Summary Background Post-thrombotic syndrome (PTS) is a common and burdensome complication of deep venous thrombosis (DVT). Previous trials suggesting benefit of elastic compression stockings (ECS) to ...prevent PTS were small, single-centre studies without placebo control. We aimed to assess the efficacy of ECS, compared with placebo stockings, for the prevention of PTS. Methods We did a multicentre randomised placebo-controlled trial of active versus placebo ECS used for 2 years to prevent PTS after a first proximal DVT in centres in Canada and the USA. Patients were randomly assigned to study groups with a web-based randomisation system. Patients presenting with a first symptomatic, proximal DVT were potentially eligible to participate. They were excluded if the use of compression stockings was contraindicated, they had an expected lifespan of less than 6 months, geographical inaccessibility precluded return for follow-up visits, they were unable to apply stockings, or they received thrombolytic therapy for the initial treatment of acute DVT. The primary outcome was PTS diagnosed at 6 months or later using Ginsberg's criteria (leg pain and swelling of ≥1 month duration). We used a modified intention to treat Cox regression analysis, supplemented by a prespecified per-protocol analysis of patients who reported frequent use of their allocated treatment. This study is registered with ClinicalTrials.gov , number NCT00143598 , and Current Controlled Trials, number ISRCTN71334751. Findings From 2004 to 2010, 410 patients were randomly assigned to receive active ECS and 396 placebo ECS. The cumulative incidence of PTS was 14·2% in active ECS versus 12·7% in placebo ECS (hazard ratio adjusted for centre 1·13, 95% CI 0·73–1·76; p=0·58). Results were similar in a prespecified per-protocol analysis of patients who reported frequent use of stockings. Interpretation ECS did not prevent PTS after a first proximal DVT, hence our findings do not support routine wearing of ECS after DVT. Funding Canadian Institutes of Health Research.
Abstract Background and Objectives Rivaroxaban, a new oral anti-Xa agent, has been approved for use without routine monitoring, but the lack of a predictable drug level measurement may hinder the ...management of anticoagulated patients. The aims of the project were to correlate a Anti-Factor Xa assay using commercial calibrators and controls (Riva Activity) with serum drug levels analyzed by HPLC-MS/MS (Riva MS) in patients currently receiving rivaroxaban, and secondly, to correlate the PT/PTT, thrombin generation (CAT assay) and Thromboelastograph (TEG) with the Riva activity and Riva MS. Methods Recruited patients receiving rivaroxaban prospectively had a total of 3 blood samples taken at least 2 hours apart. Plasma was divided for measurement of PT/PTT, Riva activity, rivaroxaban HPCL-MS/MS, and thrombin generation. TEG activity was measured at one random time point for each patient. Correlation and linear regression evaluations were used to compare the different assays. Results The cases were 22 patients on rivaroxaban, age 56 + 12.6, and 10 healthy controls. There was a strong correlation between Riva activity compared to serum Riva MS (r = 0.99). We found a statistically significant correlation between PT/INR compared to serum measurements of Riva MS (r = 0.68) and anti-Xa activity (r = 0.69). The peak (r = -0.50) and lag time (r = 0.57) CAT correlated with Riva MS measurements. There was no correlation between Riva MS and PTT, TEG R, TEG MA, Endogenous Thrombin potential. Conclusion Riva anti-factor Xa activity assay measured with commercial calibrators and controls provides a reliable assessment of rivaroxaban serum levels for patients requiring measurement of anticoagulant activity. Correlation with other coagulation tests is not sufficiently strong to be used clinically.
Abstract
Deep vein thrombosis (DVT) is a prevalent disease. About 20 to 30% of patients with DVT will develop postthrombotic syndrome (PTS) within months after the initial diagnosis of DVT. There is ...no gold standard for diagnosis of PTS, but clinical signs include pitting edema, hyperpigmentation, phlebectatic crown, venous eczema, and varicose veins. Several scoring systems have been developed for diagnostic evaluation. Conservative treatment includes compression therapy, medications, lifestyle modification, and exercise. Compression therapy, the mainstay and most proven noninvasive therapy for patients with PTS, can be prescribed as compression stockings, bandaging, adjustable compression wrap devices, and intermittent pneumatic compression. Medications may be used to both prevent and treat PTS and include anticoagulation, anti-inflammatories, vasoactive drugs, antibiotics, and diuretics. Exercise, weight loss, smoking cessation, and leg elevation are also recommended. Areas of further research include the duration, compliance, and strength of compression stockings in the prevention of PTS after DVT; the use of intermittent compression devices; the optimal medical anticoagulant regimen after endovascular therapy; and the role of newer anticoagulants as anti-inflammatory agents.
For decades, vitamin K antagonists (VKAs) have been the oral treatment of choice for many thromboembolic conditions. The limitations of VKAs include the need for monitoring through blood testing, ...drug interactions, and narrow therapeutic windows. These shortcomings have led to the development of direct oral anticoagulants. These new oral agents act on specific targets in the coagulation cascade (eg, factor Xa, thrombin) and negate some of the shortcomings of VKAs. This article reviews the roles of dabigatran, rivaroxaban, apixaban, and edoxaban in stroke prevention in nonvalvular atrial fibrillation, for prevention of venous thromboembolism after orthopedic surgery, and in the treatment of venous thromboembolism. Direct oral anticoagulants are at least as efficacious and safe as traditional anticoagulation therapy.
Varicose veins (VVs) are associated with lifestyle-limiting symptoms and complications. Patients who fail compression therapy are candidates for more invasive treatments. This study evaluates the ...efficacy and safety of endovenous foam sclerotherapy (EFS) for the treatment of VVs in a US academic center. We reviewed medical records of a consecutive cohort of patients who underwent EFS over a 2-year period. The primary outcome measure was obliteration of VVs. The secondary outcome measures were symptomatic improvement, ulcer healing, recurrence, and adverse events. A total of 166 patients (217 legs) underwent EFS for pain (81%), pruritis (41%), swelling (17%), ulcerations (17%), thrombophlebitis (14%), and varix rupture (3%). Complete (65%) or near-complete (34%) obliteration was achieved in 215 (99%) legs after one injection. Additional injections achieved complete obliteration in 39 of 53 legs. Ninety-three percent (27/29) of active ulcers healed or were decreasing in size. Five ulcers and 11 VVs recurred. Common adverse events included pain and hyperpigmentation. Thrombosis, hematoma, skin necrosis, and neurologic events were rare. In conclusion, EFS appears to be a safe and effective outpatient therapy for the treatment of symptomatic and complicated VVs.
The aim of this study was to determine if galectin-3 levels were different between participants with peripheral artery disease (PAD) and controls, and to describe its relationship with markers of ...early atherosclerosis. Sixty participants were recruited into two groups: a PAD group (n=31), ankle–brachial index (ABI) ⩽0.90 and a normal ABI group (n=29), ABI 1.0–1.4. PAD participants were older (68.6 vs 61.8 years, p=0.037), more commonly men (68% vs 38%, p=0.02), and with more cardiovascular risk factors (p<0.001). Galectin-3 was 22% higher in PAD participants (mean±SD: 17.6±4.7 vs 14.4±4.1 ng/mL, p<0.01). The odds ratio for galectin-3 in PAD to be 1 ng/mL higher than the participants with normal ABI was 1.19, after adjusting by age and gender (p=0.014). High-sensitivity C-reactive protein (hs-CRP) and homeostatic model assessment (HOMA) were positively associated with galectin-3 in the age- and gender-adjusted model, while arterial elasticity and microalbuminuria were not. In conclusion, galectin-3 levels were higher in participants with PAD.
Abstract Purpose Anticoagulant prophylaxis in patients with central venous catheters is controversial. We performed a meta-analysis of randomized controlled trials of anticoagulant prophylaxis in ...patients with central venous catheters. Methods MEDLINE and EMBASE were searched up to May 2006, supplemented by manual searches of conference proceedings and bibliographies. Results Fifteen trials were included. Unfractionated heparin infusion, oral fixed low-dose vitamin K antagonist, and subcutaneous low-molecular-weight heparin were evaluated. For all catheter-associated deep vein thrombosis (symptomatic and asymptomatic combined), the summary relative risks ranged from 0.31 to 0.73 (all achieved statistical significance). For symptomatic deep vein thrombosis, the summary relative risks ranged from 0.28 to 0.72, but did not achieve statistical significance for any individual regimen. Conclusion Anticoagulant prophylaxis is effective for preventing all catheter-associated deep vein thrombosis in patients with central venous catheters. The effectiveness for preventing symptomatic venous thromboembolism, including pulmonary embolism, remains uncertain.
All of the available diagnostic tests for deep venous thrombosis (DVT) have limitations for excluding acute recurrent DVT. Measurement of plasma d-dimer by using an automated quantitative assay may ...be useful as a rapid exclusion test in patients with suspected recurrent DVT.
To test the safety of withholding additional diagnostic testing and heparin treatment in patients who have a negative d-dimer result at presentation (using the automated quantitative assay STA-Liatest D-di), regardless of their symptoms.
Prospective cohort study.
Academic medical center in the United States.
300 consecutive patients with suspected recurrent DVT.
Patients underwent d-dimer testing at presentation. In patients with negative D-dimer results, heparin therapy was withheld, and no further diagnostic testing for DVT was done as part of the initial evaluation. Patients with positive D-dimer results underwent compression ultrasonography.
The primary outcome measure was a diagnosis of new symptomatic venous thromboembolism confirmed by diagnostic testing during the 3-month follow-up period.
Of the 300 study patients, the d-dimer result was negative at presentation in 134 patients (45%; negative cohort) and positive at presentation in 166 patients. Of the 166 patients, compression ultrasonography documented new DVT in 54 patients. Compression ultrasonography findings were normal in 79 patients and were inconclusive in 33 patients. After 3 months of follow-up, 1 of 134 patients in the negative cohort had confirmed venous thromboembolism (0.75% 95% CI, 0.02% to 4.09%). Venous thromboembolism on follow-up could not be definitively excluded in 5 patients with recurrent leg symptoms and in 1 patient who died. If these patients are considered to have venous thromboembolism, the incidence during the 3-month follow-up period would be 6.0% (CI, 2.6% to 11.4%) (8 of 134 patients).
There is no accepted diagnostic reference standard for recurrent DVT. The precision of the estimate of the incidence of venous thromboembolism on follow-up and the generalizability to settings other than an academic health center should be evaluated.
Measurement of plasma d-dimer by using the automated quantitative assay STA-Liatest D-di seems to provide a simple method for excluding acute recurrent DVT in symptomatic patients.
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