Screening for occult cancer in patients with acute deep vein thrombosis or pulmonary embolism.

Patients with acute venous thromboembolism have an increased risk for occult malignancy. Limited screening for these malignancies has become common practice but little is known about its usefulness. This is a prospective cohort follow-up study in consecutive patients with acute venous thromboembolism. All patients underwent a routine clinical evaluation for malignancy, if negative, followed by a limited diagnostic work-up consisting of abdominal and pelvic ultrasound and laboratory markers for malignancy. Clinical follow-up was conducted to detect screening failures. The routine clinical evaluation was performed in 864 patients and revealed malignancy in 34 (3.9%) of them. Among the remaining 830 patients the limited diagnostic work-up revealed 13 further malignancies. During follow-up, cancer became symptomatic in 14 patients who were negative for cancer at screening (sensitivity of limited diagnostic work-up, 48.1%). Malignancies that were identified by the limited diagnostic work-up were early stage in 61% of cases vs. 14% in cases occurring during follow-up. Most patients with occult cancer had idiopathic venous thromboembolism and were older than 70 years. A limited diagnostic work-up for occult cancer in patients with venous thromboembolism has the capacity to identify approximately one-half of the malignancies. Identified malignancies were predominantly in an early stage.     

Is extensive screening for cancer in idiopathic venous thromboembolism warranted?

Summary. Background: Patients with a first episode of idiopathic venous thromboembolism (IVTE) have an estimated 10% incidence of cancer within 12 months after diagnosis. However, the utility of screening for cancer in this population is controversial. Methods: In this prospective concurrently controlled cohort study, limited and extensive cancer screening strategies were compared. All 630 patients underwent baseline screening consisting of history, physical examination, basic laboratory tests and chest X‐ray. In the extensive screening group abdominal and chest CT scan and mammography were added. Outcomes were incidence and curability of cancer, and cancer‐related and overall mortality. Results: In 12 of the 342 (3.5%) patients in the extensive screening group malignancy was diagnosed at baseline compared with 2.4% (seven of 288 patients) in the limited screening group. Extensive screening detected six additional cancers (2.0%; 95% CI, 0.74–4.3), of which three were potentially curable. During a median 2.5 years of follow‐up, cancer was diagnosed in 3.7% and 5.0% in the extensive and limited screening groups, respectively. In the extensive screening group 26 patients (7.6%) died compared with 24 (8.3%) in the limited screening group; adjusted hazard ratio 1.22 (95% CI, 0.69–2.22). Of these deaths 17 (5.0%) in the extensive screening group and 8 (2.8%) in the limited screening group were cancer related; adjusted hazard ratio 1.79 (95% CI, 0.74–4.35). Conclusions: The low yield of extensive screening and lack of survival benefit do not support routine screening for cancer with abdominal and chest CT scan and mammography in patients with a first episode of IVTE.     

Incidence of cancer after a first episode of idiopathic venous thromboembolism treated with 3 months or 1 year of oral anticoagulation

Summary.  Background : A prolonged treatment with oral anticoagulants has been claimed to reduce the incidence of newly diagnosed cancer in the long-term follow-up of patients with venous thromboembolism. Objectives : In a multicenter prospective study we assessed the incidence of newly diagnosed clinically overt cancer in patients with a first episode of idiopathic venous thromboembolism (VTE) treated with oral anticoagulants for 3 months or 1 year. Patients and methods : Consecutive patients with an idiopathic venous thromboembolism who had completed 3 months of oral anticoagulant therapy without having a recurrence, bleeding or newly diagnosed cancer were randomized to discontinue oral anticoagulant therapy or to continue it for nine additional months. Idiopathic venous thromboembolism was defined as thrombosis occurring in the absence of known cancer, known thrombophilia, or temporary risk factors for venous thromboembolism. All patients were followed up for at least 1 year after randomization. Results : A total of 429 patients, 265 patients with DVT and 164 with PE, were followed up for an average of 43.7 months after randomization. A newly diagnosed cancer occurred in 32 patients (7.5%), 13 (6.2%) of the 210 patients treated for 3 months and 19 (8.7%) of the 219 patients treated for 1 year (RR = 0.71, 95% confidence interval 0.36–1.41). Conclusions : The incidence of newly diagnosed clinically overt cancer is not reduced in patients with idiopathic venous thromboembolism treated with 1-year anticoagulant treatment compared with patients treated for 3 months.     

JAK2V617F mutation screening as part of the hypercoagulable work-up in the absence of splanchnic venous thrombosis or overt myeloproliferative neoplasm: assessment of value in a series of 664 consecutive patients

The JAK2V617F mutation is recurrent in polycythemia vera and essential thrombocythemia, which are myeloproliferative neoplasms (MPNs) frequently associated with arterial and/or venous thromboembolism. More recently, the JAK2V617F mutation has been identified as a surrogate marker for subclinical or "occult" clonal myeloproliferation in patients with splanchnic venous thrombosis. However, information is limited regarding JAK2V617F-associated thrombosis outside the splanchnic district in patients without overt MPN. To address this issue, we retrospectively studied a consecutive series of 664 such patients who experienced thrombotic events characteristic of an MPN (500 with venous thromboembolism, 136 with stroke, and 28 with myocardial infarction at a young age). The JAK2V617F mutation was detected in only 6 (<1.0%) patients (5 with recurrent venous thromboembolism and 1 with stroke), and the mutant allele burden was low in all instances (range, 2.2%-7.5%). None of these 6 patients developed either overt MPN or recurrent thrombosis after a median follow-up of 40 months. We conclude that the prevalence of the JAK2V617F mutation in patients with nonsplanchnic venous thrombosis in the absence of MPN is too low to warrant mutation screening as part of the hypercoagulable work-up. Our study also suggests that the natural history of a JAK2V617F-positive "occult" MPN might be different from that of a typical MPN.     

Venous thromboembolism in patients undergoing rehabilitation for stroke.

OBJECTIVE: To determine the incidence of venous thromboembolism during rehabilitation for stroke and to identify factors that alter its risk. DESIGN: Cohort. SETTING: Tertiary care stroke rehabilitation program. PATIENTS: 102 consecutive patients undergoing rehabilitation for stroke. INTERVENTIONS: Impedance plethysmography (IPG) as routine screening and in patients with symptoms of deep venous thrombosis (DVT). MAIN OUTCOME MEASURES: DVT, pulmonary embolism (PE), death from PE. RESULTS: Venous thromboembolism was documented in 11 patients (11%) an average of 60 days after stroke onset (range 14-138 days); 2 patients (2%) died from PE. DVT was found on routine IPG screening in six patients and verified by IPG in two clinically symptomatic patients. The odds of developing venous thromboembolism was 17.6 (95% confidence interval: 2.2-143.5) in patients who were bedridden or wheelchair-bound at the time of admission. CONCLUSIONS: The incidence of venous thromboembolism is high and greatest in bedridden or wheelchair-bound patients undergoing stroke rehabilitation; randomized trials evaluating the safety and efficacy of screening and/or prophylaxis in such patients are required.     

Deep Vein Thrombosis and Occult Cancer

In contrast to the established relation between known cancer and subsequent venous thromboembolism, the question of whether an association exists between venous thrombosis and the risk of subsequent overt cancer has remained without a convincing answer until 1992. A recent publication has provided a firm demonstration of this connection. Although this study has demonstrated a highly significant association between idiopathic vein thrombosis and subsequent overt malignant disease, firm recommendations for an extensive screening of cancer in all such patients cannot be made on the basis of these results.     

Venous thromboembolism and the risk of subsequent symptomatic atherosclerosis

BACKGROUND: Recently, we reported an association between asymptomatic carotid atherosclerosis and venous thromboembolism (VTE) of unknown origin. We hypothesized that patients with VTE of unknown origin would be at a higher risk of developing symptomatic atherosclerosis than patients with VTE induced by known risk factors. METHODS: To examine this hypothesis, we studied 1,919 consecutive patients followed prospectively after their first VTE episode. The primary outcome was non-fatal and fatal symptomatic atherosclerotic disease in patients with VTE of unknown origin as compared to those with secondary VTE. An independent committee assessed all study outcomes, and adjusted hazard ratios (HR) were calculated using the Cox's proportional hazards model. RESULTS: After a median follow-up of 48 and 51 months, respectively, at least one symptomatic atherosclerotic complication was detected in 160 of the 1,063 patients (15.1%) with VTE of unknown origin, and in 73 of the 856 (8.5%) with secondary VTE. After adjusting for age and other risk factors of atherosclerosis, the HR for symptomatic atherosclerotic complications in patients with VTE of unknown origin compared to those with secondary VTE was 1.6 (95% confidence intervals; CI: 1.2-2.0). When the analysis was restricted to patients without previous symptomatic atherosclerosis, the HR became 1.7 (95% CI: 1.1-2.4). CONCLUSIONS: Patients with VTE of unknown origin have a 60% higher risk of developing symptomatic atherosclerotic disease than do patients with secondary venous thrombosis.     

Decision analysis for cancer screening in idiopathic venous thromboembolism

BACKGROUND: The SOMIT trial randomized patients with idiopathic venous thromboembolism (IVTE) and without signs of cancer at routine medical examination, to extensive screening for cancer plus 2 years of follow-up or to just 2-year follow-up. METHODS: The data of the SOMIT-trial were used to perform a decision analysis. The screening tests were divided in several possible strategies. The number of detected cancer patients and the number of patients investigated further for an eventually benign condition were calculated for each strategy. The total costs for the screening strategy and for each detected cancer patient were determined. Based on the tumor type, stage, age and gender of the individual cancer patient, the difference in live years gained (LYG) was calculated between the two study groups. RESULTS: Computed tomography (CT) of the abdomen combined with sputum cytology and mammography detected 12 of the 14 patients with cancer and had one false-positive result. In general, screening strategies including abdominal/pelvic ultrasonography (US) or tumor markers yielded a higher number of patients needed to screen in comparison with those using abdominal/pelvic CT. Furthermore, the strategies which included colonoscopy, tumor markers, and abdominal/pelvic US were significantly more costly, had inferior LYG and higher costs per LYG, when compared with strategies using abdominal/pelvic CT. CONCLUSIONS: Despite the limitations of this analysis, the screening for cancer with a strategy including abdominal/pelvic CT with or without mammography and/or sputum cytology appears potentially useful for cancer screening in patients with IVTE. The cost-effectiveness analysis of this strategy needs confirmation in a large trial.     

Validation of the Canadian Clinical Probability Model for Acute Venous Thrombosis

OBJECTIVE: To validate the predictive value of the Canadian clinical probability model for acute venous thrombosis, which, to the best of the authors' knowledge, has not been done in emergency department (ED) settings outside of Canada. METHODS: Demographic and clinical information, rapid D-dimer testing, and venous ultrasound imaging were obtained among patients presenting with clinically suspected venous thrombosis at a university-affiliated ED. A diagnosis of deep venous thrombosis (DVT) was made based on venous ultrasound test results or objectively documented venous thromboembolism during a 12-week follow-up period. The probability of venous thrombosis was calculated using the Canadian clinical probability model. RESULTS: Among 102 patients, 17 (17%) were diagnosed as having venous thrombosis initially or during the three-month follow-up period. The frequency of venous thrombosis among patients categorized as having high probability was 10 of 17 [59%, 95% confidence interval (95% CI) = 35% to 82%], 6 of 44 (14%, 95% CI = 4% to 24%) with intermediate probability, and 1 of 41 (2%, 95% CI = 0.1% to 11%) with low probability. This compares with respective values of 49%, 14%, and 3%, reported by Canadian researchers in an ED study. Forty-one of 102 (40%) patients had an alternate diagnosis as likely or more likely than venous thrombosis, but only three (7%, 95% CI = 2% to 18%) of these had venous thrombosis. CONCLUSIONS: Use of the Canadian probability model for DVT in this ED resulted in effective risk stratification, comparable to previously published results.     

Epidemiology of venous thromboembolism in Asian patients undergoing major orthopedic surgery without thromboprophylaxis. The SMART Study

Summary.  Background:  In Asian patients undergoing surgery, the incidence of venous thromboembolism (VTE) is thought to be low relative to Western patients, and the routine use of thromboprophylaxis is controversial. Objectives:  The aim of this work was to study the epidemiology of VTE in Asian patients undergoing orthopedic surgery without thromboprophylaxis. Patients and methods:  We performed a prospective observational study of a cohort of consecutive Asian patients hospitalized for total hip or knee replacement or hip fracture surgery without thromboprophylaxis. The primary study outcome was the incidence of the composite of symptomatic VTE or sudden death at hospital discharge. This outcome was also assessed at 1 month's follow-up. Results:  Between April 2001 and July 2002, 2420 patients were enrolled. Median age was 68 years and the median duration of hospital stay was 13 days. The rate of symptomatic VTE or sudden death as notified by investigators was 2.3%[55 patients, 99% confidence interval (CI) 1.6, 3.2] and 1.2% (28 patients, 99% CI 0.7, 1.8) after adjudication by an independent committee. Chronic heart failure, varicose veins and a history of VTE were independent risk factors ( P <  0.05) for the occurrence of the primary endpoint. At 1 month's follow-up, the incidence of adjudicated symptomatic VTE or sudden death was 1.5% (35/2264 patients). Conclusion:  In Asian patients, the incidence of symptomatic VTE after major orthopedic surgery is not low, consistent with the rates observed in Western countries. The use of thromboprophylaxis should be considered in Asian patients undergoing such high-risk surgical procedures.     

Efficacy and safety of bemiparin compared with enoxaparin in the prevention of venous thromboembolism after total knee arthroplasty: a randomized, double-blind clinical trial

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

The post-thrombotic syndrome: risk factors and impact on the course of thrombotic disease

BACKGROUND: The post-thrombotic syndrome (PTS) is a frequent complication of deep vein thrombosis (DVT). Patients with recurrent ipsilateral DVT have an increased risk of PTS; other risk factors are unknown. OBJECTIVES: To establish risk factors of PTS and its impact on venous thrombotic disease. PATIENTS: We prospectively followed 406 patients after a first symptomatic DVT for a median of 60 months. Patients with recurrent DVT, a natural inhibitor deficiency, the lupus anticoagulant, cancer, long-term anticoagulation, an observation time < 18 months and DVT-recurrence prior PTS-assessment were excluded. Study outcomes were occurrence of PTS and recurrent symptomatic DVT. RESULTS: PTS was assessed after 44 +/- 23 months (mean +/- SD) using a clinical classification score. PTS developed in 176 of 406 patients (43.3%). Severe PTS was rare (1.4%). Proximal DVT was the strongest risk factor of PTS [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3-3.7]. Male gender (OR 1.6, 95% CI 1.0-2.8) and elevated D-dimer levels (OR 1.9, 95% CI 1.0-3.9) were weaker risk factors. Factor V Leiden, factor II G20210A or high factor VIII did not confer an increased risk of PTS. At 4 years, the cumulative probability of recurrence was 7.4% (95% CI 3.2-11.7) among patients with PTS when compared with 1.6% (95% CI 0-3.5; P < 0.02) among patients without PTS. The risk of recurrence was 2.6-fold (95% CI 1.2-5.9) increased when PTS was present. CONCLUSIONS: Proximal DVT, male gender, and high D-dimer levels are independently associated with the development of PTS in patients with a first DVT. Patients with PTS have an increased risk of recurrent venous thromboembolism.     

Optimizing breast cancer follow-up: diagnostic value and costs of additional routine breast ultrasound

A total of 2,546,325 breast cancer survivors are estimated to live in the United States. The organized breast cancer follow-up programs do not generally include breast ultrasound in asymptomatic women. The purpose of our prospective study was to investigate the efficacy of breast ultrasound in detecting previously occult recurrences. A total of 735 eligible patients with a history of breast cancer were recruited. We assessed the same patient population before (routine follow-up program) and after (study follow-up program) the introduction of an additional ultrasound examination. In the routine follow-up program 245 of 735 patients (33.3% [95% confidence-interval (CI): 29.9-36.7]) had an ultrasound due to abnormal local or mammographic findings. 490 of 735 patients (66.7% [95% CI: 63.3-70.1]) were initially considered asymptomatic and received an additional ultrasound exclusively within the study follow-up program.All positive examination results were followed by accelerated core needle biopsy. The routine follow-up program led to a biopsy in 66 of 735 patients (9.0%) revealing a recurrent cancer in 27 cases (3.7%). The study follow-up program with the additional ultrasound led to another 21 biopsies raising the total number of patients who had to undergo a biopsy from 9.0% (95% CI: 6.9-11.1) to 11.8% (95% CI: 9.5-14.2). Finally, we diagnosed a previously occult malignant lesion in an additional six patients following this protocol. Therefore, the rate of detected recurrences rose from 3.7% (95% CI: 2.3-5.0) in the routine follow-up program to 4.5% (95% CI: 3.0-6.0) in the study follow-up program (p = 0.041). Negative side effects were the additional costs (the costs per detected malignancy in the routine follow-up program were $2455.69; the costs for each additionally detected malignancy in the study follow-up program were $7580.30), the higher overall biopsy rate (9.0 vs. 11.8%) and the elevated benign biopsies rate (59.1% vs. 71.4%). Regarding these results, the advantages and disadvantages of additional breast ultrasound must be discussed for every follow-up patient individually even today, as we can detect a significantly higher number of previously occult malignancies. (E-mail s@wojcinski.de)     

Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor.

BACKGROUND: The risk of recurrence is lower after treatment of an episode of venous thromboembolism associated with a transient risk factor, such as recent surgery, than after an episode associated with a permanent, or no, risk factor. Retrospective analyses suggest that 1 month of anticoagulation is adequate for patients whose venous thromboembolic event was provoked by a transient risk factor. METHODS: In this double-blind study, patients who had completed 1 month of anticoagulant therapy for a first episode of venous thromboembolism provoked by a transient risk factor were randomly assigned to continue warfarin or to placebo for an additional 2 months. Our goal was to determine if the duration of treatment could be reduced without increasing the rate of recurrent venous thromboembolism during 11 months of follow-up. RESULTS: Of 84 patients assigned to placebo, five (6.0%) had recurrent venous thromboembolism, compared with three of 81 (3.7%) assigned to warfarin, resulting in an absolute risk difference of 2.3%[95% confidence interval (CI) - 5.2, 10.0]. The incidence of recurrent venous thromboembolism after discontinuation of warfarin was 6.8% per patient-year in those who received warfarin for 1 month and 3.2% per patient-year in those who received warfarin for 3 months (rate difference of 3.6% per patient-year; 95% CI - 3.8, 11.0). There were no major bleeds in either group. CONCLUSION: Duration of anticoagulant therapy for venous thromboembolism provoked by a transient risk factor should not be reduced from 3 months to 1 month as this is likely to increase recurrent venous thromboembolism without achieving a clinically important decrease in bleeding.     

The incidence and prognostic significance of elevated cardiac troponins in patients with submassive pulmonary embolism

Although the incidence and prognostic significance of elevated cardiac troponins are known in patients with massive pulmonary embolism (PE), few studies have addressed this issue in patients with hemodynamically stable, submassive PE, who comprise the majority of patients presenting with PE. This prospective cohort study was, therefore, designed to determine the incidence and prognostic significance of elevated cardiac troponins in patients with submassive PE. Consecutive patients with acute, symptomatic, submassive PE that was confirmed by objective diagnostic testing were studied. All patients received treatment with either unfractionated heparin or fondaparinux followed by a coumarin derivative and underwent clinical follow-up for 3 months. Cardiac troponin I (cTnI) levels were measured within 24 h of clinical presentation. An elevated cTnI was defined as > 0.5 microg L(-1) and indicated myocardial injury. Major myocardial injury, that is associated with myocardial infarction, was defined by a cTnI > 2.3 microg L(-1). The clinical outcomes were recurrent venous thromboembolism and all-cause death. In 458 patients with submassive PE, the incidence of cTnI > 0.5 microg L(-1) was 13.5%[95% confidence interval (CI): 10.4-16.7], and the incidence of cTnI > 2.3 microg L(-1) was 3.5% (95% CI: 2.0-5.6). An elevated cTnI > 0.5 microg L(-1) was associated with an increased risk of all-cause death [odds ratio (OR) = 3.5; 95% CI: 1.0-11.9], but did not appear to confer an increased risk of recurrent venous thromboembolism (OR = 1.1; 95% CI: 0.2-4.9). In patients who present with submassive PE, an elevated cTnI occurs in about one in seven patients and is associated with a 3.5-fold increased risk of all-cause death.     

Clinical outcome in patients with venous thromboembolism and hidden cancer: findings from the RIETE Registry

Summary.  Introduction:  Although extensive screening in patients with venous thromboembolism (VTE) may result in early identification of hidden cancer, it is unknown whether the prognosis of these patients may be favorably influenced. Patients and methods:  RIETE is an ongoing, prospective registry of consecutive patients with objectively confirmed, symptomatic, acute VTE. We compared the 3-month outcome of patients with hidden cancer with that in patients in whom no symptoms of cancer were noted. Results:  Of 17 475 patients with acute VTE, 2852 (16%) had cancer diagnosed before VTE or during admission. Hidden cancer was detected in 178 (1.2%) of the remaining 14 623 patients. The most common sites were lung, prostate, colorectum, or hematologic, and 51% had metastases. As compared with patients in whom no symptoms of cancer were noted, those with hidden cancer had an increased incidence of recurrent VTE (11.4% vs. 2.1%; P  <   0.001), major bleeding (5.1% vs. 2.1%; P  =   0.007), and mortality (20% vs. 5.4%; P  <   0.001). In the multivariate analysis, patients aged 60–75 years [odds ratio 1.8; 95% CI 1.2–2.7], with idiopathic VTE (odds ratio 3.0; 95% CI 2.2–4.2), with bilateral thrombosis (odds ratio 2.3; 95% CI 1.3–4.1) or with anemia (odds ratio 1.9; 95% CI 1.4–2.6) were at an increased risk for hidden cancer. Conclusions:  VTE patients with hidden cancer have an increased incidence of recurrences, major bleeding or death during the first 3 months of therapy. With four simple, easily obtainable variables, it is possible to identify a subgroup of VTE patients with a higher risk for hidden cancer.     

Spinal Cord Injury Risk Assessment for Thromboembolism (SPIRATE Study)

OBJECTIVE: To identify risk factors for venous thromboembolism (VTE) during the rehabilitation phase of spinal cord injury. DESIGN: A comprehensive review of the charts of all patients admitted between 1992 and 1995 for rehabilitation after spinal cord injury. Only records including evidence for objective testing for thromboembolism were included. The analysis variables included type and location of spinal cord injury, American Spinal Injury Association classification, concomitant injuries, surgical procedures, complications, preexisting illnesses, and use of antithrombotic prophylaxis. Hierarchically optimal classification tree analysis was employed to develop a nonlinear model for predicting deep vein thrombosis. RESULTS: The analysis sample consisted of these 243 persons with acute spinal cord injury, 51 of whom had venous thromboembolism, and eight of whom died. A three-variable model emerged that identified patient groups differing in relative likelihood of experiencing deep vein thrombosis. The highest likelihood group were patients with cancer over the age of 35 yrs. Women between the ages of 36 and 58 yrs without cancer were also at increased risk, as were cancer-free men with flaccid paralysis. CONCLUSIONS: Venous thromboembolism is more likely to develop in spinal cord injury patients who are older, obese, and have flaccid paralysis or cancer. These patients should receive vigorous prophylaxis against venous thromboembolism.     

The metabolic syndrome and the risk of venous thrombosis: a case–control study

OBJECTIVE: The results of recent studies have suggested that patients with idiopathic venous thromboembolism (VTE) might be at increased risk of asymptomatic atherosclerosis and cardiovascular events. The metabolic syndrome is a cluster of risk factors for atherosclerosis. Its impact on VTE is unknown. METHODS: In a case-control study, consecutive patients with objectively confirmed deep vein thrombosis (DVT) and control subjects with objectively excluded DVT underwent clinical assessment for the presence of the metabolic syndrome according to the National Cholesterol Education Program criteria. The presence of known risk factors for DVT was documented. Patients with DVT secondary to cancer were excluded. The prevalence of the metabolic syndrome was compared between patients with idiopathic DVT and controls. RESULTS: We enrolled 93 patients with a first episode of idiopathic DVT and 107 controls. The mean age was 65.1 and 63.7 years, respectively. The metabolic syndrome was diagnosed in 50.5% of patients with idiopathic DVT and in 34.6% of controls [odds ratio (OR) 1.93; 95% confidence interval (CI) 1.05, 3.56]. After adjustment for age, sex, body mass index, and smoke, the metabolic syndrome remained independently associated with idiopathic DVT (OR 1.94; 95% CI 1.04, 3.63). In patients with secondary DVT, the prevalence of the metabolic syndrome was 27%. CONCLUSIONS: The metabolic syndrome may play a role in the pathogenesis of idiopathic DVT and may act as link between venous thrombosis and atherosclerosis.     

Body mass index and mortality in patients with acute venous thromboembolism: findings from the RIETE registry

Summary.  Background:  There is little information on the influence of body mass index (BMI) on mortality in patients with acute venous thromboembolism (VTE). Patients and methods:  RIETE is an ongoing registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. We examined the association between BMI and mortality during the first 3 months of therapy. Results:  Of the 10 114 patients enrolled as of March 2007: 153 (1.5%) were underweight (BMI < 18.5); 2882 (28%) had a normal weight (BMI 18.5–24.9); 4327 (43%) were overweight (BMI 25.0–30); and 2752 (27%) were obese (BMI > 30). The overweight and obese patients were significantly older, and were less likely to have had cancer, recent immobility or renal insufficiency. After 3 months of therapy their death rates were 28%, 12%, 6.2% and 4.2%, respectively. In multivariate analysis, the relative risks for death after adjusting for confounding variables including age, cancer, renal insufficiency or idiopathic VTE were: 2.1 (95% CI, 1.5–2.7); 1.0 (reference); 0.6 (95% CI, 0.5–0.7); and 0.5 (95% CI, 0.4–0.6), respectively. The rates of fatal pulmonary embolism (2.0%, 2.1%, 1.2% and 0.8%, respectively) also decreased with BMI. There were no differences in the rate of fatal bleeding, but patients who were underweight had an increased incidence of major bleeding complications (7.2% vs. 2.7%; odds ratio, 2.7; 95% CI, 1.4–5.1). Conclusions:  Obese patients with acute VTE have less than half the mortality rate when compared with normal BMI patients. This reduction in mortality rates was consistent among all subgroups and persisted after multivariate adjustment.     

Epidemiology of venous thromboembolism after lower limb arthroplasty: the FOTO study

BACKGROUND: In view of recent substantial changes in the management of orthopedic surgery patients, a study was performed in order to update data on the epidemiology of venous thromboembolism (VTE) in patients undergoing lower limb arthroplasty according to contemporary practise. METHODS: We performed a prospective observational study of a cohort of consecutive patients hospitalized for total hip or knee replacement in June 2003. The primary study outcome was the incidence of symptomatic VTE at 3 months. All events were adjudicated by an independent critical event committee. RESULTS: Data from 1080 patients (mean age 68.0 years) were available; 63.2% were undergoing total hip replacement and 36.8% total knee replacement. Pharmacological thromboprophylaxis was administered for a mean time of 36 days. Injectable antithrombotics were used in more than 99% of patients, irrespective of the type of surgery. The incidence of the primary study outcome was 1.8% (20 events; 95% CI: 1.0-2.6%). The incidences were 1.3% and 2.8% in hip and knee surgery patients, respectively. There were two pulmonary embolisms, both in knee surgery patients; neither was fatal. Thirty-five per cent of VTEs occurred after hospital discharge. An age of at least 75 years and the absence of ambulation before hospital discharge were the only significant (P < 0.05) predictors of VTE. The rate of clinically significant bleeding was 1.0% and the rate of death was 0.9%. CONCLUSIONS: The incidence of symptomatic VTE after lower limb arthroplasty is low, even if there is still a need to improve thromboprophylaxis, notably in patients undergoing knee arthroplasty.