Incidental venous thromboembolism in cancer patients: prevalence and consequence

Introduction

Careful re-evaluation of CT-scans for cancer staging frequently reveals unsuspected venous thromboembolism (VTE) on CT-scans. However, it is unknown how often these findings lead to anticoagulant treatment in daily clinical practice.

Methods

Reports from thoracic and/or abdominal CT-scans performed in a consecutive series of patients to stage cancer were retrospectively evaluated to determine the prevalence of incidental venous thromboembolism (iVTE). Presence of pre-existing signs of VTE, anticoagulant treatment and 3-month follow-up were analysed in patients with iVTE.

Results

A total of 1466 staging scans (838 patients) from the year 2006 were included in the analysis. The prevalence of VTE in patients was 2.5% (21/838 patients, 95% confidence interval 1.6-3.8%); the prevalence of VTE on scans was 1.4% (21/1466 scans, 95% CI 0.9-2.2%). Incidental PE or deep vein thrombosis (DVT) was observed in 11 (1.3%, 0.7-2.3%) and abdominal vein thrombosis in 9 patients (1.1%, 0.6-2.0%; in the portal (5), mesenteric (3) and renal vein (1), respectively). Nine out of eleven patients with PE/DVT were treated with anticoagulants, while none of the patients with thrombosis in other locations received anticoagulants. One of these patients developed symptomatic PE one month later; otherwise, follow up was uneventful in the untreated patients.

Conclusion

The prevalence of iVTE in patients with cancer in clinical practice is relatively low and most patients with PE or DVT are treated with anticoagulants. For patients with thrombi in other locations, further research is necessary to understand the natural history of these thrombi in order to develop adequate guidelines.     

The MASTER registry on venous thromboembolism: description of the study cohort

INTRODUCTION: Information on the epidemiology and long-term clinical outcome of venous thromboembolism (VTE) is mainly based on data from clinical trials and thus may be not representative of the full spectrum of VTE patients. The aim of this multicenter registry (MASTER) was to prospectively collect data on the epidemiology and long-term clinical outcome of VTE in an unselected cohort of patients. MATERIALS AND METHODS: In symptomatic patients with objectively confirmed acute VTE, information about clinical presentation, diagnostic methods, temporary and permanent risk factors, pre-event prophylaxis and treatment were captured by an electronic data network at the time of the index event. A 24-month follow-up is currently ongoing. RESULTS: From January 2002 to October 2004, 2119 patients were included in the MASTER registry in 25 Italian centers. At entry, the mean patient age was 59.3+/-18.1 years (range 18-99 years). 1541 patients (72.7%) were affected by deep vein thrombosis, 206 patients (9.7%) by pulmonary embolism and 372 patients (17.5%) by both deep vein thrombosis and pulmonary embolism. 676 patients (31.9%) received home-treatment. 899 patients (42.4%) had one or more temporary risk factors. 381 patients (18.0%) had a known cancer at the time of the index event and in 50 patients (2.4%) a new cancer was discovered at the time of the index event. 311 patients (14.7%) had a previous VTE. CONCLUSIONS: Following a real world approach, our registry describes the clinical presentation, risk factors, diagnosis and treatment procedures in a large cohort of unselected patients with VTE.     

Old and new oral anticoagulants for venous thromboembolism and atrial fibrillation: a review of the literature

Heparin, fondaparinux and vitamin K antagonists (VKAs) are effective for the prevention and treatment of venous thromboembolism. VKAs reduce by almost 60% the rate of cardioembolic complications in patients with atrial fibrillation. The risk for bleeding and the inconvenience for laboratory monitoring, dose adjustment and drug or food interactions are the main limits for VKAs while parenteral administration is the main limit for heparin and fondaparinux. New oral anticoagulants with more predictable anticoagulant response and no need for laboratory monitoring have been shown to be effective for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in patients with atrial fibrillation. The pharmacokinetic and pharmacodynamic profile of the new agents differ for mechanisms of action - mainly anti Xa and one antithrombin agent- bioavailability, half life, renal or live clearance. Drug interactions have been described with the new agents and inhibitors or inducers of P-gp or CYP3A4. Overall, in the prevention of venous thromboembolism after major elective orthopaedic surgery dabigatran was shown to be non-inferior, rivaroxaban and apixaban to be superior to enoxaparin. Both, rivaroxaban and dabigatran were shown to be non-inferior to low-molecular weight heparin and VKAs for the treatment of venous thromboembolism. Dabigatran 150 mg twice daily reduced the incidence of both ischemic and hemorrhagic stroke in patients with atrial fibrillation respect to warfarin. In these patients rivaroxaban and apixaban reduced the incidence of hemorrhagic stroke with a similar incidence of ischemic stroke. No bleeding concern emerged with the new anticoagulant agents in this indication.     

A pilot study utilizing whole body 18 F-FDG-PET/CT as a comprehensive screening strategy for occult malignancy in patients with unprovoked venous thromboembolism

Background

Approximately 7-10% of patients with unprovoked VTE will be diagnosed with cancer within 12 months. Although cancer screening has been proposed in these patients, the optimal strategy remains unclear. In a pilot study, we prospectively investigated the use of FDG-PET/CT to screen for occult malignancy in 40 patients with unprovoked VTE.

Materials/Methods

Patients were initially screened for occult malignancy with a focused history, physical, and laboratory evaluation. Patients underwent whole body FDG-PET/CT and were followed for up to two years for a new diagnosis of cancer. The total costs of using FDG-PET/CT as a comprehensive screening strategy were determined using 2010 Medicare reimbursement rates.

Results

Completion of FDG-PET/CT imaging was feasible and identified abnormal findings requiring additional evaluations in 62.5% of patients. Occult malignancy was evident in only one patient (cancer incidence 2.5%) and FDG-PET/CT imaging excluded malignancy in the remainder of patients. No patients with a negative FDG-PET/CT were diagnosed with malignancy during an average (± SD) follow-up of 449 (± 311) days. The use of FDG-PET/CT to screen for occult malignancy added $59,151 in total costs ($1,479 per patient). The majority of these costs were due to the cost of the FDG-PET/CT ($1,162 per patient or 78.5% of total per-patient costs).

Conclusions

FDG-PET/CT may have utility for excluding occult malignancy in patients with unprovoked VTE. The costs of this comprehensive screening strategy were comparable to other screening approaches. Larger studies are needed to further evaluate the utility and cost-effectiveness of FDG-PET/CT as a cancer screening strategy in patients with unprovoked VTE.     

Fish intake and venous thromboembolism: A Danish follow-up study

Introduction

Data on the association between fish intake and venous thromboembolism (VTE) is sparse and inconsistent.

Objective

To investigate whether intake of total, lean or fatty fish is associated with development of incident VTE.

Material and methods

This study is based on the Danish follow-up study Diet, Cancer and Health including 27,178 men and 29,876 women aged 50–64 with no history of cancer. Participants were included between 1993 and 1997 and followed through 2006. Information on fish intake and potential confounders was obtained from baseline questionnaires. The outcome was incident VTE (all) and idiopathic VTE. We used Cox proportional hazard models with age as time axis. Separate analyses were performed for men and women. Adjustment was made for BMI, smoking, physical activity, energy intake and women’s use of hormone replacement therapy.

Results

During follow-up, 641 incident VTE events were verified. We found no association between total fish intake and VTE, but moderate intake of fatty fish was associated with a statistically non-significant 20-40% lower risk of idiopathic VTE compared with consumption of a low intake (less than 8 g) of fatty fish per day.

Conclusions

Intake of neither total nor fatty fish was statistically significantly associated with the incidence rate of VTE. However, intake of fatty fish may be associated with a reduction of the risk of idiopathic VTE.     

Association of blood transfusion and venous thromboembolism after colorectal cancer resection

Introduction

Red blood cell (RBC) transfusion is a common event in the perioperative course of patients undergoing surgery. Transfused blood can disrupt the balance of coagulation factors and modulates the inflammatory cascade. Since inflammation and coagulation are tightly coupled, we postulated that RBC transfusion may be associated with the development of venous thromboembolic phenomena. We queried the American College of Surgeons’ National Surgical Quality Improvement Program (ACS NSQIP) database to examine the relationship between intraoperative blood transfusion and development of venous thromboembolism (VTE) in patients undergoing colorectal resection for cancer.

Materials and Methods

We analyzed the data from 2005 to 2009 for patients undergoing colorectal resections for cancer based on the primary procedure CPT-4 code and operative ICD-9 diagnosis code. The primary outcome was 30-day deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Intraoperative transfusion of RBC's was categorized as: none, 1-2 units, 3-5 units and 6 units or more. DVT/PE occurrences were analyzed by multivariable forward stepwise regression (p for entry < .05, for exit > .10) to identify independent predictors of DVT.

Results

The database contained 21943 colorectal cancer resections. The DVT rate was 1.4% (306/21943) and the PE rate was 0.8% (180/21943). Patients were diagnosed with both only 40 times and the combined DVT or PE rate (VTE) was 2.0% (446/21943). After adjusting for age, gender, race, ASA (American Society of Anesthesiologists) class, emergency procedure, operative duration and complexity of the procedure (based on Relative Value Units, RVU's), along with six clinical risk factors, intraoperative blood transfusion was a significant risk factor for the development of VTE and the risk increased with increasing number of units transfused. Preoperative hematocrit did not enter the multivariable model as an independent predictor of VTE, nor did open versus laparoscopic resection or wound class.

Conclusion

In this study of 21943 patients undergoing colorectal resection for cancer, blood transfusion is associated with increased risk of VTE. Malignancy and surgery are known prothrombotic stimuli, the subset of patients receiving intraoperative RBC transfusion are even more at risk for VTE, emphasizing the need for sensible use of transfusions and rigorous thromboprophylaxis regimens.     

Health care expenditures associated with venous thromboembolism among children

Introduction

We used health insurance claims data from large samples of Medicaid-enrolled and privately insured children to identify children with venous thromboembolism (VTE) and to assess their use of health services and associated expenditures during 2009.

Materials and Methods

Data from the 2009 Thomson Reuters MarketScan® Commercial Database and Multi-State Medicaid database were used to estimate annual expenditures for children 1-17 years of age with VTE. Generalized linear models were used to calculate adjusted annual expenditures for Medicaid-enrolled and privately insured children with VTE, controlling for age, sex, type of health plan, VTE classification (deep vein thrombosis and/or pulmonary embolism), and type of VTE event (idiopathic or secondary) and race (Medicaid only) or region (Commercial only).

Results

During 2009, Medicaid-enrolled and privately insured children with VTE had an average of 1-2 inpatient admissions and 8-10 non-emergency department visits. Unadjusted mean total expenditures were similar for Medicaid-enrolled and privately insured children with VTE, $105,359 and $87,767, respectively. Adjusted mean expenditures for children with secondary VTE were five times higher than for children with idiopathic VTE.

Conclusions

Given the high frequency of secondary VTE in children, most of the associated expenditures may be due to other health conditions. However, children who develop a VTE incur substantial costs of care, even in the absence of related conditions. Additional research is needed to evaluate the long term outcomes for children with VTE including rates of readmission, complications, and the impact of co-morbid conditions.     

Venous thromboembolism among United States soldiers deployed to Southwest Asia

INTRODUCTION: Military operations may represent a high-risk environment for venous thromboembolism (VTE). We sought to identify and describe cases of venous thromboembolism among US military personnel serving in Southwest Asia, and estimate relative disease rates compared to non-deployed personnel. MATERIALS AND METHODS: Retrospective review of imaging archives, hospital discharge codes, case logs and autopsy records for the diagnosis of deep vein thrombosis or pulmonary embolism occurring from 1 March 2003 through 29 February 2004 among U.S. military personnel deployed to Southwest Asia. Rates of disease in deployed and non-deployed active-duty soldiers were estimated using personnel data and deployment experience obtained from automated rosters. RESULTS: Forty cases of venous thromboembolism were identified. The case-fatality rate was 16% (3/19) among those with pulmonary embolism. Antecedent trauma followed by prolonged air evacuation was present in 55% (22/40). Compared to trauma-associated cases, non-trauma cases were more commonly over 40 years old (44% vs. 5%; p<0.05), assigned to a transportation or quartermaster company (56% vs. 14%; p<0.05), or had a history of remote venous thromboembolism (31% vs. 0%; p<0.05). The overall incidence among deployed active-duty soldiers was 22.1/100,000 person-years. Compared to non-deployed active-duty soldiers, the age-adjusted incidence rate ratio was 1.06 (CI(0.95) 0.68-1.67). CONCLUSIONS: VTE rates among deployed soldiers are relatively low compared to the general population, and are comparable to non-deployed soldiers. Fatalities from PE are not uncommon, and vigilance among clinicians remains warranted. Trauma followed by prolonged air evacuation or ground transport during military operations may represent unique interactive risk factors for venous thromboembolism.     

Risk factors for venous thromboembolism in pre-and postmenopausal women

Introduction

Hemostasis in women is affected by changes of estrogen levels. The role of endogenous estrogens on risk of venous thromboembolism (VTE) remains unclear. The aim of this study was to investigate the importance of acquired and genetic risk factors for VTE in pre-and postmenopausal women.

Method

In a nationwide case-control study we included as cases 1470 women, 18 to 64 years of age with a first time VTE. The 1590 controls were randomly selected and matched by age to the cases. Information on risk factors was obtained by interviews and DNA-analyses. We used unconditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs).

Results

The ORs were generally of similar magnitude in pre- and postmenopausal women. The highest risk was for the combination of surgery and cast (adjusted OR 54.12, 95% CI 16.62-176.19) in postmenopausal women. The adjusted OR for use of menopausal hormone therapy was 3.73 (95% CI 1.86-7.50) in premenopausal and 2.22 (95% CI 1.54-3.19) in postmenopausal women. Overweight was linked to an increased risk and exercise to a decreased risk, regardless of menopausal status.

Conclusion

Menopausal status had only minor influence on the risk levels. Acquired transient risk factors conveyed the highest risks for VTE.     

The impact of co-morbid conditions on family history of venous thromboembolism in Whites and Blacks

Introduction

Our objectives were to compare the magnitude of family history as a risk factor for venous thromboembolism (VTE) risk between Blacks and Whites, and to assess the impact of co-morbid conditions on familial risk for VTE.

Materials and methods

We used data from the Genetic Attributes Thrombosis Epidemiology (GATE) study, a matched case-control study which enrolled Blacks and Whites aged 18-70 years in Atlanta, Georgia. A total of 1,094 case patients with a deep vein thrombosis (DVT) or pulmonary embolism (PE) and 1,264 control patients were interviewed about their family history.

Results

Family history of VTE was a statistically significant risk factor for VTE among Blacks (odds ratio (OR) = 2.9, 95% confidence interval (CI) 2.0-4.1; P value < 0.0001) and among Whites (OR = 2.7, 95% CI 1.9-3.7; P value < 0.0001); among Blacks and Whites who were obese or had hypertension; among Blacks who had diabetes mellitus or cancer; as well as among males and females, and across all age categories. Family history of VTE increased the risk of VTE among Blacks with cancer by about 6-fold, whereas among Blacks without cancer the increased risk due to a positive family history was about 3-fold; a 2-fold relative difference. In addition, family history was a risk factor for VTE among case patients with DVT only or with PE only. The effect of family history generally was stronger among those with recurrent episodes of VTE compared with a first episode of VTE. For example, family history of any VTE was a strong risk factor among Black females with recurrent VTE compared with Black females with first VTE (OR = 3.9, 95% CI 2.0-7.5; P value < 0.0001).

Conclusion

Our study indicated that the adjusted attributable fraction for VTE was 16.9% among Blacks vs. 18.3% among Whites, and certain co-morbid conditions could further increase the risk of VTE associated with a positive family history of VTE.     

Prevalence and prevention of venous thromboembolism in patients with acute exacerbations of COPD

BACKGROUND: Little information exists on the prevalence and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients admitted for acute exacerbations of chronic obstructive pulmonary disease (COPD). OBJECTIVE: To review available literature, we performed a Medline search on papers published on this topic between 1966 and 2003. DATA SYNTHESIS: Pulmonary emboli have been frequently found (up to 30% of cases) in autoptic series that included patients who died from acute exacerbation of COPD, while the real incidence of PE during exacerbation has never been prospectively evaluated by large-scale clinical studies. Diagnosis of concomitant PE in these patients is often missed because symptoms of acute exacerbation of COPD may mimic PE, and non-invasive evaluation by pulmonary scintigraphy or CT scan is less specific. Even if not fatal, undetected and untreated PE may lead to long-term morbidity from pulmonary hypertension and predispose to recurrent venous thromboembolism (VTE). DVT of the lower extremities affects about 10% of patients with acute exacerbation of COPD at admission, but the rate is likely to be underestimated. The results of clinical trials conducted on general medical patients, including COPD patients, indicate that unfractionated heparin (UH) and low molecular weight heparin (LMWH) significantly reduce VTE rates. However, subgroup data on COPD patients are generally not available. In a single randomised, controlled trial specifically conducted on COPD patients, nadroparin reduced the rate of DVT from 28% to 15% without affecting mortality. CONCLUSIONS: Despite a substantial lack of consistent data, VTE appears as a major threat to patients admitted for acute exacerbation of COPD, and pharmacologic prophylaxis should be considered in all high risk situations. However, methodologically rigorous studies in this setting are still needed.     

Lipoprotein (a) in patients with spontaneous venous thromboembolism

INTRODUCTION: Elevated lipoprotein (a) (Lp (a)) has been established as a risk factor of coronary heart disease and stroke. Findings concerning the risk of venous thromboembolism (VTE) in adults are contradictory. The aim of our study was to investigate, whether elevated Lp (a) levels are an independent risk factor of spontaneous symptomatic venous thromboembolism (VTE). Our study was further designed to detect differences in risk profiles between thrombosis patients with and without symptomatic PE. MATERIALS AND METHODS: We investigated Lp (a) in 128 patients with spontaneous symptomatic deep vein thrombosis (DVT, group 1), 105 with spontaneous symptomatic pulmonary embolism with or without DVT (PE, group 2) and 122 healthy controls. Lp (a) was measured with an immunoturbidimetric assay (Tina-quant(R), Roche, Grenzach-Wyhlen, Germany) on a Hitachi-Modular system. RESULTS: Lp (a) levels (mg/L) were not significantly different among groups, median levels (25th-75th percentiles) were 170 (51-386) in group 1, 140 (<20-427) in group 2 and 126 (54-331) in controls, respectively. As continuous variable, odds ratios for VTE for a 100 mg/L increase of Lp (a) were 1.1 [95% confidence interval 0.98-1.2] for group 1 versus controls and 1.1 [0.95-1.2] for group 2 versus controls. The prevalence of Lp (a) above 300 mg/L was not significantly different among patients and controls (group 1: 30%, group 2: 32% and controls: 25%, p=0.4, p=0.2, respectively). CONCLUSIONS: In conclusion we found no association between Lp (a) and VTE regardless whether DVT occurred together with PE or not.     

Clinical probability assessment and D-dimer determination in patients with suspected deep vein thrombosis, a prospective multicenter management study

Objectives

To investigate the reliability of a combined strategy of clinical assessment score followed by a local D-dimer test to exclude deep vein thrombosis. For comparison D-dimer was analysed post hoc and batchwise at a coagulation laboratory.

Design

Prospective multicenter management study.

Setting

Seven hospitals in southern Sweden.

Subjects

357 patients with a suspected first episode of deep vein thrombosis (DVT) were prospectively recruited and pre-test probability score (Wells score) was estimated by the emergency physician. If categorized as low pre-test probability, D-dimer was analysed and if negative, DVT was considered to be ruled out. The primary outcome was recurrent venous thromboembolism (VTE) during 3 months of follow up.

Results

Prevalence of DVT was 23.5% (84/357). A low pre-test probability and a negative D-dimer result at inclusion was found in 31% (110/357) of the patients of whom one (0.9%, [95% CI 0.02-4.96]) had a VTE at follow up. Sensitivity, specificity, negative predictive value and negative likelihood ratio for our local D-dimer test in the low probability group were 85.7%, 74.5%, 98.2%, and 0,19 respectively compared to 85.6%, 67,6%, 97.9% and 0,23 using batchwise analysis at a coagulation laboratory.

Conclusion

Pre-test probability score and D-dimer safely rule out DVT in about 30% of outpatients with a suspected first episode of DVT. One out of 110 patients was diagnosed with DVT during follow up. No significant difference in diagnostic performance was seen between local D-dimer test and the post hoc batch analysis with the same reagent in the low probability group.     

Predictors of attempted inferior vena cava filters retrieval in a tertiary care centre

Background

Retrieval rates of optional recovery inferior vena cava (IVC) filters in US hospitals range from 11 - 70%. We conducted a retrospective study in a Canadian tertiary care centre to determine retrieval rates and predictors of filter removal.

Methods

Consecutive patients who had a retrievable IVC filter inserted or removed between January 2007 and December 2010 were identified. Data collected included baseline demographics, indications for filter insertion and removal, documentation of an IVC filter management plan, reasons for non-retrieval, complications, and death.

Results

275 patients with a median age of 60 years were followed in hospital for a median of 17 patient-days (range 1–876). Indications for filter placement were acute or prior VTE with contraindication to anticoagulation (72.4%), high risk of PE (11.3%) and primary prophylaxis (13.8%). Retrieval was attempted in 165 patients (60%) and was successful in 146 patients (53.1%). The most common reason for failed retrieval was filter thrombus. Predictors of attempted retrieval included documentation of filter plan (odds ratio [OR] 16.7; p < 0.001), surgical indication for IVC filter insertion (OR 4.8; p = 0.002), age ≤ 70 years (OR 3.8; p = 0.001), Hematology service involvement (OR 3.0; p = 0.006), and presence of metastatic cancer (OR 0.2; p = 0.001). Thrombotic complications occurred in 48 patients, including 3 patients who died of fatal PE.

Conclusion

Our filter retrieval rate is suboptimal. Improvements in follow-up documentation or a dedicated clinical service may help increase retrieval rates.     

Contribution of multiple thrombophilic and transient risk factors in the development of cerebral venous thrombosis

INTRODUCTION: Cerebral venous thrombosis (CVT), deep vein thrombosis (DVT) and/or pulmonary embolism (PE) have been associated with thrombophilic defects. However, in contrast to DVT or PE, CVT is a rare disease. We performed a study to identify differences in thrombotic risk profile, predisposing to CVT rather than DVT or PE, particularly the contribution of oral contraception and 11 thrombophilic defects. MATERIALS AND METHODS: A single center case-control study (63 CVT cases and 209 controls with DVT or PE) was performed. RESULTS: Of CVT patients, 11% had experienced prior DVT or PE, and none had recurrent CVT at 5 years follow-up. CVT was more frequently observed in females (79% versus 51%, P<0.001). It was more often secondary (75% versus 50%, P<0.001), mainly due to the difference in age between both groups. At presentation of CVT and DVT/PE, oral contraceptives were used by 78% and 74% of non-pregnant fertile women (P=0.8), respectively. Any thrombophilic defect was demonstrated in 88% of CVT and 75% of DVT/PE patients (P=0.22), sex and age matched. Individual and two or more defects were equally distributed among both groups. CONCLUSIONS: We conclude that a majority of CVT and DVT or PE patients show single or multiple thrombophilic defects. At presentation, oral contraceptive intake was observed more frequently in CVT patients. However, no differences were observed in thrombotic risk profile between both groups of comparable age. Hence, additional unknown risk factors should be considered to explain the different sites of thrombosis in these patients.     

Seasonal variation in the occurrence of venous thromboembolism: A report from the Korean Venous Thromboembolism Working Party

There have been conflicting results on seasonal variation in the occurrence of venous thromboembolism (VTE). It also has never been studied in Asian population. To address these issues, we investigated seasonal changes of the incidence of VTE in Korean population using 1,495 patients with VTE between January 2001 and December 2010. VTE occurred most frequently in the winter and least frequently in the summer (χ2 = 11.83, P = 0.008). In the subset analyses, the same trend was shown in the PE ± DVT group, the unprovoked VTE group, and the VTE without malignancy group. The monthly occurrence rate peaked in December and was at its lowest in July (P = 0.004). In conclusion, our study provides evidence that there is an increased risk for VTE in Korean population in the winter season.     

Clustering of venous thrombosis events at the start of tamoxifen therapy in breast cancer: a population-based experience

Introduction

The epidemiology of tamoxifen and venous thromboembolism (VTE) is not well understood, and most data on tamoxifen toxicity are from adjuvant clinical trials. This study examined the relationship between the duration of tamoxifen use in female patients with breast cancer and the risk of VTE in a large population-based setting.

Materials and Methods

Retrospective electronic data extraction on tamoxifen utilization was undertaken among a cohort of 3572 women with breast cancer seen at Marshfield Clinic between January 1, 1994 and June 31, 2009. Observational follow-up extended until February, 2010.

Results

On initial exposure to tamoxifen, women had a clustering of VTE events. Cox proportional hazards regression, adjusting for multiple clinically-important covariates including age, body mass index, cancer stage, and concurrent diabetes, demonstrated that as use of tamoxifen continued in those without earlier VTE events, risk of subsequent VTE gradually increased, albeit at a lower rate (hazard ratio per year of tamoxifen duration = 1.225, P < 0.0001).

Conclusions

In our study population, initiating tamoxifen coincided with an initial clustering of VTE events, with risks due specifically to tamoxifen, increasing during continued exposure. Evidence suggested that the VTE clustering occurred in high risk individuals at initiation of tamoxifen therapy. Careful selection of patients for whom tamoxifen therapy is appropriate based on susceptibility to VTE is thus required prior to initiation of therapy.     

神经外科术后静脉栓塞症发病率及早期诊断

目的对神经外科术后患者静脉栓塞症（深静脉血栓和肺栓塞）发病率及早期诊断进行前瞻性研究。方法37例神经外科术后患者均按照静脉血栓预防指南进行了弹力袜和（或）四肢间隙气动压迫的预防性治疗。在术后平均12d进行血管彩色超声检查,并通过增强CT扫描明确诊断。结果本组研究中下肢深静脉血栓发生率为13．5％,在发生深静脉血栓患者中肺栓塞发生率为60％,所有静脉血栓患者在临床上均没有症状。结论在神经外科术后患者中静脉血栓症的发病率很高,在采用了预防措施后部分患者依然不能避免,早期预防和早期发现对于减少神经外科术后静脉栓塞症非常重要。     

Testing for occult cancer in patients with pulmonary embolism: Results from a screening program and a two-year follow-up survey

Introduction

An association between pulmonary embolism (PE) and a subsequent diagnosis of cancer has been repeatedly reported. Although screening and early detection might play a pivotal part in reducing mortality from cancer, there are currently no definite data to suggest that cancer screening may improve survival rates in patients with PE. We hereby present the results of a screening program and a two-year follow-up survey for detecting occult cancer in this patient population.

Materials and methods

A total of 107 patients with PE were consecutively enrolled. All subjects underwent an initial screening program followed by a two-year follow-up survey. We calculated the sensitivity of our screening program, and identified risk factors associated with occult cancer by means of logistic regression.

Results

The initial screening program yielded positive results in five patients (4.7%), and four additional cases were identified during the 2-year follow-up. The overall sensitivity of our screening program in idiopathic PE was 55.5%. In the entire study cohort, the number necessary for screening was 12.1 (6.1 in idiopathic PE, and 58 in secondary PE). Logistic regression analysis revealed that a shock index ≥ 1 (odds ratio: 5.467; p = 0.007) and idiopathic PE (odds ratio: 12.82; p = 0.03) were independent risk factors for occult cancer in our PE patients.

Conclusions

A simple and noninvasive screening program yields an acceptable sensitivity for detecting occult cancer in idiopathic PE patients. These results highlight the importance of screening for occult cancer in patients diagnosed with PE, especially in idiopathic forms.     

Statins in the prevention of venous thromboembolism: a meta-analysis of observational studies

Introduction

Studies have established a relationship between inflammation and venous thromboembolism (VTE). Though statins modulate inflammation, it is uncertain if they prevent VTE in heterogeneous populations. A recent randomized trial demonstrated that statins prevent VTE in healthy older adults, yet this has not been well established in other groups, including younger individuals and individuals with comorbidities. The objective of this meta-analysis was to estimate the effect of statins on VTE in a heterogeneous group of adults.

Methods

We systematically reviewed the effect of statins in preventing VTE in adult inpatients and outpatients. We systematically searched MEDLINE (1966-Jan 2010), EMBASE (1980-Jan 2010), Google Scholar, Cochrane Library, PapersFirst, ProceedingsFirst, and ISI Web of Science, manually reviewed references, and contacted experts. Observational studies that compared any dose of statin to no statin or placebo, examined inpatients or outpatients, and assessed VTE, pulmonary embolism, and/or deep vein thrombosis were included. Study selection, data abstraction and study quality evaluation (using the Newcastle-Ottawa Scale) were independently conducted in duplicate.

Results

Four cohort studies and four case-control studies met criteria. Comparing statins to control, the odds ratio for VTE was 0.67 (95% confidence interval 0.53, 0.84), and for deep vein thrombosis was 0.53 (95% confidence interval 0.22, 1.29). The association was attenuated in lower-quality studies and studies enrolling older individuals.

Conclusions

Further well-designed trials are needed to evaluate the risks and benefits of statins in preventing VTE in heterogenous populations of adults, identify high-risk subgroups, and analyze cost-effectiveness of statin use for this indication.