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PubMed2002

Hyperhomocysteinemia and venous thromboembolism: a risk factor more prevalent in the elderly and in idiopathic cases.

Fasting plasma homocysteine level and the related clinical findings were analysed in 240 consecutive patients with venous thromboembolism. Hyperhomocysteinemia, defined as a plasma level above 20 micromol/l (corresponding to the percentile 95th in the controls), was present in 11.2% of the patients. Plasma homocysteine level was similar in patients presenting with either deep venous thrombosis, pulmonary embolism or both conditions. It was significantly higher in patients with primary (unprovoked) VTE than in patients with secondary disease (associated with at least one risk factor): 12.3 vs. 9.55 micromol/l (p < 0.005). Mean homocysteine was higher in male than in female patients (14.51 vs. 12.9 micromol/l, p < 0.05) and increased significantly with age. Hyperhomocysteinemia was more frequent in patients with relapsing disease (14 of 76, 18.4%) than in those presenting with a single episode (13 of 164, 7.9%) (p = 0.034). Furthermore, hyperhomocysteinemia was correlated with reduced protein C level (p = 0.013). In a multivariate analysis, two factors were significantly associated with hyperhomocysteinemia: older age (p < 0.0001) and idiopathic occurrence (p < 0.02). Since the frequency of homozygous MTHFR thermolabile variant was rather similar in patients and controls, testing for C677T mutation was not helpful in screening VTE patients. However, the homozygous mutation was significantly more prevalent among hyperhomocysteinemia patients, confirming its role in the genesis of hyperhomocysteinemia. According to its prevalence, to the putative role in venous and arterial disease and the availability of an effective and low-cost corrective therapy, hyperhomocysteinemia deserves interest, especially in the elderly and in the patients with idiopathic VTE disease.

Adolescent↗
PubMed2003

Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement.

BACKGROUND: In a previous study of the prevention of venous thromboembolism after total knee replacement, the efficacy of ximelagatran, an oral direct thrombin inhibitor that does not require monitoring of coagulation or dose adjustment, was found to be similar to that of warfarin at a dose of 24 mg of ximelagatran twice daily. The purpose of the present study was to determine whether a higher dose of ximelagatran is superior to warfarin. METHODS: This randomized, double-blind trial compared a regimen of 7 to 12 days of oral ximelagatran, at a dose of 24 or 36 mg twice daily, starting the morning after surgery, with warfarin therapy started the evening of the day of surgery. The composite end point of venous thromboembolism and death from all causes and the incidence of bleeding were the primary outcome measures. RESULTS: Among the 1851 patients in the efficacy analysis, oral ximelagatran at a dose of 36 mg twice daily was superior to warfarin with respect to the primary composite end point of venous thromboembolism and death from all causes (20.3 percent vs. 27.6 percent; P=0.003). There were no significant differences between these two groups with respect to major bleeding (incidence, 0.8 percent and 0.7 percent, respectively), perioperative indicators of bleeding, wound characteristics, or the composite secondary end point of proximal deep-vein thrombosis, pulmonary embolism, and death (2.7 percent vs. 4.1 percent; P=0.17). CONCLUSIONS: The efficacy of oral ximelagatran, administered starting the morning after total knee replacement, was superior to that of warfarin for prevention of venous thromboembolism. Rates of hemorrhagic complications with the two drugs were similar.

Administration, Oral↗
PubMed1982

Thrombolytic therapy. For pulmonary embolism and deep venous thrombosis.

Thrombolytic agents are effective in acute pulmonary embolism and thrombosis in the popliteal and proximal deep veins. Patients with recent thromboemboli, as manifested by onset of symptoms within the previous five days, respond best. Bleeding complications can be greatly reduced by proper patient selection and by avoidance of invasive procedures. Thrombolytic agents are easily administered, and laboratory monitoring has been simplified. Anticoagulants must be given when thrombolytic therapy is completed, since the thrombotic tendency probably still exists.

Blood Coagulation Tests↗
PubMed2004

Prevention of venous thromboembolism in the plastic surgery patient.

The term venous thromboembolism refers to a spectrum of disease that includes deep venous thrombosis and pulmonary embolism. Both deep venous thrombosis and pulmonary embolism are often clinically silent and thus difficult to diagnose, which leads to a substantial delay in treatment that results in high rates of morbidity and mortality. The purposes of this article are to help physicians determine the proper venous thromboembolism prophylaxis and to simplify the complex problem of treating venous thromboembolism. The tools provided in this article will help expedite and clarify the decision-making process.

Adult↗
PubMed2006

Pulmonary embolism and deep jugular venous thrombosis resulting from compression by a lipoma.

Lipomas usually extend in subcutaneous tissues and rarely may be compressive. We report a case of neck lipoma resulting in jugular vein thrombosis and pulmonary embolism in a patient treated by clozapine. Clozpine may be considered an associated risk factor for thrombosis. This case suggests that performing a regional evaluation may be particularly important when thrombophlebitis occurs.

Antipsychotic Agents↗
PubMed2001

[Clinical practice guidelines of the Spanish Society of Cardiology for pulmonary thromboembolism and hypertension].

Primary pulmonary hypertension is a progressive disease. Most affected patients are young and middle-aged women. Etiology is unknown, although a familial and genetic factor is present in up to 6% of cases. Endothelial dysfunction and abnormalities in calcium channels of smooth muscle fibers are the present pathogenetics theories. Diagnostic tests try to exclude secondary causes of pulmonary hypertension and to evaluate its severity. Acute vasodilatory test is vital in the selection of treatment. Oral anticoagulation is indicated in all patients. Lung transplant is performed when medical treatment is unsuccessful. Atrial septostomy is an alternative and palliative treatment for selected cases. Chronic thromboembolic pulmonary hypertension is a special form of secondary pulmonary hypertension, clinically undistinguishable from primary primary hypertension, is of mandatory diagnosis because it can be cured with thromboembolectomy. Pulmonary embolism is common in hospitalised patients. The mortality rate for pulmonary embolism continues to be high: up to 30% in untreated patients. The accurate detection of pulmonary embolism remains difficult, as pulmonary embolism can accompany as well as mimic other cardiopulmonary illnesses. Non-invasive diagnostic tests have poor specificity and sensitivity. The D-dimer level and the spiral CT angiography have also been employed as new alternatives and important tools for precise diagnosis of suspected pulmonary embolism. The standard therapy of pulmonary embolism is intravenous heparin for 5 to 10 days in conjunction with oral anticoagulants posteriorly for 3 to 6 months. The incidence of deep venous thrombosis, pulmonary embolism and death due to pulmonary embolism, can be reduced significantly and shown clear benefits only by adoption of a prophylactic strategy with low-molecular-weight-heparins or dextrans in patients at risk.

Algorithms↗
PubMed1989

[Lung embolism during and following long-distance flights ("economy class syndrome")].

Two cases of venous thrombosis and pulmonary embolism during or after intercontinental air travel occurring in two sisters with venous thromboembolic risk factors are presented. In one the outcome was fatal. In the present era of mass tourism the probably underestimated risk of thromboembolism in air travel should be kept in mind. As prophylactic measures leg exercises, walking and high fluid intake during the flight are recommended. Sleeping in the sitting position should be avoided. For persons at high risk, prophylactic anticoagulation may be considered.

Adult↗
PubMed1991

[Heparin in the treatment and secondary prevention of myocardial infarction. A critical review of the main trials].

The aim of this article is to assess the therapeutic value of standard heparin in the acute phase and secondary prevention of myocardial infarction. Only clinical trials with an adequate methodology have been analysed. In patients having undergone thrombolytic therapy associated with aspirin, heparin slightly reduces the mortality but only during the period of its administration. In a metaanalysis of approximately twenty clinical trials of patients not receiving thrombolytic or aspirin therapy, heparin was associated with a significant reduction of deep vein thrombosis, pulmonary embolism, recurrent myocardial infarction and cerebrovascular accidents. In the context of secondary prevention of myocardial infarction, the administration of a moderate dose of subcutaneous heparin resulted in a beneficial effect on morbidity and mortality in one published trial. The use of low molecular weight heparins for the prevention of coronary thrombosis merits attention because of the pharmacological and pharmacokinetic properties of these products.

Cerebrovascular Disorders↗
PubMed2004

Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. A cost-utility analysis.

BACKGROUND: Among patients undergoing elective total hip or knee replacement, prolonged prophylaxis with low-molecular-weight heparin significantly reduces the risk of symptomatic venous thromboembolism. Whether implementing routine prolonged prophylaxis is cost-effective remains uncertain. METHODS: We performed an economic modeling study to compare the costs and health outcomes of standard (12 days) with prolonged (42 days) enoxaparin prophylaxis against venous thromboembolism after elective total hip and knee replacement. The primary economic perspective was that of a societal healthcare payer, taking Belgium as a case country. We used cost-utility analysis, a form of cost effectiveness analysis in which costs are reported in monetary terms (euros) and health outcomes are converted into quality-adjusted life years (QALYs) gained, thereby incorporating a measure of quality of life (utility) into the health outcomes. Costs for diagnosis and treatment of proximal and distal deep vein thrombosis, pulmonary embolism, postphlebitic syndrome, and major bleeding were obtained from a Delphi panel (orthopaedic surgeons) and the official reimbursement rates (Federal Ministry of Health). QALYs for these health outcomes were based on utility scores as reported in the literature. The main outcome measure was the incremental cost-utility ratio, reported as the incremental cost per quality-adjusted life year gained (euros/QALY). The incremental cost-utility ratio refers to the amount of money needed to produce one additional QALY. We also performed sensitivity analyses on clinical and economic parameters to identify important model uncertainties. RESULTS: In the base-case analysis, incremental costs of prolonged prophylaxis amounted to 58 euros and 114 euros per patient, with an additional gain in QALY of 0.0083 and 0.0018 after total hip and knee replacement, respectively. Thus, a strategy of prolonged enoxaparin prophylaxis was associated with a cost-utility ratio of 6,964 euros/QALY and 64,907 euros/QALY after total hip and knee replacement, respectively. This tenfold difference in incremental cost-utility ratios between hip and knee replacement might have important practical implications. According to recent European guidelines, an intervention costing less than 20,000 euros per QALY is said to exhibit strong evidence for adoption, whereas one costing 20,000-100,000 euros exhibits moderate evidence for adoption. By current European guidelines, the cost of 6,964 euros and 64,907 euros per QALY gained would give strong evidence for adoption of prolonged enoxaparin prophylaxis among total hip replacement patients, but moderate evidence for adoption among total knee replacement patients. Sensitivity analyses using 20% changes from the base-case analysis showed this outcome to be robust. CONCLUSIONS: Our findings indicate that, among patients undergoing elective total hip or knee replacement, prolonged enoxaparin prophylaxis leads to increased health benefits at increased cost. Given the additional costs that healthcare decision makers in Europe are usually prepared to pay for a gain in utility, prolonged prophylaxis with enoxaparin is cost-effective after elective total hip replacement, and our data provide strong evidence for adoption of prolonged enoxaparin prophylaxis after elective total hip replacement.

Anticoagulants↗
PubMed2003

Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.

BACKGROUND: Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer. METHODS: Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months). RESULTS: During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group. CONCLUSIONS: In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding.

Acenocoumarol↗
PubMed2005

An animal model for venous thrombosis and spontaneous pulmonary embolism.

STUDY DESIGN: An animal model. OBJECTIVE: To test the natural sequence of venous thrombosis and pulmonary thromboembolism experimentally. SETTING: Veterans Administration Hospital, USA. METHOD: In dogs, a venous thrombosis was induced in a isolated segment of the internal jugular vein by a 5 min exposure to sodium morrhuate and then re-establishing venous patency. A tracer, (125)I human fibrinogen, was administered through another vein 1 h prior to the end of each experiment when a blood sample, the venous thrombus, and the lungs were removed. Thrombi were described by age, weight, histology, and fibrin uptake (thrombus to blood radioactivity ratio, g/g). Pulmonary emboli (PE) were identified by autoradiography of lung slices or by microscopic examination of lung sections. RESULTS: Venous thrombosis developed in all experiments, duration 1-64, median 5 h (n=12). Histologically, younger thrombi were characterized by platelet aggregates surrounded by polymorphonuclear leukocytes (PMN), and uniform fibrin deposit; the older thrombi by platelet ghost cells, fewer PMN leukocytes, and broken fibrin strands and loops (n=6). Pulmonary thromboemboli were imaged as 'hot spots' in six of six experiments in which lung slices were autoradiographed and were identified microscopically in six of six experiments in which lung sections were taken. The number of PE diagnosed microscopically did not correlate with the age of the corresponding thrombus but was directly related to fibrin uptake (n=5, r=0.99, P<0.01). CONCLUSION: An animal model for venous thrombosis that generates pulmonary thromboembolism has been described.

Animals↗
PubMed1988

Physician practices in the treatment of pulmonary embolism and deep venous thrombosis.

To quantify physician practices in the care of patients with presumed pulmonary embolism or deep venous thrombosis, we analyzed heparin sodium orders, the intensity of anticoagulation, and complications in 65 patients with the diagnosis of deep venous thrombosis or pulmonary embolism. All patients were given heparin, for a mean (+/- SEM) period of 8.8 +/- 0.4 days. A high percentage of patients (60%) did not have a single partial thromboplastin time (PTT) greater than 1.5 times control within the first 24 hours of heparin therapy. Not until day 8 were 90% of PTTs in therapeutic range. We identified five common practices that led to delays in achieving a PTT greater than 1.5 times the laboratory control: (1) failure to start heparin therapy at the time of initial clinical suspicion, (2) choice of a heparin sodium bolus (mean, 5861 +/- 365 U) and continuous infusion (1026 +/- 148 U/h) insufficient to elevate the PTT to greater than 1.5 times control, (3) delay in obtaining the first PTT (mean, 11.7 +/- 1 h after start of heparin therapy), (4) insufficient heparin dosing in response to a low PTT, and (5) excessive and prolonged reductions in heparin therapy in response to a PTT greater than three times control, leading to subtherapeutic levels in 56% of subsequent PTTs. We think that poor understanding of heparin kinetics, overcautious behavior of physicians, and high heparin requirements in this selected population account for the findings.

Female↗
PubMed2001

Looking for deep vein thrombosis in suspected pulmonary embolism.

Pulmonary embolism (PE) and deep vein thrombosis are two facets of the same disease, that is, venous thromboembolism (VTE). In patients with angiographically proven PE, the prevalence of proximal deep vein thrombosis by venography is around 70%. The sensitivity of compression ultrasonography (US) for the diagnosis of acute VTE in patients with a suspicion of PE is between 40 and 60%, with a high specificity (96 to 100%). Taking into account the 20 to 30% prevalence of PE in a population consulting for suspicion of this disease, the first line use of compression US will allow the diagnosis of acute VTE in half of patients with confirmed PE, that is, in 10 to 15% of patients addressed for suspicion of PE. In outpatients, the first line use of D-dimers which will exclude acute VTE in one-third of the initial population will slightly increase the reliability of compression US as a first imaging test. New tools of looking for deep vein thrombosis, such as computed tomographic venography coupled with computed tomographic pulmonary angiography, could become an interesting approach in the diagnostic strategy of PE, but require adequate evaluation in prospective studies.

Biomarkers↗