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Objective: To assess whether guidelines for the management of suspected PE, recommending that ventilation/perfusion (V/Q) scintigraphy should be followed by other imaging in case of non-diagnostic result, and interpreted along with the clinical probability, are applied in daily practice., Design: Two-year audit study., Setting: Tertiary hospital in France., Participants: All patients referred to the nuclear medicine department for a suspected pulmonary embolism (PE), with a low clinical probability, a positive D-Dimer test, and a low V/Q scintigraphy., Intervention: We reviewed medical records to collect data on further diagnostic strategy and therapeutic management., Main Outcome Measure: Thromboembolic risk during a three-month follow up in patients who did not undergo anticoagulation therapy on the basis of a negative diagnostic work up., Results: Of the 456 selected patients, PE was excluded on the basis of a low pretest probability and a low V/Q scintigraphy probability without further testing in 184 (group 1). In the other 272 patients (group 2), 4 venous thromboembolism (VTE) events were diagnosed by leg vein ultrasonography and/or computed tomography pulmonary angiography. In patients who did not receive anticoagulant treatment during follow up, one patient from group 1 (0.6%, 95% confidence interval 0.1 to 3.3) and two patients from group 2 (0.9%, 95% CI 0.2 to 3.2) had an acute venous thromboembolic event., Conclusion: Different attitudes are adopted by physicians in patients with a low clinical probability and a low V/Q scintigraphy probability, without impact on safety, as assessed by a non-significant difference in the three-month thromboembolic risks between these two groups.

Cohort studies suggest that exposure to antipsychotic agents may be associated with an increased risk of venous thromboembolism (VTE). Few data concerning antidepressant drugs are available. Using a different methodological approach, the aim of this study was to estimate the association between neuroleptic and antidepressant drug use and the risk of VTE. We report the results of a case-control study designed to evaluate interactions between acquired and inherited risk factors of VTE. We included 677 cases hospitalized with deep vein thrombosis and or pulmonary embolism with no major acquired risk factor for VTE, and 677 controls matched for gender and age. Drug exposure was defined as current use of drugs at admission. Neuroleptic exposure was associated with an increased risk of VTE (OR = 2.1, 95% CI 1.4-3.2). Among neuroleptics, antipsychotic agent use was associated with a 3.5-fold increased risk of VTE (OR = 3.5, 95% CI 2.0-6.2). No association was found between antidepressant drug exposure and the risk of VTE (OR = 1.1, 95% CI 0.9-1.5). In this hospital-based case-control study, exposure to antipsychotic drugs was associated with an increased risk of VTE. These results, added to previous results, suggest that clinicians should consider antipsychotic drug exposure as a potential risk factor of VTE. More studies are needed in order to further elucidate this adverse effect, and to determine the possible predisposing factors and the biological mechanisms involved.

Among candidate risk factors associated with postoperative venous thromboembolism (VTE), the role of factorV Leiden (FVL) mutation remains unclear. We performed a case-control study to assess the potential significance of FVL mutation in postoperative VTE cases despite prophylaxis. We used data from the ongoing case-control "EDITH" study. We extracted 133VTE cases and 144 controls who had undergone either surgery or had plaster cast in the previous three months. Prophylaxis adequacy with regard to the recommendations published by the American College of Chest Physicians was retrospectively assessed. FVL mutation was present in 20VTE cases and four controls (OR 5.9, 95% CI 2-18). Prophylaxis was judged as adequate in 116 cases (88.5%) and in 129 controls (87.2%) (p=0.66). The frequency of FVL mutation was not different in VTE cases occurring while on adequate prophylaxis and in VTE cases occurring after the end of adequate prophylaxis (p=0.27). FVL mutation was closely associated with postoperative VTE in patients classified as having received an adequate prophylaxis (8.4; 95% CI, 2.4 to 29). This study shows a close association between the presence of factorV Leiden mutation in symptomatic VTE occurring after surgery despite prophylaxis.

Background: Moderate hyperhomocysteinemia and factor V Leiden mutation are among the most prevalent risk factors for venous thromboembolism (VTE). The hypothesis of an interaction between those risks has been raised and conflicting results were reported., Methods: We designed a hospital-based case-control study to test the interaction between Factor V Leiden and fasting serum total homocysteine (tHcy). We have also analysed the G20210A prothrombin gene variant. This study enrolled 904 hospitalised patients who had an objectively proven deep vein thrombosis and/or pulmonary embolism as well as 904 hospitalised control patients matched for gender, age and major acquired risk factor for VTE., Results: Our data did not detect any multiplicative interaction between hyperhomocysteinemia (>15 mumol/L) and factor V Leiden mutation or G20210A prothrombin gene variant. Odds ratios (95% CI) were 4.0 (1.5-11) and 6.0 (1.3-27) for the combined effect of hyperhomocysteinemia with either factor V Leiden mutation or G20210A prothrombin gene variant, respectively., Conclusions: Current data provide further knowledge in relationship between hyperhomocysteinemia and inherited risk factors, such as factor V Leiden mutation and G20210A prothrombin gene variant. As those risk factors are not so rare among Caucasians, a better estimate of the risk related to double exposure might help to optimise venous thromboembolism prevention.

Background: D-dimer tests are used in various diagnostic strategies to exclude pulmonary embolism (PE). However, their role as an exclusionary first-line test is still uncertain, mainly because accuracy of the test varies according to the assay and the studied population., Methods: The aim of this multicentre study was to evaluate the accuracy of D-dimer testing in patients with suspected PE. Diagnosis of PE was based on pre-test clinical probability (PCP) evaluation and both single-detector spiral CT (CT) and lower limbs compression ultrasonography (CUS). Lung scanning and/or pulmonary angiography was mandatory when CT or CUS was inconclusive and when both CT and CUS were normal in a patient with a high PCP. All patients were followed-up for 3 months, looking for VTE recurrence. D-dimers were collected within 24 h of inclusion and stored in each local hematology unit, to be analyzed at the end of all inclusions; physicians in charge of the patient were blinded to D-dimer results., Results: Three hundred and fifty two patients were included in 4 centres. Prevalence of PE was 38.6%. PCP was low in 82 (23.3%), intermediate in 176 (50%) and high in 94 (26.7%) patients. Sensitivity of D-dimer was 96.3% (95% CI: 93-99) and negative predictive value reached 94.4% (95% CI: 90-99). Five patients with a confirmed PE had a D-dimer level below 500 ng/ml (two patients with a high PCP). Among 258 patients with low or intermediate PCP, 80 (31%) had a negative D-dimer test result; three of them had a false negative result and the number needed to test was 3.3. Among 94 patients with a high PCP, 9 had a negative D-dimer test result; two of them had a false negative result and the number needed to test was 13.5., Conclusion: These results confirm that rapid assays used in this study can safely exclude PE in first-line testing only in non-high CP patients.

Introduction: Fibrinogen Aalpha-Thr312Ala and Factor XIII Val34Leu polymorphisms have been shown to modify fibrin clot structure and function. However, clinical studies have yielded conflicting results on their possible association with venous thromboembolism (VTE)., Methods: We studied the association between these two polymorphisms and VTE in a hospital-based case-control study. We also assessed whether an independent or interactive association exists between Aalpha-fibrinogen Thr312Ala and FXIII Val34Leu polymorphisms and VTE. Fibrinogen Aalpha-Thr312Ala and FXIII Val34Leu polymorphisms were determined after PCR and restriction endonuclease digestion in 286 patients with idiopathic VTE and 286 age- and gender-matched controls. Results were analysed using a conditional logistic regression model for matched series., Results: The Fg-Aalpha 312Ala allele was associated with higher risk of VTE (OR 1.5; 95% CI: 1.1 to 2.2, p=0.01) while the FXIII 34Leu allele appeared protective (OR 0.7; 95% CI: 0.6 to 0.9, p=0.02). Both alleles demonstrated an independent association with idiopathic VTE after adjustment for Factor V Leiden and G20210A prothrombin polymorphisms. There was no interaction between the fibrinogen Aalpha-Thr312Ala and FXIII Val34Leu polymorphisms for the risk of VTE., Conclusion: In this case-control study, the fibrinogen Fg-Aalpha 312Ala allele was associated with an increased risk of VTE. The FXIII 34Leu allele was also significantly associated with a lower risk of VTE without any interaction between the two polymorphisms studied.

The factor V Leiden (FVL) mutation, a genetic abnormality with an autosomal mode of inheritance, is associated with an increased risk of venous thromboembolism (VTE). We aimed to determine the annual incidence of VTE in first-degree relatives of patients with VTE and FVL and to identify factors in patients and the relatives that influence this incidence. In this retrospective and prospective cohort study, the incidence of objectively diagnosed first episodes of VTE was assessed in 553 first-degree relatives of 161 patients with acute VTE and FVL. The annual incidence of VTE was 0.43% (95% CI, 0.3 to 0.56) with FVL and 0.17% (95% CI, 0.07 to 0.27) without FVL (relative risk of 2.5,95% CI, 1.3 to 4.7). A majority (70%) of episodes of VTE were provoked, and this proportion was similar with and without FVL. A larger proportion of VTE was provoked in women (83%) that in men (33%), with the difference accounted for by pregnancy and use of oral contraceptives. The proportion of pregnancies complicated by VTE was 3.9% (95% CI, 2.0-5.8) with FVL and 1.4% (95% CI, 0.04-2.7) without FVL. FVL is associated with a two- to threefold increase in VTE in first-degree relatives of patients with VTE. No subgroup of relatives was identified who require more than routine prophylaxis because of a particularly high risk of VTE.

Introduction: Although the advent of multi-detector row computed tomography (CT) has enabled better visualization of subsegmental pulmonary (SSP) arteries, SSP embolism is of uncertain clinical significance. We aimed at answering the following questions: Is spiral CT an accurate method to detect SSP embolism? How are subsegmental perfusion defects managed in outcome studies including spiral CT? What are the main characteristics and outcomes of patients in whom CT detects isolated subsegmental defects?, Methods: We performed a Medline search on July 1, 2004, using the keywords 'pulmonary embolism' and 'computed tomography'. We limited our search to English language prospective studies comparing CT to pulmonary angiography, and to prospective outcome studies including CT in a diagnostic strategy, with at least a 3-month follow-up., Results: Fourteen studies comparing CT to pulmonary angiography, and five prospective management studies using CT were retrieved. The sensitivity of single-detector CT for detecting subsegmental defects compared with pulmonary angiography was low (25%). The proportion of isolated SSP images was significantly higher in management studies using multi-detector CT (17 of 770 scans, 2.2%) compared with those using single-detector CT (22 of 2232, 1.0%; P = 0.01). No straightforward attitude regarding anticoagulation therapy for isolated subsegmental defects emerged from the available literature. Finally, important clinical differences were found between patients having subsegmental and segmental or more proximal defects., Conclusions: These findings underline the uncertainty regarding the clinical significance of SSP embolism, and the management of patients with such findings.

Background: Moderate hyperhomocysteinemia and B vitamins deficiency are thought to be risk factors for venous thromboembolism (VTE). The causality and independence of those associations are still questioned., Methods: We measured fasting serum total homocysteine, folates, and vitamin B12 levels as well as 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T genotypes in 467 patients hospitalized with a first well-documented deep vein thrombosis and/or pulmonary embolism not related to a major acquired risk factor and 467 controls matched for gender and age., Results: Mild hyperhomocysteinemia, low serum folates, and vitamin B12 were associated with VTE independently of each other. In multivariate analysis, odds ratios (OR) (95% CI) for VTE associated with mild hyperhomocysteinemia (>15 micromol L(-1)), low serum folates (< or = 4.9 nmol L(-1)), and vitamin B12 (< or = 253 pmol L(-1)) were 1.48 (1.05-2.08), 3.14 (1.35-7.32) and 1.42 (1.03-1.98), respectively. An MTHFRC677T genotype was not significantly associated with VTE; OR (95% CI): 1.13 (0.70-1.81), Conclusions: The current data provides further knowledge in the complex relationship between hyperhomocysteinemia, low vitamin levels, and VTE.

Objective: To achieve a common strategy in the event of a suspected venous thromboembolism., Design: A multifaceted intervention, combining an audit strategy and implementation of local guidelines: phase 1, the first step, consisted of a 6-month audit to identify dysfunction; during phase 2, intervention, local guidelines were formulated by a working group and then implemented; phase 3 consisted of a re-audit over a 6-month period following the intervention., Setting: A tertiary hospital, France., Participants: 419 patients with suspected venous thromboembolism in phase 1; 287 patients with suspected pulmonary embolism in phase 3., Results: First phase: a dysfunction was observed in three of five criteria under study: (i) the diagnostic procedure lasted more than 48 hours in 114 patients (27.2%); (ii) no anticoagulant therapy at the time of suspicion in 116 patients (27.7%); (iii) an inconclusive lung scan without further testing in the event of a suspected pulmonary embolism in 40 patients (14%); the intervention phase was thus restricted to the management of suspected pulmonary embolism; similar results were found during the phase 3 re-audit., Conclusion: No improvement in the diagnostic work-up in the event of a suspected pulmonary embolism was observed following this multifaceted intervention.

As the prevalence of PE increases with age, the effect of age on the diagnostic work-up in front of a clinical suspicion of PE deserves exploration. In this retrospective analysis, we used the data from 1041 consecutive suspected PE patients. The patients were divided into three groups according to tertiles of age: under 54 years, 54 to 73 years and above 73 years. The prevalence of PE in patients with respectively low, intermediate and high pretest clinical probability was expressed within each age group. We studied the effect of age on the results observed in three main groups of patients, after performing CT scan and ultrasonography (CUS): (1) patients with inconclusive results; (2) patients with negative findings on both exams and non high pretest clinical probability; (3) patients with positive findings.The prevalence of PE increased significantly with age, in overall, as well as in patients with low or intermediate pretest clinical probability. An analysis according to the three main diagnostic groups showed that: (1) the distribution of inconclusive spiral CT or CUS examinations was not different between age groups; (2) no thromboembolic event occurred in untreated patients with low or intermediate clinical probability aged under 54 years of age, whereas 7 events were diagnosed in patients aged over 73 years (p<0.001); (3) a higher proportion of older patients had a positive result at both spiral CT and CUS examinations. The percentage of positive CT scans in the case of negative or inconclusive CUS results was not different between age groups; conversely, in the case of a negative or inconclusive CT scan, the percentage of positive CUS was higher in older patients. In conclusion, management of elderly suspected PE patients appears to be different from both the work-up and the outcome perspectives.

Objective: To search for a link between Chlamydia pneumoniae serological status and venous thromboembolic disease., Methods: From March 1992 to October 1999, we conducted a cross-sectional hospital-based study of consecutive unselected outpatients referred to us for clinical suspicion of venous thromboembolism. We compared the Chlamydia pneumoniae serological status with respectively, the venous thromboembolism, the deep vein thrombosis and the proximal deep vein thrombosis status., Results: Among 1193 patients registered for suspected venous thromboembolism, 1010 samples were available (499 negative and 511 positive patients for venous thromboembolism). Seventy-nine patients were Chlamydia pneumoniae positive. Our work failed to demonstrate any clear association between Chlamydia pneumoniae and venous thromboembolism status. Nevertheless, we identified a statistical difference regarding Chlamydia pneumoniae seropositivity and proximal vein thrombosis status (adjusted odds ratio of 1.70, CI95%: 1.05 to 2.77)., Conclusion: The presence of Chlamydia pneumoniae antibodies might be a minor risk factor for venous thrombosis.

Previous studies of selected patients have suggested a reduction in the risk of venous thromboembolism with the use of statins. The objective of this study is to evaluate the influence of statin use on the risk of venous thromboembolic (VTE) events. The study is a case-control study (EDITH: Etude des Déterminants et Interactions de la Thrombose Veineuse), designed to investigate the genetic and environmental risk factors of VTE. A total of 377 patients consecutively hospitalized in the Brest University Hospital for a documented VTE event, between May 2000 and May 2002, and 377 age- and sex-matched controls were studied. Statin use was associated with a 58% decreased risk of VTE [odds ratio (OR) 0.42; 95% confidence interval (CI) 0.23-0.76; P = 0.002]. Adjustment for age, gender, coronary heart disease, atherosclerothrombotic disease or current use of aspirin did not alter the result. Neither fibrates (OR 1.38; 95% CI 0.76-2.52; P = 0.26), nor thienopyridines (OR 1.07; 95% CI 0.48-2.41; P = 0.85) were associated with a reduced risk of VTE. Aspirin use tended to decrease the risk of VTE, but this result was not significant (OR, 0.66; 95% CI, 0.42-1.05). The use of statins is associated with a significant reduction in the risk of VTE, irrespective of age, gender, and past history of atherosclerothrombotic disease, as well as the use of aspirin. This possible protective effect of statins warrants further investigations.

Numerous large randomized controlled trials have assessed the benefit of prophylactic anticoagulation for venous thromboembolism in selected patients. However, few trials were conducted in elderly patients, as this issue was not addressed in this specific population,or as elderly patients were excluded of these studies. Therefore, as the risk of a first episode of venous thromboembolism (in surgical and in medical setting) and the risk of a major anticoagulant-related bleeding are both increased in elderly subjects, the results of the main available studies can not be extrapolated to this population. Consequently, in practice, the balance between expected benefit and risk of prophylactic anticoagulation should be carefully assessed for each individual elderly patient taking in account the specific risk of venous thromboembolism in elderly in the absence of anticoagulation, the risk of anticoagulant related bleeding according to the type of anticoagulant treatment and the intrinsic risk of bleeding of elderly subjects and, lastly, the available guideline recommendations. In order to improve such evaluation, it is anticipated that further prophylactic studies are needed in elderly patients. In addition, the development of anticoagulation clinics and new oral anticoagulants should help to reduce anticoagulant related bleeding for an equivalent, or an increased, benefit.

Objective: To evaluate the diagnostic performance of transthoracic sonography of the lung in view of an acute suspicion of pulmonary embolism., Methods: The diagnosis of pulmonary embolism was made within 48 hours of admission with the use of a validated strategy that combined a lung scan, lower limb sonography, helical computed tomography, and pulmonary angiography in 74 consecutive patients. All patients had a 3-month follow-up. Transthoracic sonography of the lung and pleura was performed in a blinded fashion by investigators unaware of the diagnostic process. It was interpreted as suggestive or not suggestive of pulmonary embolism on the basis of previously published descriptions. The results were kept apart from the patient files until the end of the study., Results: Pulmonary embolism was confirmed in 31 (42%) of the 74 patients. None of the patients classified as pulmonary embolism-negative had a thromboembolic event during the 3-month follow-up. The diagnostic performance of transthoracic sonography was as follows: sensitivity, 71% (95% confidence interval, 52%-85%); specificity, 77% (95% confidence interval, 61%-88%); positive predictive value, 69% (95% confidence interval, 50%-83%); and negative predictive value, 79% (95% confidence interval, 63%-89%). The finding of an isolated pleural infarction was significantly more frequent in pulmonary embolism-positive patients compared with pulmonary embolism-negative patients (P = .0001)., Conclusions: The results from this study suggest that transthoracic sonography of the lung does not fulfill satisfactory performance criteria in view of a clinical suspicion of pulmonary embolism.

Unlabelled: AN IMPORTANT SUBJECT: The thromboembolic disease still prevails in the context of surgery, despite the progression in prophylaxis. Particular attention must be paid to the possibility of delayed events, often occurring within the three months following a surgical procedure. Although many general studies, assessing supplementary examination or diagnostic strategies are available, the proportion of patients concerned by a post-operative context varies., In Practice: The Doppler is the diagnostic examination of choice in the case of suspected deep vein thrombosis, but it is not recommended in a strategy of screening for asymptomatic thrombosis in surgery. A suspected embolism can be confirmed or eliminated using noninvasive examinations, but it requires that invasive tests be performed more often than in a medical context. The indication for a helical computed tomography, presently more readily available than a pulmonary angiography, would appear legitimate, so long as a Doppler of the lower limbs is systematically associated. RESERVATIONS IN THE POST-OPERATIVE PERIOD: The results of this strategy, most satisfactory in the majority of patients, do not appear as interesting post-operatively. The studies targeting the management of suspected post-operative pulmonary embolism are rare and warrant further encouragement.

The prevention of venous thromboembolism in medical patients remains questioned. All consecutive outpatients admitted in our medical unit were considered for inclusion in this study which aimed to estimate the prevalence of asymptomatic venous thrombosis on admission and the incidence during hospital stay. Exclusion criteria were: age <18 years, suspicion of venous thromboembolism, stay <4 days, ongoing anticoagulant therapy. Venous compression ultrasonography of the lower limbs was performed within 48 h. 234 patients were included. The prevalence of asymptomatic deep vein thrombosis on admission and the incidence during hospital follow-up were respectively 5.5% (95% confidence interval, 3.1 to 9.5%) and 2.6 per 1,000 person-days (95% confidence interval, 0.0 to 5.2). The prevalence and the incidence reached respectively 17.8% (95% confidence interval, 8.5 to 32.6%) and 6.0 per 1,000 person-days (95% confidence interval, 0.0 to 12.7) among patients over 80 years. A high prevalence of asymptomatic deep vein thrombosis on admission was suggested particularly among elderly medical patients.

Objective: to assess the effects of an educational program in asthmatic patients, following treatment readjustment., Methods: moderate to severe asthmatic adults underwent a run-in period (up to 45 days) in order to optimize their treatment. Patients were then randomized to an educational or control group over a one-year period. Education consisted of five individual sessions covering: pathophysiology of asthma, role of medication and side-effects, asthma triggers and their avoidance, detection of an asthma flare-up, and self-management plan based on symptoms and peak-flow monitoring. MAIN OUTCOME CRITERION: symptom-free days over the study period (SFD)., Results: a total of 72 patients were enrolled (36 in the "education group" and 36 in the "control group"), 54 of whom completed the study. Mean SFD was comparable in the two groups (88% in the education group and 89% in the control group, respectively). When the analysis was restricted to the education group, those patients who complied perfectly with the action plan (n = 5) exhibited a higher SFD, compared to the others (97% vs. 87%, p = 0.009)., Conclusion: both education and control groups showed high and comparable percentages of SFD. Compliance with self-management plans appears to be an important determining factor in educational programs.

D-dimer testing is useful for the exclusion of acute venous thromboembolism (VTE). Anticoagulant therapy is expected to reduce D-dimer levels in patients with thrombosis and, consequently, it may not be safe to use D-dimer levels to exclude VTE after anticoagulant therapy has been started. The objectives of this study were to estimate the decrease in D-dimer levels after 24 h of heparin therapy and, applying this estimate to the results of a recent study, to calculate the expected reduction in sensitivity. Using pre-defined criteria, we first performed a literature review to determine whether, and by how much, D-dimer levels decrease within 24 h of starting heparin therapy in patients with acute VTE. Using D-dimer levels that were measured in a prospective study of patients with confirmed deep vein thrombosis and/or pulmonary embolism as baselines, we then determined the change in sensitivity (and specificity) that would result from the fall in D-dimer levels that the literature review suggested would have occurred after 24 h of heparin therapy. On the basis of the literature review, we calculated that mean D-dimer levels decrease by 25%, 24 h after starting heparin therapy in patients with acute VTE. This 25% decrease in D-dimer levels resulted in a decrease in sensitivity from 95.6% (95% confidence interval, 90.0-98.6) to 89.4% (95% confidence interval, 83.7-95.1). There is a decrease in D-dimer levels in patients with acute VTE 24 h after starting heparin therapy that is expected to result in a clinically important drop in sensitivity.

This article aims to examine educational strategies in the context of the overall management of the asthmatic patient. The objectives are analysed from the viewpoints of the both the patient and the health care professionnal. The complexity of the manifestations of asthma and the variability of perception of symptoms require a personalised approach to education. The asthmatic patients, co-operation with their therapeutic management, in particular in matters of compliance, reveals problems common to other chronic conditions. If an agreement can be reached during an exchange of beliefs and points of view, this will lead to the most appropriate choice of therapy. The evaluation of educational strategies has been the subject of many publications and sequential studies must be distinguished from randomised controlled trials. Sequential studies of educational strategies generally include severe asthmatics, previously under-treated. The improvement in measured parameters of morbidity is often striking but it is difficult to separate the true effect of education from that of improved total management, particularly the introduction of preventative treatment. Randomised trials with an "uneducated" control group give more conflicting results. A particular emphasis may be placed on action plans based on monitoring of peak flow and/or symptoms. Finally the inclusion of educational strategies in the training programmes of health care professionnals is now well established and its impact should be evaluated.

Background: Low molecular weight heparin is as effective and safe as unfractionated heparin for treatment of acute venous thromboembolism. It is uncertain whether low molecular weight heparin should be administered once-daily or twice-daily in this setting., Method: A meta-analysis of randomized studies which directly compared once- and twice-daily administration of low molecular weight heparin for the treatment of acute venous thromboembolism was performed. A literature search was performed using Advanced Pub Med and the Cochrane library database, and abstracts from recent meetings were reviewed. Two investigators extracted data independently., Results: Five studies, involving 1522 patients, were eligible. There were no statistically significant differences in the frequencies of symptomatic (odds ratio, 0.85 in favor of once-daily therapy at three months, p = 0.6), and asymptomatic, recurrent venous thromboembolism, total and major bleeds (odds ratio, 1.16 in favor of twice-daily therapy at 10 days, p = 0.8); and death, at 10 days, as well as at three months of follow-up., Conclusion: Once-daily low molecular weight heparin appears to be as effective and safe as twice-daily administration for the acute treatment of venous thromboembolism. However, there is inadequate data from studies that directly compared once-daily and twice-daily administration to be able to exclude the possibility of a higher frequency of fatal bleeding with once-daily therapy.

A 41-year-old man who had been taking pravastatin for two years developed hypersensitivity pneumonitis. The initial examination found intestinal pneumonitis and hypereosinophilia. The patient's syndromes gradually resolved with withdrawal of pravastatin. As HMG coenzyme A reductase inhibitors are commonly prescribed, any respiratory symptoms in this setting should be considered with special attention.

HEPARINS: For unfractionated heparins, certain studies have demonstrated increased hemorrhage rates correlated with age and with renal function. Subcutaneous injections every 12 hours are as effective and less uncomfortable for the patient than continuous intravenous infusions. Low-molecular-weight heparins are currently contraindicated for curative treatment and their use is not recommended for prevention when the creatinine clearance is below 30 ml/min. OTHER ANTICOAGULANTS: The dosage of sodium daparanoid should be adapted to the renal function with regular surveillance of anti Xa activity. With hirudin, there is a risk of product accumulation in case of renal failure. For oral anticoagulants the relationship between old age and the frequency of hemorrhagic complications is still a subject of debate. ORAL ANTICOAGULANTS: The starting dosage should be reduced to one-half or one-quarter of the usual dose. The INR should be measured regularly, particularly since elderly subjects are highly susceptible to wide variations in INR irrespective of the cause. It is also advisable to carefully determine appropriate situations when oral coagulants should be used.

Unlabelled: RISK AND BENEFIT: The beneficial effect of anticoagulant treatment is well established by numerous therapeutic trials demonstrating its usefulness in two main indications (venous thromboembolism and complete arrhythmia due to atrial fibrillation) in selected populations. Very few trials have been specifically conducted in elderly subjects and the increased risk of thrombosis and anticoagulant related bleeding cannot be used to extrapolate the results to elderly subjects. For this reason, a careful assessment of the initial risk and expected benefit must be made for each individual patient using a validated and systematic global evaluation system adapted for elderly subjects in order to better discern the indications and the risk of hemorrhage., Perspectives: The development of anticoagulation clinics, based on the method initiated by Professor Boneu at Toulouse, together with clinical trials designed to produce results transposable to the diverse and complex geriatric population, and finally the development of new oral compounds not requiring laboratory tests under the same conditions should help reduce the therapeutic risk for an equivalent benefit.

Most patients who present with deep vein thrombosis (DVT) can be treated with weight-adjusted, fixed-dose, low molecular heparin as an outpatient. The subsequent duration of oral anticoagulant therapy should be individualized according to the risk of recurrent venous thromboembolism and the risk of anticoagulant-induced bleeding. The risk of recurrence is low if thrombosis was provoked by a major reversible risk factor such as surgery; 3 months of treatment is usually adequate for such patients. The risk of recurrence is high if thrombosis was unprovoked ("idiopathic") or associated with a nonreversible risk factor such as active cancer; at least 6 months, and sometimes indefinite, anticoagulant therapy is indicated for such patients. The presence of an antiphospholipid antibody, and other selected thrombophilic states, favors more prolonged therapy within each of the categories noted previously. Systemic thrombolytic therapy helps to restore venous patency and probably reduces the risk of the postthrombotic syndrome; however, it is associated with an unacceptable risk of bleeding. Catheter-directed thromboylsis, particularly for isolated iliofemoral thrombosis, may be beneficial and needs further evaluation in controlled trials.

Anticoagulation is the corner stone of therapy for venous thromboembolism. The optimal duration of this therapy depends on the balance between the risk of recurrent thrombosis if anticoagulants are stopped, and the risk of bleeding if patients remain on treatment. The risk of recurrence is low if thrombosis was precipitated by a major reversible risk factor such as surgery. Patients with idiopathic thrombosis (no apparent risk factor) and those with persistent risk factors (eg, cancer), have a high risk of recurrence. Some hereditary (eg, protein C, protein S or antithrombin deficiency; homozygous factor V Leiden) and acquired (eg, antiphospholipid antibodies) thrombophilic states are also risk factors for recurrence. Three months of anticoagulation is recommended when the risk of recurrence is low, whereas the duration of therapy should be extended to 6 months or longer when this risk is high, depending on the balance between the risk of recurrence and the risk of bleeding in each individual patient. Heparin preparations, at doses intermediate to those used for the acute treatment of venous thromboembolism and for primary prophylaxis, are an alternative to oral anticoagulants during the maintenance phase of treatment.

RECURRENT THROMBOSIS VERSUS ANTICOAGULANT-RELATED BLEEDING: The optimal duration of anticoagulation for venous thromboembolism depends on the balance between the risk of thrombosis if anticoagulation is stopped, and the risk of bleeding if patients remain on treatment. In the past decade, five large well designed trials have been completed which have compared different durations of anticoagulation for the treatment of various categories of patients with venous thrombosis. In conjunction with the findings of a number of other prospective studies, these trials have helped to identify risk factors for recurrent venous thrombosis and anticoagulant-related bleeding, and have led to a better understanding of the optimal duration of therapy for individual patients. RISK OF RECURRENT THROMBOSIS: The risk of recurrent thrombosis is low if thrombosis was precipitated by a major reversible risk factor such as surgery. Patients with idiopathic thrombosis (no apparent risk factor) and those with persistent risk factors (e.g., cancer), have a high risk of recurrence. Some hereditary (e.g., protein C, S or antithrombin deficiency) and acquired (e.g., antiphospholipid antibodies) thrombophilic states are risk factors for recurrence independently of whether thrombosis was, or was not, provoked by a major risk factor. DURATION OF THERAPY: Patients with a low risk of recurrence should be anticoagulated for three months. Others should be treated from 6 months to indefinitely, depending on the balance between the risk of recurrence and the risk of bleeding in each individual patient.

Background: Many studies have suggested an increased risk of venous thromboembolism (VTE) in patients with mild hyperhomocysteinemia. The C677T mutation in the MTHFR gene has recently been described as a cause of mild hyperhomocysteinemia., Objectives: To investigate the potential of the C677T mutation in the MTHFR gene in its homozygous state as a risk factor for VTE., Methods: Case-control study design. The presence of the mutation was determined in all consecutive patients referred from July 1994 to September 1997 and in whom the diagnosis was duly confirmed. Analysis was carried out in a subgroup of VTE patients free from both acquired and genetic risk factors (factor-V mutation and/or prothrombin gene mutation). A control group consisted of 105 volunteer blood donors., Results: In the 366 patients with a confirmed VTE, 253 presented acquired risk factors and 58 were carriers of the factor-V Leiden mutation and/or G20210A mutation of the prothrombin gene. In the remaining 55 patients, VTE was considered as 'unexplained', and the frequency of the C677T mutation MTHFR was 21.8% in its homozygous state and 34.5% in its heterozygous state. In the control group, 9.5% were found homozygous and 34.3% heterozygous. The odds ratio for having VTE in the presence of the mutation in its homozygous state was 2.9 (95% CI 1. 0-8.6)., Conclusion: This study suggests that the homozygous C677T mutation in the MTHFR gene might be a risk factor of VTE in patients with spontaneous events and without other common genetic risk factors., (Copyright 2000 S. Karger AG, Basel)

Venous thromboembolism is a frequent and potentially severe ailment in medical patients; the clinical signs are unreliable and as early detection of the thrombosis process by non-invasive techniques is not available, prevention appears to be an alternative. Careful definition of the medical situations at risk from venous thromboembolism is necessary. Age, prior history of venous thromboembolism, and immobilization constitute high risk circumstances. Analysis of the published studies advocates prevention in three circumstances: myocardial infarction, stroke and intensive care. In other cases, further controlled studies, randomized versus placebo, are needed.

We report a case of plastic bronchitis occurring in a 58 year-old man free from underlying pulmonary disease. Relief of symptoms was observed under steroid therapy (1 mg/kg), but relapse occurred as treatment being tapered. Such evolution is in accordance with recent published data.