Idiopathic Venous Thromboembolic Events Research Articles

Prevalence of arterial and venous thromboembolic events in diabetic patients with and without the metabolic syndrome: A cross sectional study

Background Metabolic syndrome (MS) is associated with an increased risk of cardiovascular events. Recent studies have found a higher prevalence of the MS in patients with idiopathic venous thromboembolic events (VTE) compared to controls suggesting a role of the MS in the pathogenesis of VTE. The presence of MS was shown to further increase the risk of arterial cardiovascular diseases (CVD) in diabetic patients. Conversely, there are no studies that have compared the risk of VTE in diabetic patients with and without the MS. Methods A cross sectional study comparing the prevalence of arterial cardiovascular events and VTE in diabetic patients with and without the MS was conducted. Results Nine hundred and fifty three patients were included in the study; 85.7% of patients had MS. Patients with the MS had an increased prevalence of CVD as compared with those without (23.4% vs. 11.8%) and the MS was an independent predictor of CVD in diabetic patients (OR 3.16, 95%CI 1.78, 5.59) after multiple logistic regression analysis. The prevalence of VTE was higher in patients with the MS in comparison to patients without the MS, but this association was not statistically significant (3,43% vs 1.47%; OR 2.38, 95% CI 0.56, 10.10%). Conclusion Our study confirms the role of MS as an adjunctive cardiovascular risk factor in patients with diabetes. There is insufficient evidence to evaluate the role of the as an adjunctive risk factor for VTE in these patients. Further studies are necessary to confirm or refute these preliminary findings.

Seasonal and monthly variability in the incidence of venous thromboembolism

Many studies showed that the occurrence of cardiovascular and cerebrovascular events exhibits a seasonal and monthly variation. Evidences of a seasonal and monthly variation in the incidence of venous thromboembolism (VTE) are more conflicting. We conducted a systematic review and a meta-analysis of the literature to assess the presence of an infradian rhythm of this disease. MEDLINE and EMBASE databases were searched up to January 2010. Monthly and seasonal variation in the incidence of VTE were analysed. We included studies analysing seasonal or monthly aggregation in the incidence of deep-vein thrombosis (DVT) and/or pulmonary embolism (PE) with an objective diagnosis of VTE. Two authors independently reviewed and extracted data. Seventeen studies for a total of about 35,000 patients were included. Twelve studies analysed the seasonal variation and 10 studies the monthly variation of VTE. Our results showed a significantly increased incidence of VTE in winter (chi-square 146.04, p <0.001), with a relative risk (RR) of VTE of 1.143 (99% CI [1.141, 1.144]), and a significantly increased incidence of VTE in January (chi-square 232.57, p <0.001) with an RR of VTE of 1.194 (99% CI 1.186, 1.203). Subgroup analyses including only idiopathic venous thromboembolic events confirmed the results of principal analyses. In conclusion, our data support the presence of an infradian pattern in the incidence of venous thromboembolic events, with a significantly higher risk in Winter and in January. Future studies are needed to better clarify the mechanisms behind this pattern.

Evidence-Based Mini-Review: Should All Patients with Idiopathic Venous Thromboembolic Events Be Screened Extensively for Occult Malignancy?

Introduction A 52-year-old avid tennis player develops an idiopathic left lower extremity deep vein thrombosis. She has no medical problems except for hypertension. She is up to date with her age-specific cancer screening. She had a negative colonoscopy at age 50 and a recent mammogram and Pap smear with no concerning findings. She read that clots may be the first manifestation of cancer and she wonders if she needs an extensive workup to look for a hidden cancer.

Evidence-Based Mini-Review: Should All Patients with Idiopathic Venous Thromboembolic Events Be Screened Extensively for Occult Malignancy?

Evidence-Based Mini-Review: Should All Patients with Idiopathic Venous Thromboembolic Events Be Screened Extensively for Occult Malignancy?

Tumor-Derived Tissue FactorBearing Microparticles Are Associated With Venous Thromboembolic Events in Malignancy

Despite the strong association between malignant disease and thromboembolic disorders, the molecular and cellular basis of this relationship remains uncertain. We evaluated the hypothesis that tumor-derived tissue factor-bearing microparticles in plasma contribute to cancer-associated thrombosis. We developed impedance-based flow cytometry to detect, quantitate, and size microparticles in platelet-poor plasma. We evaluated the number of tissue factor-bearing microparticles in a cohort of cancer patients of different histologies (N = 96) and conducted a case-control study of 30 cancer patients diagnosed with an acute venous thromboembolic event (VTE) compared with 60 cancer patients of similar age, stage, sex, and diagnosis without known VTE, as well as 22 patients with an idiopathic VTE. Tissue factor-bearing microparticles were detected in patients with advanced malignancy, including two thirds of patients with pancreatic carcinoma. Elevated levels of tissue factor-bearing microparticles were associated VTE in cancer patients (adjusted odds ratio, 3.72; 95% confidence interval, 1.18-11.76; P = 0.01). In cancer patients without VTE, a retrospective analysis revealed a 1-year cumulative incidence of VTE of 34.8% in patients with tissue factor-bearing microparticles versus 0% in those without detectable tissue factor-bearing microparticles (Gray test P = 0.002).The median number of tissue factor-bearing microparticles in the cancer VTE cohort (7.1 x 10(4) microparticles/microL) was significantly greater than both the idiopathic VTE and cancer-no VTE groups (P = 0.002 and P = 0.03, respectively). Pancreatectomy in three patients eliminated or nearly eliminated these microparticles which coexpressed the epithelial tumor antigen, MUC-1. We conclude that tumor-derived tissue factor-bearing microparticles are associated with VTE in cancer patients and may be central to the pathogenesis of cancer-associated thrombosis.

Elevated D-dimer levels predict recurrence in patients with idiopathic venous thromboembolism: a meta-analysis.

The evidence on the optimal duration of treatment in patients with an idiopathic venous thromboembolic event (VTE) is inconclusive. d-dimer testing to predict recurrent VTE has been evaluated in several studies. We performed a meta-analysis of studies of patients with idiopathic VTE treated with oral anticoagulation therapy (OAT) to assess the prognostic value of elevated D-dimer levels 1 month after discontinuation of OAT for VTE recurrence. The MEDLINE, EMBASE and Cochrane databases were searched to identify relevant studies. Studies were eligible for inclusion if they included patients with idiopathic VTE and in addition reported results for this group separately, had measured D-dimer approximately 1 month after discontinuation of OAT and had reported on recurrence of VTE. A random-effects model was used to pool study results. Data from four studies (1539 patients) were included in the current analysis. All studies reported on the number of recurrent events in the normal and elevated D-dimer groups. Overall, 125 of 751 patients (16.6%) with elevated D-dimer levels experienced recurrent VTE during the period of follow-up compared with 57 of 788 patients (7.2%) with normal D-dimer levels. Elevated D-dimer levels were significantly associated with recurrent VTE (odds ratio , 2.36; 95% CI, 1.65 to 3.36). Elevated d-dimer levels measured 1 month after discontinuation of OAT identify patients with idiopathic VTE at higher risk of recurrence.

Venous thromboembolic events and organ-specific occult cancers: a review and meta-analysis.

Despite a recognized association between venous thromboembolic events (VTE) and cancer, little is known about the strength and the features of this association. We performed a meta-analysis in order to clarify this issue. We retrieved data from 40 reports published between 1982 and 2007: 12 contained cancer risk estimates for patients with either idiopathic or secondary VTE vs. subjects without VTE and 17 for patients with idiopathic vs. secondary VTE. We also pooled risk estimates from four cohort studies to assess the association between VTE and specific forms of cancer and conducted a proportional incidence study, based on the remaining 28 reports, which did not provide risk estimates. The pooled relative risk (RR) of cancer was 3.2 [95% confidence interval (95% CI) 2.4-4.5] for patients with any form of VTE vs. no VTE, 2.7 (95% CI 1.9-3.9) for patients with idiopathic vs. no VTE and 3.8 (95% CI 2.6-5.4) for patients with idiopathic vs. secondary VTE. In the pooled cohort studies, RRs for VTE vs. no VTE were significantly elevated for cancers of the ovary (RR 7.0), pancreas (RR 6.1), liver (RR 5.6), blood (4.2), brain (RR 3.8), kidney (RR 3.4), lung (3.1), colon (2.9), and esophagus (2.1). In the proportional incidence study, cancers of the pancreas, colon, and blood were significantly more frequently observed than in the general population. Overall we found a 3-fold excess risk of occult cancer in patients with VTE. The risk varies according to tumor site and is highest for cancers of the ovary, pancreas, and liver.

Oral anticoagulation strategies after a first idiopathic venous thromboembolic event

Oral anticoagulation strategies after a first idiopathic venous thromboembolic event

Oral anticoagulation strategies after a first idiopathic venous thromboembolic event

Purpose The optimal duration and intensity of warfarin therapy after a first idiopathic venous thromboembolic event are uncertain. We used decision analysis to evaluate clinical and economic outcomes of different anticoagulation strategies with warfarin. Methods We built a Markov model to assess 6 strategies to treat 40- to 80-year-old men and women after their first idiopathic venous thromboembolic event: 3-month, 6-month, 12-month, 24-month, and unlimited-duration conventional-intensity anticoagulation (International Normalized Ratio, 2–3) and unlimited-duration low-intensity anticoagulation (International Normalized Ratio, 1.5-2). The model incorporated age- and sex-specific clinical parameters, utilities, and costs. Using a societal perspective, we compared strategies based on quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios. Results In our baseline analysis, incremental cost-effectiveness ratios were lower in younger patients and in men, reflecting the higher bleeding risk at older ages, and the lower risk of recurrence among women. Based on a willingness-to-pay of <$50 000/QALY, the 24-month strategy was most cost-effective in 40-year-old men ($48 805/QALY), while the 6-month strategy was preferred in 40-year-old women ($35 977/QALY) and 60-year-old men ($29 878/QALY). In patients aged ≥80 years, 3-month anticoagulation was less costly and more effective than other strategies. Cost-effectiveness results were influenced by the risks associated with recurrent venous thromboembolism, the major bleeding risk of conventional-intensity anticoagulation and the disutility of taking warfarin. Conclusion Longer initial conventional-intensity anticoagulation is cost-effective in younger patients while 3 months of anticoagulation is preferred in elderly patients. Patient age, sex, clinical factors, and patient preferences should be incorporated into medical decision making when selecting an appropriate anticoagulation strategy.

Prevalence of Antiphospholipid Anitbodies in Idiopathic Venous Thromboembolism.

The presence of antiphospholipid antibodies (APLA), which include lupus anticoagulant (LA) and anticardiolipin antibodies (ACA), increases the risk of venous thromboembolism (VTE). Although, the association demonstrated between LA and VTE is strong, that between ACA and VTE is weak with the exception of high titers. This suggestion has been that this may be related to the induction of ACA by acute illness. This may be the explanation for the widely varying frequency of ACA positivity in patients with acute VTE in the current medical literature. The prevalence of LA in patients with acute VTE is more consistent but the value of testing for ACA and LA at presentation of acute VTE remains unknown. We routinely test all idiopathic VTE patients at presentation for LA and ACA. It had been our impression that most positive results revert to normal with subsequent testing. We sough to test this hypothesis. The objective was to determine the prevalence of abnormal LA and ACA results and the frequency of subsequent normalization in patients presenting with a first idiopathic venous thromboembolic event. A retrospective chart review was conducted at the Thrombosis Unit at the Ottawa Hospital. 278 charts of unrelated, consecutive patients with idiopathic VTE were reviewed. 232 patients with single idiopathic venous thromboembolic events with documented LA and ACA results were included. The patients were divided into two groups based on the time between the acute VTE and initial APLA test. The frequency of abnormal LA and ACA on initial and repeat tests was determined in each group. 170 and 177 patients were screened for LA and ACA within one month of the acute VTE. On initial tests, LA and ACA were detected in 14.1% and 7.9% of patients, respectively. However, LA and ACA were present in only 1.2% and 1.7% of patients, respectively, on subsequent tests. In patients screened more than one month after an acute VTE 3.8% of the 52 patients had evidence of LA on initial testing and all were positive on repeat tests. ACA were present in 8% of patients on initial tests and in 6% (75% of the initial positive results) of patients on subsequent tests. A high frequency of positive LA and ACA tests results is observed when these tests are performed at the time of presentation of acute VTE. Repeat testing beyond one month from presentation demonstrates most of the results return to normal suggesting false positive results are common at presentation. However, when the tests are performed one month or longer after the acute VTE, the frequency of positive APLA test is much lower and false positives are uncommon. Screening for APLA should not be performed until at least one month after the diagnosis of idiopathic.

Hypercoagulable state testing and malignancy screening following venous thromboembolic events.

Mounting interest in hypercoagulability, increased availability of hypercoagulable state test 'panels' and enhanced ability to identify abnormalities in tested patients have prompted widespread testing. Testing for acquired and inherited hypercoagulable states uncovers an abnormality in over 50% of patients presenting with an initial venous thromboembolic event (VTE) but may have minimal actual impact on management in most of these patients. Such laboratory screening should be reserved for patients in whom the results of individual tests will significantly impact the choice of anticoagulant agent, intensity of anticoagulant therapy, therapeutic monitoring, family screening, family planning, prognosis determination, and most of all duration of therapy. Testing 'just to know' is neither cost-effective nor clinically appropriate. The most important testing in patients following acute VTE may be age- and gender-specific cancer screening. Cancer screening following VTE seems most prudent in older individuals and in those with idiopathic VTE and no laboratory evidence for an inherited hypercoagulable state. Cancer screening should focus on identification of treatable cancers and those where diagnosis in an early stage favorably impacts patient survival. Extensive searches for occult malignancy employing whole-body computed tomography and serum tumor markers may identify more cancers but without affecting patient outcome. We advocate that physicians should focus their attention more on VTE prophylaxis and proper treatment and less on costly and, at times, invasive testing of questionable value.

Low fibrinogen level: A predisposing factor for venous thromboembolic events with hormone replacement therapy.

Several studies have reported an association between hormone replacement therapy (HRT) in postmenopausal women and increased risk of idiopathic venous thromboembolic events (VTEs). Given the widespread use of HRT, it is important to identify factors that may predispose women on HRT to VTEs. To address this concern, we examined potential risk factors for VTEs in women assigned to HRT in the Postmenopausal Estrogen/Progestin Interventions (PEPI) study, a three-year, double-blinded, placebo-controlled trial of 875 postmenopausal women designed to assess the effects of HRT on heart disease risk factors (HDL cholesterol, fibrinogen, blood pressure, and insulin). Women with a history of estrogen-associated VTEs were excluded from the trial. Ten women, all assigned to HRT, had a VTE during PEPI. Only baseline fibrinogen varied significantly between those who did (mean = 249.0 mg/dl) and did not (mean = 280.8 mg/dl) have a VTE while assigned to HRT (P < 0.03). Adjusting for covariates including age, smoking, body mass index, lipid levels, blood pressure, alcohol, exercise, and prior HRT or oral contraceptive use did not affect this finding. The significantly lower fibrinogen levels seen among women subsequently reporting VTEs may be a marker for a specific, but as yet undefined, coagulopathy that is magnified in the presence of exogenous hormones. However, larger studies are needed to confirm this finding.

Venous thromboembolic disease and combined oral contraceptives: A re-analysis of the MediPlus database.

In October 1995 the Committee on Safety of Medicines advised UK doctors and pharmacists that oral contraceptives containing desogestrel and gestodene were associated with double the risk of venous thromboembolic events (VTE) compared to pills containing other progestogens. In 1997 data was analysed from the MediPlus database of UK general practitioner records, which reported odds ratios for desogestrel and gestodene lower than that for levonorgestrel. Here the results of a more stringent nested case control analysis on the MediPlus database are reported. The study was larger and cases were verified. A crude incidence of idiopathic VTE was found amongst users of combined oral contraceptives of 4.6 per 10 000 exposed women years. Using levonorgestrel 150 microg + ethinyloestradiol 30 microg as reference, non-significant odds ratios of 1.1 (0.5-2.6) for desogestrel 150 microg + ethinyloestradiol 30 microg and 1.1 (0.5-2.4) for gestodene 75 microg + ethinyloestradiol 30 microg were found. The results of this study show no significant difference in risk between different formulations of combined oral contraceptive.