxaparin fewer thromboembolic episodes and deaths occurred, when compared to the available alternative options. Enoxaparin was the dominant option (lower total cost and equal or greater effectiveness than any alternative option) in comparison with non-prophylaxis, tinzaparin, and unfractionated heparin. A sensitivity analysis confirmed the stability of these results. CONCLUSION: The administration of enoxaparin as a prophylactic treatment for venous thromboembolic disease in patients undergoing hip or knee surgery is a cost-effective intervention in every case, and less expensive than the alternative options used in Spain.

Cost-Benefit Analysis↗
PubMed2003

[Prevention of postoperative venous thromboembolism in patient with brain tumor].

The surgical treatment results in 610 patients with brain tumors and thromboembolic complications were analyzed. Deep venous thrombosis was registered in 8 (1.3%) patients; 0.65% of patients died from pulmonary thromboembolism. We used complex prevention measures including low molecular weight heparin (LMWH) fraxiparine to prevent thromboembolic complications after operation. LMWH may be considered as a part of treatment standards in patients with brain tumors.

Brain Neoplasms↗
PubMed2004

Thromboembolic events occur despite sinus rhythm maintenance in patients treated for atrial fibrillation: The Canadian Trial of Atrial Fibrillation experience.

BACKGROUND: Anticoagulation reduces the risk of stroke in patients with atrial fibrillation. It is not clear whether patients who revert and are maintained in sinus rhythm should continue to receive warfarin. The recommendation is to anticoagulate these patients for a minimum of four weeks after cardioversion. Whether warfarin should be maintained for a longer period of time is unknown. METHODS AND RESULTS: To address this question, data from the Canadian Trial of Atrial Fibrillation were reviewed. Among the 403 patients, 81.9% had at least one risk factor for stroke, of whom only 60% were on warfarin. Nine thromboembolic events occurred in nine patients (2.2%): all had at least one risk factor for stroke. Six events occurred in patients who were either not anticoagulated (n=4) or for whom the international normalization ratio was subtherapeutic (n=2). Eight of the nine patients were in sinus rhythm at the last follow-up visit before and at the time of evaluation of the thromboembolic event. CONCLUSIONS: Anticoagulants are underused in atrial fibrillation patients at risk of stroke. Thromboembolic events are most often associated with suboptimal levels of anticoagulation and they occur despite the appearance of sinus rhythm maintenance.

Aged↗
PubMed2004

New anticoagulants and their potential impact on the treatment of thromboembolic disease.

Traditional anticoagulants have drawbacks that make them complex to manage, limit their usefulness, and increase the possibility of adverse events. New anticoagulants are being developed that directly target a single coagulation factor. The agents have improved pharmacokinetics and pharmacodynamics and may not need coagulation monitoring. In addition, many are available orally. Agents that target factor Xa or factor IIa are the most advanced in development and of greatest interest. Fondaparinux and idraparinux are parenteral, specific, indirect, factor Xa inhibitors that have a mechanism of action similar to that of heparin. Idraparinux has a prolonged half-life and is dosed once weekly. Razaxaban is a small-molecule, oral, direct FXa inhibitor with demonstrated efficacy in orthopedic surgery for primary prevention of venous thromboembolism. Other oral Xa inhibitors are entering clinical trials. Ximelagatran is an oral factor IIa or thrombin inhibitor with documented efficacy for primary prevention of venous thromboembolism in orthopedic surgery, for the acute and chronic treatment of deep venous thrombosis and stroke prevention in atrial fibrillation. Other oral IIa inhibitors are entering clinical trials. Many of these agents will have a profound effect on the treatment of venous thromboembolism potentially resulting in reduced costs, improved patient satisfaction with treatment, and greater use of selected indications.

Anticoagulants↗