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

Abstract 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

Clinical characteristics and management of cancer-associated acute venous thromboembolism: findings from the MASTER Registry.

Background: Clinical characteristics and management of acute deep vein thrombosis and pulmonary embolism (PE) have been reported to be different in patients with and without cancer. The aim of this paper was to provide information on clinical characteristics and management of acute venous thromboembolism in patients with cancer by means of a large prospective registry. Design and Methods: MASTER is a multicenter registry of consecutively recruited patients with symptomatic, objectively confirmed, acute venous thromboembolism. Information about clinical characteristics and management was collected by an electronic data network at the time of the index event. Results: A total of 2119 patients were enrolled, of whom 424 (20%) had cancer. The incidence of bilateral lower limb deep vein thrombosis was significantly higher in patients with cancer than in patients without cancer (8.5% versus 4.6%; p<0.01), as were the rates of iliocaval thombosis (22.6% versus 14%; p<0.001), and upper limb deep vein thrombosis (9.9% versus 4.8%; p<0.001). Major bleeding (3.3% versus 1.1%; p=0.001), in-hospital treatment (73.3% versus 66.6%; p=0.02) and inferior vena cava filter implantation (7.3% versus 4.1%; p=0.005) were significantly more frequent in patients with cancer, in whom oral anticoagulants were less often used (64.2% versus 82%; p<0.0001). Conclusions: The clinical presentation of acute venous thromboembolism is different and often more extensive in cancer patients than in patients free from malignancy. Moreover, the management of the acute phase of venous thromboembolism is more problematic in cancer patients, especially because of a higher rate of major bleeding and the need for implantation of inferior vena cava filters

Statins, fibrates, and venous thromboembolism: a meta-analysis.

Aims The aim is to make a systematic review of the literature to assess the effect of lipid-lowering drugs on venous thromboembolism (VTE) occurrence. Methods and results MEDLINE and EMBASE databases were searched to identify studies that evaluated the effect of lipid-lowering drugs, in particular statins and fibrates, on VTE risk until April 2009. A scoring system was used to divide studies into two quality categories. Odds ratios (ORs) and 95% confidence intervals (CIs) were then calculated and pooled using a fixed and a random-effects model. Statistical heterogeneity was evaluated through the use of I2 statistics. Three randomized controlled trials (RCTs), three cohort, and eight case\u2013control studies were included in our systematic review, for a total of 863 805 patients. Statins use significantly reduced VTE risk [OR, 0.81; 95% CI, 0.66\u20130.99, random-effect model)]. There was a very high heterogeneity among the studies (I2 > 80%). The use of fibrates was associated with a significant increase in the risk of VTE (OR, 1.58; 95% CI, 1.23\u20132.02), without heterogeneity (I2 = 0%). Data on other lipid-lowering drugs were lacking. Conclusion This meta-analysis of available literature suggests that statins may lower the risk of VTE, whereas fibrates may increase this risk. Due to several methodological limitations, this conclusion should be considered with caution, and additional, specifically designed RCTs are warranted

Laboratory testing in patients treated with direct oral anticoagulants: a practical guide for clinicians

Click to hear Dr Baglin's perspective on the role of the laboratory in treatment with new oral anticoagulants SUMMARY: One of the key benefits of the direct oral anticoagulants (DOACs) is that they do not require routine laboratory monitoring. Nevertheless, assessment of DOAC exposure and anticoagulant effects may become useful in various clinical scenarios. The five approved DOACs (apixaban, betrixaban, dabigatran etexilate, edoxaban and rivaroxaban) have different characteristics impacting assay selection and the interpretation of results. This article provides an updated overview on (i) which test to use (and their advantages and limitations), (ii) when to assay DOAC levels, (iii) how to interpret the results relating to bleeding risk, emergency situations and perioperative management, and (iv) what is the impact of DOACs on routine and specialized coagulation assays. Assays for anti-Xa or anti-IIa activity are the preferred methods when quantitative information is useful, although the situations in which to test for DOAC levels are still debated. Different reagent sensitivities and variabilities in laboratory calibrations impact assay results. International calibration standards for all specific tests for each DOAC are needed to reduce the inter-laboratory variability and allow inter-study comparisons. The impact of the DOACs on hemostasis testing may cause false-positive or false-negative results; however, these can be minimized by using specific assays and collecting blood samples at trough concentrations. Finally, prospective clinical trials are needed to validate the safety and efficacy of proposed laboratory thresholds in relation to clinical decisions. We offer recommendations on the tests to use for measuring DOACs and practical guidance on laboratory testing to help patient management and avoid diagnostic errors. ispartof: Journal of Thrombosis and Haemostasis vol:16 issue:2 pages:209-219 ispartof: location:England status: publishe

Extended thromboprophylaxis with betrixaban in acutely ill medical patients

BACKGROUND: Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. METHODS: Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. RESULTS: A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). CONCLUSIONS: Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218.)