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The optimal strength of compression needed to prevent post-thrombotic syndrome (PTS) after a proximal deep vein thrombosis (DVT) is debated. We aimed to assess whether 25 mm Hg elastic compression stockings (ECS) are non-inferior to 35 mm Hg ECS in preventing PTS after a DVT.In this multicentre, double-blind, non-inferiority, randomised controlled trial, we enrolled adults (≥18 years) with a first ipsilateral proximal DVT attending 46 French vascular medicine hospital departments or private practices. Participants were randomly allocated (1:1, stratified by centre, age, and sex; with varying block sizes of two and four) to wear 25 mm Hg or 35 mm Hg ECS for 2 years. The primary outcome was the cumulative rate of PTS 2 years after inclusion, defined by a Villalta scale (≥5). Efficacy was assessed by intention-to-treat and in eligible participants who had complete primary outcome data. A per-protocol analysis was also conducted among compliant patients as a secondary outcome measure. Safety was assessed in all participants who used ECS at least once, and for which we have at least some tolerance information during follow-up. The margin for non-inferiority was 12·5%. This study is registered with ClinicalTrials.gov, NCT01578122, and has been completed.Between June 28, 2012, and July 21, 2017, we enrolled 341 eligible participants who consented to randomisation. 233 (68%) were men and median age was 59 years (IQR 45-70). Collection of ethnicity and race as a routine research variable is not authorised in France. Median follow-up was 735 days (IQR 721-760). 249 (73%) had complete data at 2 years. For the primary analysis, 40 (31%) of 129 participants with complete data in the 25 mm Hg ECS group and 40 (33%) of 120 in the 35 mm Hg group had PTS (absolute difference -2·3% [90% CI -12·1 to 7·4], pAlthough we did not reach the prespecified sample size, our results suggest that 25 mm Hg ECS are non-inferior to 35 mm Hg ECS in preventing PTS. Larger more powerful studies are needed.Laboratoires Innothera, France.

The postthrombotic syndrome (PTS) is chronic venous insufficiency secondary to a prior deep vein thrombosis (DVT). It is the most common complication of venous thromboembolism (VTE) and, while not fatal, it can lead to chronic, unremitting symptoms as well as societal and economic consequences. The cornerstone of PTS treatment lies in its prevention after DVT. Specific PTS preventative measures include the use of elastic compression stockings and pharmacomechanical catheter-directed thrombolysis. However, the efficacy of these treatments has been questioned by large randomized controlled trials (RCTs). So far, anticoagulation, primarily prescribed to prevent DVT extension and recurrence, appears to be the only unquestionably effective treatment for the prevention of PTS. In this literature review we present pathophysiological, biological, radiological, and clinical data supporting the efficacy of anticoagulants to prevent PTS and the possible differential efficacy among available classes of anticoagulants (vitamin K antagonists [VKAs], low molecular weight heparins [LMWHs] and direct oral anticoagulants [DOACs]). Data suggest that LMWHs and DOACs are superior to VKAs, but no head-to-head comparison is available between DOACs and LMWHs. Owing to their potentially greater anti-inflammatory properties, LMWHs could be superior to DOACs. This finding may be of interest particularly in patients with extensive DVT at high risk of moderate to severe PTS, but needs to be confirmed by a dedicated RCT.

The International Consortium for Health Outcomes Measurement assembled an international working group of venous thromboembolism experts and patient representatives to develop a standardised minimum set of outcomes and outcome measurements for integration into clinical practice and potentially research to support clinical decision making and benchmarking of quality of care. 15 core outcomes important to patients and health-care professionals were selected and categorised into four domains: patient-reported outcomes, long term consequences of the disease, disease-specific complications, and treatment-related complications. The outcomes and outcome measures were designed to apply to all patients with venous thromboembolism aged 16 years or older. A measurement tool package was selected for inclusion in the core standard set, with a minimum number of items to be measured at predefined timepoints, which capture all core outcomes. Additional measures can be introduced to the user by a cascade opt-in system that allows for further assessment if required. This set of outcomes and measurement tools will facilitate the implementation of the use of patient-centred outcomes in daily practice.

Contains fulltext : 232751.pdf (Publisher’s version ) (Closed access) Clinical research in venous thromboembolism (VTE) is hindered by variability in the collection and reporting of data and outcomes. A consistent data language facilitates efficiencies, leads to higher quality data, and permits between-study comparisons and evidence synthesis. The International Society on Thrombosis and Haemostasis (ISTH) launched an international task force of more than 50 researchers to develop common data elements for clinical research in venous thromboembolism. The project was organized in seven working groups, each focusing on a topic area: General Core Data Elements; Anticoagulation and Other Therapies; Chronic VTE and Functional Outcomes; Diagnosis of VTE; Malignancy; Perioperative; and Predictors of VTE. The groups met via teleconference to collaboratively identify key data elements and develop definitions and data standards that were structured in a project-specific taxonomy. A Steering Committee met by teleconference and in-person to determine the overall scope of the project and resolve questions arising from the working groups. ISTH held an open public comment period to enable broader stakeholder involvement and feedback. The common data elements were then refined by the working groups to create a set of 512 unique data elements that are publicly available at http://isth.breakthrough.healthcare. The ISTH VTE Common Data Elements are intended to be a living project with ongoing curation, future expansion, and adaptation to meet the needs of the thrombosis and hemostasis research community.

Background International guidelines recommend using the Villalta score (VS) to diagnose the postthrombotic syndrome (PTS). However, a high proportion of PTS detected with VS could just reflect the presence of preexisting primary venous insufficiency (PVI). Furthermore, it is unclear whether the contralateral VS (cl-VS) can be used to assess for preexisting PVI. Objectives To estimate whether cl-VS can be used to assess for preexisting PVI, and to assess the proportion of PTS that could be attributable to preexisting PVI. Methods Subanalysis of the SOX multicenter randomized trial focusing on patients with a first unilateral proximal deep vein thrombosis (DVT) followed for up to 2 years. PVI was defined as a baseline cl-VS > 4, and PTS as VS > 4 in the leg ipsilateral to DVT starting 6 months after DVT. Results Among 680 patients, mean cl-VS remained stable over time: 1.23 (standard deviation [SD] ±2.49) at baseline and 1.17 (±2.20), 1.59 (±2.81), 1.54 (±2.50), 1.65 (±2.82), and 1.55 (±2.63) at the 1-, 6-, 12-, 18-, and 24-month visits, respectively. Baseline cl-VS and ipsilateral VS measured during follow-up were mildly correlated (Pearson correlation = 0.13-0.25). This association disappeared after subtracting the cl-VS measured at the same visit from the ipsilateral VS. Overall, 48.8% of patients developed PTS of whom 12.8% had baseline cl-VS > 4. Conclusion In our study of patients with a first unilateral proximal DVT, the proportion of patients with PTS who had a cl-VS > 4 is modest. However, cl-VS appears to be stable over time. Its assessment could constitute a simple way of documenting preexisting PVI and help to classify patients as having PTS.

Postthrombotic syndrome (PTS) is a burdensome and costly complication of deep vein thrombosis (DVT) that develops in 20%‐40% of patients within 2 years after proximal DVT. In the absence of effective curative treatment, management of PTS relies on its prevention after DVT. The effectiveness of elastic compression stockings (ECS) to prevent PTS is uncertain. We present an overview of published studies assessing the efficacy of ECS to prevent PTS and present the protocol for the CELEST clinical trial. While previous open‐label randomized trials have reported a 50% risk reduction in PTS in patients treated with >30 mm Hg ankle pressure ECS, a large double‐blind trial reported no effect of ECS. We discuss the main potential limitations of these trials, including a placebo effect and suboptimal compliance to ECS. We present the protocol of the CELEST double‐blind randomized trial comparing 2 years of high strength (ankle pressure 35 mm Hg) versus lower strength (ankle pressure 25 mm Hg) ECS in the prevention of PTS after a first acute symptomatic, unilateral, proximal DVT. The use of lower‐strength ECS than that used in previous studies should favor compliance. CELEST may provide important evidence about the efficacy of ECS in the prevention of PTS after DVT. The results will be interpreted in the light of results from recent clinical trials assessing ECS for PTS prevention that reported that the duration of ECS use should be tailored to the individual, if ECS are efficacious in the prevention of PTS.

Introduction Elastic compression stockings (ECSs) are used to treat symptoms of venous insufficiency. However, lack of patient compliance can limit their effectiveness. In a secondary analysis of the SOX Trial, a randomized trial of active vs. placebo ECSs worn for 2 years to prevent postthrombotic syndrome after deep vein thrombosis, we aimed to describe patient‐reported reasons for nondaily use of ECS and to identify predictors of noncompliance during follow‐up. Methods At each follow‐up visit of the SOX Trial, patients were asked how many days per week they wore study stockings, and if not worn daily, to specify the reason(s). Reasons for nondaily use of ECSs were tabulated. Multiple logistic regression modeling was used to identify predictors of stocking noncompliance during follow‐up (defined as use

Purpose of review Management of isolated distal deep vein thrombosis (IDDVT) remains controversial. We summarize recent studies regarding the natural history of IDDVT as well as pertinent therapeutic trials. We also provide our management approach. Recent findings IDDVT is more commonly associated with transient risk factors and less often associated with permanent, unmodifiable risk factors than proximal DVT. IDDVT has a significantly lower risk of proximal extension and recurrence than proximal DVT. Cancer-associated IDDVT has a similar natural history to cancer-associated proximal DVT, with substantially less favourable outcomes than noncancer-associated IDDVT. Anticoagulant treatment reduces the risk of proximal extension and recurrence in IDDVT at the cost of increased bleeding risk. Intermediate dosing of anticoagulation may be effective for treating noncancer-associated IDDVT in patients without prior DVT. Summary IDDVT with a transient risk factor can be treated for 6 weeks in patients without a prior DVT. Unprovoked IDDVT in patients without malignancy can be treated for 3 months. Outpatients without malignancy or a prior DVT can be left untreated and undergo surveillance compression ultrasound in one week to detect proximal extension, but few patients opt for this in practice. Cancer-associated IDDVT should be treated analogously to cancer-associated proximal DVT.

Introduction Postthrombotic syndrome (PTS) is a form of secondary chronic venous insufficiency (CVI) that occurs after deep vein thrombosis (DVT). Effective treatments for PTS are lacking. Micronized purified flavonoid fraction (MPFF) is a venoactive drug used in the treatment of CVI. Objective To determine whether MPFF is a good candidate to explore as a therapeutic agent for PTS. Methods We performed a narrative review in which we identified 14 systematic reviews, 33 randomized controlled trials, and 19 observational studies that discussed the use of MPFF in CVI, as well as studies that reported on the mechanistic action of MPFF in relation to the pathophysiology of PTS. Results MPFF targets a number of pathophysiologic components of PTS. Based on animal models and human studies investigating objective vascular and lymphatic measures, MPFF promotes venous recanalization after DVT, decreases venous remodeling and reflux, inhibits inflammatory processes, improves venous tone and stasis, improves lymphatic circulation, improves capillary hyperpermeability, and decreases tissue hypoxia. Furthermore, MPFF shows promise in improving clinical manifestations, quality of life, and objective venous parameters of CVI. Studies suggest good patient acceptability and tolerability with the use of MPFF in CVI. Conclusion MPFF is a good candidate to explore as a potential therapy for PTS. Confirmatory high‐quality studies are still needed to reinforce the evidence supporting the use of MPFF in CVI. Double‐blind randomized controlled trials with clinical endpoints are needed to assess the clinical efficacy of MPFF in the treatment of PTS.

Background Direct oral anticoagulants (DOACs) are prescribed for over 80% of patients who start anticoagulant therapy for a new diagnosis of atrial fibrillation (AF). Inappropriate DOAC prescriptions are associated with increased mortality. However, limited data exist as to what proportion of primary care physicians (PCPs) initiate anticoagulation in patients with new AF and the extent of their DOAC knowledge. Material and methods We conducted a telephone survey of randomly selected PCPs in Ontario, Canada. Our primary objective was to determine the percentage of PCPs who initiate anticoagulation in new AF patients and the proportion of patients they initiate on DOACs. Our secondary objectives were to assess PCPs' knowledge about DOACs and to identify educational opportunities to address any knowledge gaps. Results Our survey included 50 respondents. After making a new AF diagnosis, 66% of PCPs stated that they usually initiate anticoagulation themselves and 84% prescribed a DOAC at least 75% of the time. Potential DOAC knowledge gaps included: administration considerations, off-label dosing, concomitant use of acetylsalicylic acid (ASA) in stable coronary artery disease (CAD) and use in valvular AF. Conclusion Most PCPs initiate anticoagulants for AF and prescribe DOACs for the vast majority of new patients. PCPs were well versed in certain aspects of DOAC prescribing, however, a number of knowledge gaps were identified. PCPs may benefit from targeted education in these areas to improve patient outcomes in AF.

Isolated distal deep-vein thrombosis (DVT, infra-popliteal DVT without pulmonary embolism) is a common presentation of venous thromboembolism (VTE), but was an exclusion criterion from the pivotal trials that validated the use of direct oral anticoagulants (DOACs) for VTE management. Using data from the international RIETE registry, we analyzed and compared trends in DOACs prescription between January 2011 and June 2019 in patients with distal vs. proximal DVT. We also assessed DOACs' prescriptions and compared the outcomes (VTE recurrence, bleeding and death) of distal DVT patients treated with DOACs vs. those on vitamin K antagonists (VKAs). 2308 patients with distal DVT and 11,364 patients with proximal DVT were included in the current analysis. DOACs were more frequently prescribed in patients with distal than proximal DVT (25% vs. 16%, p < 0.001). DOACs use increased sharply during the observation period (P < 0.001 for trend). In 2018, 56% of patients with distal DVT received DOACs. Distal DVT patients treated with rivaroxaban or edoxaban received the dose recommended for VTE management in most (> 85%) cases. Patients treated with apixaban were older, more likely to have underlying conditions than patients treated with rivaroxaban and, in most cases (> 75%), did not receive the recommended 1-week loading dose for acute VTE management. Outcomes between distal DVT patients treated with VKAs or DOACs appeared to be similar. In patients with distal DVT, DOACs have become the most common anticoagulant regimen. Specific trials are needed to determine the optimal DOACs dose regimen for treatment of distal DVT.

International audience; After a proximal lower limb deep vein thrombosis (DVT; involving popliteal veins or above), up to 40% of patients develop postthrombotic syndrome (PTS) as assessed by the Villalta scale (VS). Poor initial anticoagulant treatment is a known risk factor for PTS. The risk of developing PTS after isolated distal DVT (infra-popliteal DVT without pulmonary embolism), and the impact of anticoagulant treatment on this risk, are uncertain.Methods: Long-term follow-up of CACTUS double-blind trial comparing 6 weeks of s.c. nadroparin (171 IU/kg/d) versus s.c. placebo for a first symptomatic isolated distal DVT. At least 1 year after randomization, patients had a PTS assessment in clinic or by phone using the VS.Results: After a median follow-up of 6 years, PTS was present in 30% (n = 54) of the 178 patients who had a PTS assessment. PTS was moderate or severe in 24% (n = 13) of cases. There was no statistically significant difference in prevalence of PTS in the nadroparin versus placebo groups (29% versus 32%, P = .6), except in patients without evidence of primary chronic venous insufficiency (9% versus 24%, P = .04). Rates of venous thromboembolism recurrence during follow-up in the nadroparin and placebo groups were, respectively, 8% (n = 7) and 14% (n = 13; P = .2).Conclusion: After a first isolated distal DVT, the risk of PTS is substantial but much lower than that reported after proximal DVT. Anticoagulation with nadroparin doesn't provide any clear benefit to prevent PTS, except in patients without preexisting chronic venous insufficiency. Anticoagulation might be associated with a lower risk of venous thromboembolism recurrence.

International audience; Background: Distal deep vein thrombosis (infrapopliteal DVT without proximal DVT or pulmonary embolism [PE]) generally shares the same triggering risks factors as proximal DVT. In women of childbearing age, a frequent triggering risk factor is the use of combined oral contraceptive (COC) pills. However, data on the epidemiology and long-term outcomes of COC-associated distal DVT are lacking.Objectives: To assess the epidemiology and long-term outcomes of COC-associated distal DVT.Methods: Using data from the OPTIMEV (Optimisation de l'Interrogatoire dans l'évaluation du risque thrombo-Embolique Veineux [Optimization of Interrogation in the Assessment of Thromboembolic Venous Risk]) multicenter cohort study of patients with objectively confirmed venous thromboembolism (VTE) enrolled between 2004 and 2006, we assessed in nonpregnant or postpartum women aged ≤ 50 years without cancer or history of VTE (i) proportion of COC-associated distal DVTs among women with distal DVTs and among women with COC-associated VTEs (distal DVT, proximal DVT, or PE) and (ii) 3-year incidence of death, bleeding, and VTE recurrence.Results: COC-associated distal DVTs (n = 54) represented 43.9% of all distal DVTs and 51.9% of COC-associated VTEs. All but one woman with a COC-associated distal DVT received therapeutic anticoagulation for a median of 3 months. At 3-year follow-up, all women with COC-associated distal DVTs were alive, and none had bled during anticoagulant treatment or had experienced a DVT or PE recurrence after stopping anticoagulants. Similar results were found in patients with COC-associated proximal DVT and PE: The VTE recurrence rate was 1.7% per patient-year (PY) and 0% PY, respectively, and there were no deaths or major bleeds in either group.Conclusions: Distal DVT was the most frequent clinical presentation of COC-associated VTE and had similarly favorable long-term outcomes as other COC-associated VTE.

Introduction: Elastic compression stockings (ECS) are commonly used for the prevention of post-thrombotic syndrome (PTS) after deep venous thrombosis (DVT). However, their efficacy is controversial. While two open-label studies reported a 50% risk reduction of PTS in the ECS vs. no-ECS groups, a large double-blind study didn't find any benefit of ECS vs. placebo-ECS to prevent PTS. These opposite results could be explained either by a placebo effect in the open-label studies or to a lack of compliance to study ECS in the double-blind study. Additional data on the impact of compliance on ECS efficacy, obtained in a double-blind way, are therefore needed. Methods: We analyzed data from the French, CELEST, multicentre double-blind trial comparing 25mmHg ECS vs. 35mmHg ECS to prevent PTS at 2 years after a first symptomatic ipsilateral proximal DVT (NCT01578122). All CELEST patients who had complete data for primary outcome (i.e. PTS, defined as a Villalta score ≥5 on the DVT affected leg at the one- or 2-year follow up visit) were included. The objectives of this predefined analysis were to: i) compare the incidences of PTS at 2 years according to compliance to ECS (irrespective of allocated treatment group) during the first 3 months of treatment and during the 2-year follow-up; ii) assess independent predictors of PTS using a stepwise multivariable model including all of the following variables (baseline patients' and DVT characteristics, anticoagulant treatment and compliance to ECS) if they achieved a p value of 0.2 or less in univariate analysis as well as ECS strength allocation group; iii) build an induction tree algorithm to measure the impact in terms of incidence of PTS of each of the independent predictor of PTS. Compliance to ECS was defined as reasonable and optimal if the patient had worn the study ECS more than 50% and more than 80% of the time respectively and had a modified GIRERD score of 0-2. Results: 249 patients were eligible for this analysis. Mean baseline age was 57 years, 70% (n=174) were men, 20% (n=50) were obese, 21% (n=52) had previous VTE event, 7% (n=18) had a baseline Villalta score ≥5 and the most proximal extent of DVT was the iliac vein in 15% (n=37) of cases. In 80% (n=179) of cases patients were treated with anticoagulation for more than 6 months after DVT and a direct oral anticoagulant (DOAC) was used in 69% (n=164) of cases. 32 % (n=80) of patients developed PTS at 2 years. When patients wore study ECS>80% of the time (i.e optimal compliance), incidence of PTS over 2 years was 26.1% (n=31). Incidence of PTS was 25.0% (n=10) and 40.5% (n=34) in those patients who wore ECS 50-80% and Conclusions: In our double bling study assessing 25mmHg vs. 35mmHg ECS to prevent PTS, compliance to ECS was a significant independent predictor of PTS in our multivariable model. Impact of ECS use became apparent when patient used ECS at least 50% of the time without any strong benefit beyond. Wearing study ECS>50% of the time was associated with 2-fold decreased risk of developing PTS, which is consistent with the results from previous 'positive' open-label studies. It suggests that use of ECS influences the risk of developing PTS. Our induction tree algorithm evidences that being compliant with ECS seems particularly beneficial in - non-obese - patients with extensive DVT. Figure 1 Figure 1. Disclosures Verriere: Laboratoires Innothera: Current Employment.

Essentials Clinical significance of cancer-related isolated distal deep vein thrombosis (iDDVT) is unknown. We studied patients with iDDVT, with and without cancer, and proximal DVT with cancer. Cancer-related iDDVT patients have a much poorer prognosis than iDDVT patients without cancer. Cancer-related iDDVT patients have a similar prognosis to cancer-related proximal DVT patients. SummaryBackground Isolated distal deep vein thrombosis (iDDVT) (infra-popliteal DVT without pulmonary embolism [PE]) is a frequent event and, in the absence of cancer, is usually considered to be a minor form of venous thromboembolism (VTE). However, the clinical significance of cancer-related iDDVT is unknown. Methods Using data from the observational, prospective multicenter OPTIMEV cohort, we compared, at 3 years, the incidences of death, VTE recurrence and major bleeding in patients with cancer-related iDDVT with those in cancer patients with isolated proximal DVT (matched 1:1 on age and sex) and patients with iDDVT without cancer (matched 1:2 on age and sex). Results As compared with patients with cancer-related isolated proximal DVT (n = 92), those with cancer-related iDDVT (n = 92) had a similar risk of death (40.8% per patient-year (PY) vs. 38.3% per PY; aHR = 1.0, 95% CI[0.7–1.4]) and of major bleeding (3.8% per PY vs. 3.6% per PY, aCHR = 0.9 [0.3–3.2]) and a higher risk of VTE recurrence (5.4% per PY vs. 11.5% per PY; aCHR = 1.8 [0.7–4.5]). As compared with patients with iDDVT without cancer (n = 184), those with cancer-related iDDVT had a nine times higher risk of death (3.5% per PY vs. 38.3% per PY; aHR = 9.3 [5.5–15.9]), a higher risk of major bleeding (1.8% per PY vs. 3.6% per PY; aCHR = 2.0 [0.6–6.1]) and a higher risk of VTE recurrence (5.0% per PY vs. 11.5% per PY; aCHR = 2.0 [1.0–3.7]). The results remained similar in the subgroup of patients without history of VTE. Conclusion Patients with cancer-related iDDVT seem to have a prognosis that is similar to that of patients with cancer-related isolated proximal DVT and a dramatically poorer prognosis than patients with iDDVT without cancer. This underlines the high clinical significance of cancer-related iDDVT and the need for additional studies.

Background In routine clinical practice, in most countries, patients with pulmonary embolism (PE) are hospitalized for clinical surveillance and to start anticoagulant treatment. Clinical trials and guidelines suggest that patients with stable PE can be safely treated as outpatients. This shift in management may increase general practitioners' (GP) role in PE early management. However, GP opinion regarding PE home treatment has never been assessed. Methods Survey conducted in France among a random sample of 360 GP (564 contacted to reach targeted sample size) working in regions representative of national access to French healthcare system. Main objectives were to assess i) GP’ acceptability to PE home treatment ii) GP’ preferred outpatient pathway. Results 87% of GP were favorable to home treatment of stable PE if the medical report is immediately available when the patient is discharged from ER (100%), in the absence of social and medical facility isolation of the patient (99%) and if the patient (99%) and GP (76%) consented. Outpatient pathways should be collaborative, between GP and a thrombosis specialist, and should include specialized follow-up visits at one week (80%), 3–6 months (80%) and when anticoagulant treatment is stopped (97%). 61% of GP felt that direct oral anticoagulants (DOAC) should facilitate PE home treatment, which should improve patient's quality of life. Conclusion The vast majority of interviewed GP are favorable to home treatment of stable PE if a formal outpatient pathway is established. DOAC are perceived as another key for the success of the development of PE home treatment.

Essentials Management of patients with calf deep vein thrombosis remains controversial. We conducted a post-hoc analysis of a placebo controlled LMWH randomized clinical trial. Pain was assessed using visual analogue scale at inclusion, one and six weeks. There was no difference in pain control between the two arms. SUMMARY: Background The optimal management of distal deep vein thrombosis (DVT) is highly debated. The only available placebo-controlled trial suggested the absence of clear benefit of anticoagulation. Many physicians feel that, beyond preventing thromboembolic complications, anticoagulation with low-molecular-weight heparin (LMWH) has the potential to improve pain control. Objectives To analyze whether LMWHs decrease pain in patients with distal deep vein thrombosis. Patients and methods Two-hundred and fifty-two patients included in a multicenter, placebo-controlled, randomized clinical trial of LMWH in patients with acute distal DVT and who were asked to rate their pain at inclusion and at each medical visit, using a visual analogue pain scale (VAS). Results One hundred and thirty patients were randomized in the therapeutic nadroparin arm and 122 patients were randomized in the placebo arm. Mean VAS values were 4.6 (standard deviation [SD] 2.5) at inclusion, 2.1 (SD 2.0) at 1 week and 0.4 (SD 1.2) at 6 weeks. We calculated the individual variation in VAS between inclusion and 1 week in patients in whom VAS was available at the two study time-points. There was no difference in the mean VAS reduction between patients treated with therapeutic nadroparin (n = 106) and with placebo (n = 109): -2.6 (SD 2.4) vs. -2.3 (SD 2.0) after 1 week and -4.4 (SD 2.8) vs. -4.0 (SD 2.4) after 6 weeks, respectively. The use of compression stockings was associated with a reduction in pain. Conclusion These data suggests that LMWH use does not improve pain control as compared with placebo in patients with acute distal DVT.

In patients with deep-vein thrombosis (DVT) in the lower limbs, venous ulcer is the most debilitating and end-stage clinical expression of the post-thrombotic syndrome (PTS). To date, risk factors for PTS-related ulcer in DVT patients have not been identified.We used the international observational RIETE registry to assess the evolution of PTS signs and symptoms during a 3-year follow-up period and to identify independent predictors of PTS ulcer at 1 year in patients with acute DVT.Among 1,866 eligible patients, cumulative rates of PTS ulcer at 1, 2 and 3 years were 2.7% (n = 50), 4.3% (n = 54) and 7.1% (n = 60), respectively. The proportion of patients with PTS symptoms at 1, 2 or 3 years remained stable (≈40%), while the proportion of patients with PTS signs increased slightly over time (from 49 to 53%). Prior history of venous thromboembolism (VTE) (odds ratio [OR] = 5.5 [2.8–10.9]), diabetes (OR = 2.3 [1.1–4.7]), pre-existing leg varicosities (OR = 3.2 [1.7–6.1]) and male sex (OR = 2.5 [1.3–5.1]) independently increased the risk of PTS ulcer at 1 year. Obesity also increased the risk but failed to reach statistical significance (OR = 1.8 [0.9–3.3]). DVT treatment characteristics (duration or drug) did not influence the risk.Our results evidence that after acute DVT, pre-existing leg varicosities, prior venous thromboembolism, diabetes and male gender independently increased the risk for PTS ulcer. This suggests that clinicians should consider strategies aimed to prevent ulcers in high-risk DVT patients, such as preventing VTE recurrence, use of stockings in those with pre-existing venous insufficiency, careful monitoring of diabetic patients and encouraging weight loss in obese patients.

International audience; BACKGROUND: Cancer patients who develop a deep-vein thrombosis (DVT) or a pulmonary embolism (PE) are at higher risk of death than similar cancer patients who do not develop DVT or PE. The impact of isolated superficial venous thrombosis (SVT) (i.e. without DVT or PE) on the prognosis of cancer patients is unknown. METHODS: Data from the OPTIMEV, multicentre, observational study, to compare at 3 years the incidences of death, DVT-PE recurrence and bleeding of cancer patients with objectively confirmed SVT vs. cancer patients with DVT (matched 1:2 on age, sex, cancer stage) and vs. patients with SVT without cancer (matched 1:3 on age and sex). RESULTS: Cancer patients with SVT (n = 34) had a high risk of death (23.2%patient-year(PY)), that was similar to that of cancer patients with DVT (aHR = 1.0[0.6-1.9]) and higher to that of SVT patients without cancer (aHR = 9.0[3.5-23.1]). Cancer patients with SVT received anticoagulants for a median duration of 45 days and had a high risk of DVT-PE recurrence (6.0%PY), similar to that of cancer patients with DVT (adjusted cause-specific HR (aCHR) = 1.5[0.4-5.8]) and higher to that of SVT patients without cancer (aCHR = 2.9[0.7-11.9]). In our population, venous thrombosis on varicose veins was associated with a lower risk of death (aHR = 0.6[0.3-1.0]) and DVT-PE recurrence (aCHR = 0.6[0.2-1.7]). CONCLUSION: Our results suggest that cancer patients with SVT have a poor prognosis, similar to that of patients with cancer-related DVT. The high rate of DVT-PE recurrence suggests that such patients may need longer duration of anticoagulant treatment.

International audience; INTRODUCTION:Distal deep-vein thromboses (iDDVT) are infra-popliteal DVTs. They are as frequent but less serious than proximal DVT. Their management is debated.METHODS:Clinical practice survey among a random selection of 111 general practitioners (GP) and 56 vascular medicine physicians (VMP) working in Languedoc-Roussillon (France) to assess and compare iDDVTs management by GP and VMP.RESULTS:In case of DVT, GP manage their patients alone in 35% of cases. In case of collaborative management, VMP initiate and stop anticoagulants (>74% of cases) whereas GP monitor anticoagulation (>76% of cases). With iDDVT, there was no difference between GP and VMP in terms of use (94% vs. 92%) and intensity of anticoagulation (full dose: 99%vs.100%). Duration of anticoagulation differed: GP modulated less frequently duration of anticoagulation in presence of a transient risk factor (58% vs. 90%, p

International audience

SummaryAcute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30–40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.

International audience; BACKGROUND:The efficacy and safety of anticoagulant treatment is not established for patients with acute symptomatic deep vein thrombosis (DVT) of the calf. We aimed to assess whether therapeutic anticoagulation is superior to placebo in patients with symptomatic calf DVT.METHODS:In this randomised, double-blind, placebo-controlled trial, we enrolled low-risk outpatients (without active cancer or previous venous thromboembolic disease) with a first acute symptomatic DVT in the calf from 23 university medical centres or community medical clinics in Canada, France, and Switzerland. We randomly assigned (1:1) patients to receive either the low-molecular-weight heparin nadroparin (171 UI/kg, subcutaneously, once a day) or placebo (saline 0·9%, subcutaneously, once a day) for 6 weeks (42 days). Central randomisation was done using a computer-generated randomisation list, stratified by study centre. Random allocation sequences of variable block size were centrally determined by an independent research clinical centre. Study staff, patients, and outcome assessors (central adjudication committee) were masked to group assignment. Numbered boxes of active drug or placebo were provided to pharmacies in identical packaging. All patients were prescribed compression stockings and followed up for 90 days. The primary efficacy outcome was a composite measure of extension of calf DVT to proximal veins, contralateral proximal DVT, and symptomatic pulmonary embolism at day 42 in the modified intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding at day 42. The trial was registered with ClinicalTrials.gov, number NCT00421538.FINDINGS:Between Feb 1, 2008, and Nov 30, 2014, we screened 746 patients, enrolling 259 patients (50% of the prespecified sample size), before the trial steering committee terminated the trial because of expiry of study drug and slow recruitment. The intention-to-treat analysis population comprised 122 patients in the nadroparin group and 130 in the placebo group. There was no significant difference between the groups in the composite primary outcome, which occurred in four patients (3%) in the nadroparin group and in seven (5%) in the placebo group (risk difference -2·1%, 95% CI -7·8 to 3·5; p=0·54). Bleeding occurred in five patients (4%) in the nadroparin group and no patients in the placebo group (risk difference 4·1, 95% CI 0·4 to 9·2; p=0·0255). In the nadroparin group one patient died from metastatic pancreatic cancer and one patient was diagnosed with heparin-induced thrombocytopenia type 2.INTERPRETATION:Nadroparin was not superior to placebo in reducing the risk of proximal extension or venous thromboembolic events in low-risk outpatients with symptomatic calf DVT, but did increase the risk of bleeding. Avoidance of systematic anticoagulation for calf DVT could have a substantial impact on individual patients and from a public health perspective.FUNDING:Swiss National Science Foundation, the Programme Hospitalier de Recherche Clinique in France, and the Canadian Institutes of Health Research.

Essentials Long-term risk of recurrence of isolated superficial vein thrombosis (SVT) is under-studied. We analyzed data from a cohort of first SVT and proximal deep vein thrombosis (DVT) without cancer. The risk of recurrence as DVT or pulmonary embolism is twice lower in SVT patients. However, overall risk of recurrence is similar between SVT and proximal DVT patients. Click to hear Dr Decousus' perspective on superficial vein thrombosis SUMMARY: Background Isolated superficial vein thrombosis (iSVT) (without concomitant deep vein thrombosis [DVT] or pulmonary embolism [PE]) is a frequent event, but available data on long-term outcomes are scarce and retrospective. Therefore, we aimed to determine prospectively the risk and type of venous thromboembolism (VTE) recurrence after iSVT and compare them with those of proximal DVT. Methods Using data from the prospective, multicenter, observational, OPTIMEV study, we assessed, at 3 years and after anticoagulants were stopped, the incidence and the type of VTE recurrence (iSVT/DVT/PE) of patients with a first objectively confirmed iSVT without cancer (n = 285), and compared these with those of patients with a first proximal DVT without cancer (n = 262). Results As compared with proximal DVT patients, iSVT patients had a similar overall incidence of VTE recurrence (5.4% per patient-year [PY] versus 6.5% per PY, adjusted hazard ratio [aHR] 0.9, 95% confidence interval [CI] 0.5-1.6), but iSVT recurred six times more often as iSVT (2.7% versus 0.6%, aHR 5.9, 95% CI 1.3-27.1) and 2.5 times less often as deep-VTE events (2.5% versus 5.9%, aHR 0.4, 95% CI 0.2-0.9). Varicose vein status did not influence the risk or the type of VTE recurrence. Saphenian junction involvement by iSVT was not associated with a higher risk of recurrence (5.2% per PY versus 5.4% per PY), but was associated with recurrence exclusively as deep-VTE events. Conclusion In patients with a first iSVT without cancer, after stopping anticoagulants, the incidence of deep-VTE recurrence is half that of DVT patients, but the overall risk of recurrence is similar. Ssaphenian junction involvement seems to influence the risk of deep-VTE recurrence, whereas varicose vein status has no impact or a low impact on VTE recurrence.

International audience; The post-thrombotic syndrome (PTS) is a frequent, potentially disabling complication of deep vein thrombosis (DVT) that reduces quality of life and is costly. Clinical manifestations include symptoms and signs such as leg pain and heaviness, edema, redness, telangiectasia, new varicose veins, hyperpigmentation, skin thickening and in severe cases, leg ulcers. The best way to prevent PTS is to prevent DVT with pharmacologic or mechanical thromboprophylaxis used in high risk patients and settings. In patients whose DVT is treated with a vitamin K antagonist, subtherapeutic INRs should be avoided. We do not suggest routine use of elastic compression stockings (ECS) after DVT to prevent PTS, but in patients with acute DVT-related leg swelling that is bothersome, a trial of ECS is reasonable. We suggest that selecting patients for catheter-directed thrombolytic techniques be done on a case-by-case basis, with a focus on patients with extensive thrombosis, recent symptoms onset, and low bleeding risk, who are seen at experienced hospital centers. For patients with established PTS, we suggest prescribing 20-30 mm Hg knee-length ECS to be worn daily. If ineffective, a stronger pressure stocking can be tried. We suggest that intermittent compression devices or pneumatic compression sleeve units be tried in patients with moderate-to-severe PTS whose symptoms are inadequately controlled with ECS alone. We suggest that a supervised exercise training program for 6 months or more is reasonable for PTS patients who can tolerate it. We suggest that management of post-thrombotic ulcers should involve a multidisciplinary approach. We briefly discuss upper extremity PTS and PTS in children.

The Sapporo criteria-related definition commonly used for diagnosis of the antiphospholipid syndrome (APS) associates the occurrence of thrombotic and/or obstetrical events with persistently positive antiphospholipid antibodies (aPL-Ab), including lupus anticoagulant (LAC), anticardiolipin IgG (aCL-G) or IgM, and/or anti-b2-glycoprotein I IgG or IgM antibodies. Criteria used to define the purely obstetrical clinical subtype of the APS syndrome include the aPLs listed above plus a fetal loss later than 10-weeks gestation, 3 or more unexplained consecutive embryonic losses before the 10th week gestation, or eclampsia or features of placental insufficiency requiring the preterm birth before 34 weeks of a morphologically normal child. Some investigators have questioned the serological criteria associated with this form of APS and have suggested that the aCL-G, anticardiolipin IgM, and anti-b2-glycoprotein I IgM measurements should be excluded. To determine the effects of the various aPL-Ab subtypes on pregnancy outcome, the investigators prospectively monitored women who had had an unexplained embryonic loss during their first pregnancy and were undergoing their untreated second pregnancy. They selected women who did not have APS; any hormonal abnormalities; or inflammatory, infectious, or malignant diseases; and who had normal parental karyotypes; the pregnancy outcomes of 142 women who tested positive for at least 1 of the 5 classical aPL-Abs were compared with those of 142 control women who were confirmed to be aPL-Abs negative. Compared with the women without aPL-Abs, the aPL-Ab-positive women experienced more clinical complications during their second pregnancy, including pregnancy loss (of which the majority were embryonic losses), preeclampsia, placental abruption, and intrauterine fetal growth restriction. The presence of LAC alone (type IIa aPL-Ab positivity) was associated with the highest risk of recurrent embryonic loss and intrauterine growth restriction. Positive tests for combinations of aPL-Ab (type I aPL-Ab positivity) were associated with the highest risk of late complications, placental abruption, and preeclampsia. A finding of anti-b2-glycoprotein I IgM positivity had no apparent diagnostic clinical relevance. These findings demonstrate that among women with a first unexplained pregnancy loss before the 10th week of gestation, those who are aPL-Abs positive have a higher risk of complications in their next pregnancy, including embryonic loss, preeclampsia, placental abruption, and intrauterine growth restriction, than women who are aPL-Abs negative. These findings suggest that the aPL-Ab LAC, aCL-G or IgM, and anti-b2-glycoprotein I IgG are helpful in identifying patients at increased risk of an adverse outcome, whereas anti-b2-glycoprotein I IgM has questionable diagnostic value.

Summary. Background: The clinical significance of symptomatic isolated distal deep vein thrombosis (DVT) is uncertain. Consequently, this leads to important disparities in its management. Objective: To examine the clinical history of isolated distal DVT and to compare it with that of proximal DVT. Methods: Using data from the international, prospective, RIETE registry on patients with confirmed symptomatic venous thromboembolism (VTE), we compared the risk factors and 3-month outcome in patients with isolated distal DVT vs. proximal DVT. Results: Eleven thousand and eighty-six patients with symptomatic DVT, but without pulmonary embolism, were included between 2001 and 2008; 1921 (17.3%) exhibited isolated distal DVT. Anticoagulant treatment was received by 89.1% (1680/1885) of isolated distal DVT and 91.8% (7911/8613) of proximal DVT patients for the entire follow-up period. Isolated distal DVTs were more associated with transient risk factors (i.e. recent travel, hospitalization, recent surgery), whereas proximal DVTs were more associated with chronic states (i.e. ≥75 years or with active cancer). At 3 months, major bleeding rate was lower in patients with isolated distal DVT (1.0% vs. 2.2%, P

International audience; BACKGROUND: Post-thrombotic syndrome (PTS) is the most frequent complication of deep vein thrombosis (DVT). Its diagnosis is based on clinical characteristics. However, symptoms and signs of PTS are non-specific, and could result from concomitant primary venous insufficiency (PVI) rather than DVT. This could bias evaluation of PTS. METHODS: Using data from the REVERSE multicenter study, we assessed risk factors for PTS in patients with a first unprovoked unilateral proximal DVT 5-7 months earlier who were free of clinically significant PVI (defined as absence of moderate or severe venous ectasia in the contralateral leg). RESULTS: Among the 328 patients considered, the prevalence of PTS was 27.1%. Obesity (odds ratio [OR] 2.6 [95% confidence interval (CI) 1.5-4.7]), mild contralateral venous ectasia (OR 2.2 [95% CI 1.1-4.3]), poor International Normalized Ratio (INR) control (OR per additional 1% of time with INR < 2 during anticoagulant treatment of 1.018 [95% CI 1.003-1.034]) and the presence of residual venous obstruction on ultrasound (OR 2.1 [95% CI 1.1-3.7]) significantly increased the risk for PTS in multivariable analyses. When we restricted our analysis to patients without any signs, even mild, of contralateral venous insufficiency (n = 244), the prevalence of PTS decreased slightly to 24.6%. Only obesity remained an independent predictor of PTS (OR 2.6 [95% CI 1.3-5.0]). Poor INR control and residual venous obstruction also increased the risk, but the results were no longer statistically significant (OR 1.017 [95% CI 0.999-1.035] and OR 1.7 [95% CI 0.9-3.3], respectively). CONCLUSIONS: After a first unprovoked proximal DVT, obese patients and patients with even mild PVI constitute a group at increased risk of developing PTS for whom particular attention should be paid with respect to PTS prevention. Careful monitoring of anticoagulant treatment may prevent PTS.

Gris, Jean-Christophe Bouvier, Sylvie Molinari, Nicolas Galanaud, Jean-Philippe Cochery-Nouvellon, Eva Mercier, Erik Fabbro-Peray, Pascale Balducchi, Jean-Pierre Mares, Pierre Quere, Isabelle Dauzat, Michel; The incidence of thrombosis in the purely obstetric form of antiphospholipid syndrome is uncertain. We performed a 10-year observational study of 1592 nonthrombotic women who had experienced 3 consecutive spontaneous abortions before the 10th week of gestation or 1 fetal death at or beyond the 10th week of gestation. We compared the frequencies of thrombotic events among women positive for antiphospholipid Abs (n = 517), women carrying the F5 6025 or F2 rs1799963 polymorphism (n = 279), and women with negative thrombophilia screening results (n = 796). The annual rates of deep vein thrombosis (1.46%; range, 1.15%-1.82%), pulmonary embolism (0.43%; range, 0.26%-0.66%), superficial vein thrombosis (0.44%; range, 0.28%0.68%), and cerebrovascular events (0.32%; range, 0.18%-0.53%) were significantly higher in aPLAbs women than in the other groups despite low-dose aspirin primary prophylaxis. Women carrying 1 of the 2 polymorphisms did not experience more thrombotic events than women who screened negative for thrombophilia. Lupus anticoagulant was a risk factor for unprovoked proximal and distal deep and superficial vein thrombosis and women in the upper quartile of lupus anticoagulant activity had the highest risk. Despite data suggesting that aPLAbs may induce pregnancy loss through nonthrombotic mechanisms, women with purely obstetric antiphospholipid syndrome are at risk for thrombotic complications

SummarySuperficial venous thrombosis (SVT) prognosis is debated and its management is highly variable. It was the objective of this study to assess predictive risk factors for concurrent deep-vein thrombosis (DVT) at presentation and for three-month adverse outcome. Using data from the prospective multicentre OPTIMEV study, we analysed SVT predictive factors associated with concurrent DVT and three-month adverse outcome. Out of 788 SVT included, 227 (28.8%) exhibited a concurrent DVT at presentation. Age >75years (odds ratio [OR]=2.9 [1.5–5.9]), active cancer (OR=2.6 [1.3–5.2]), inpatient status (OR=2.3 [1.2–4.4]) and SVT on non-varicose veins (OR=1.8 [1.1–2.7]) were significantly and independently associated with an increased risk of concurrent DVT. 39.4% of SVT on non-varicose veins presented a concurrent DVT. However, varicose vein status did not influence the three-month prognosis as rates of death, symptomatic venous thromboembolic (VTE) recurrence and major bleeding were equivalent in both non-varicose and varicose SVTs (1.4% vs. 1.1%; 3.4% vs. 2.8%; 0.7% vs. 0.3%). Only male gender (OR=3.5 [1.1–11.3]) and inpatient status (OR=4.5 [1.3–15.3]) were independent predictive factors for symptomatic VTE recurrence but the number of events was low (n=15, 3.0%). Three-month numbers of deaths (n=6, 1.2%) and of major bleedings (n=2, 0.4%) were even lower, precluding any relevant interpretation. In conclusion, SVT on non-varicose veins and some classical risk factors for DVT were predictive factors for concurrent DVT at presentation. As SVT remains mostly a clinical diagnosis, these data may help selecting patients deserving an ultrasound examination or needing anticoagulation while waiting for diagnostic tests. Larger studies are needed to evaluate predictive factors for adverse outcome.

SummaryThere is a lack of consensus on the value of detecting and treating symptomatic isolated distal deep-vein thrombosis (DVT) of the lower limbs. In our study, we compared the risk factors and outcomes in patients with isolated symptomatic distal DVT with those with proximal symptomatic DVT. We analysed the data of patients with objectively confirmed symptomatic isolated DVT enrolled in the national (France), multicenter, prospective OPTIMEV study.This sub-study outcomes were recurrent venous thromboembolism, major bleeding and death at three months. Among the 6141 patients with suspicion of isolated DVT included between November 2004 and January 2006, DVT was confirmed in 1643 patients (26.8%). Isolated distal DVT was more frequent than proximal DVT (56.8% vs. 43.2%, respectively; p=0.01). Isolated distal DVT was significantly more often associated with transient risk factors (recent surgery, recent plaster immobilisation, recent travel), whereas proximal DVT was significantly more associated with more chronic states (active cancer, congestive heart failure or respiratory insufficiency, age >75 years). Most patients (96.8%) with isolated distal DVT received anticoagulant therapies.There was no difference in the percentage of recurrent venous thromboembolism and major bleeding in patients with proximal DVT and isolated distal DVT. However, the mortality rate was significantly higher (p

Background: Isolated superficial vein thrombosis (iSVT) (i.e. without concurrent deep-vein thrombosis or pulmonary embolism) is a frequent event. Its clinical significance and management are controversial. Data on long-term follow-up are scarce and the impact of anatomical characteristics of iSVT on the risk of venous thromboembolism (VTE) (DVT and/or PE) recurrence has not been assessed. Objective: To determine the impact of anatomical characteristics of iSVT on the long-term risk of VTE recurrence. Methods: Using data from the The OPTIMEV (OPTimisation de l'Interrogatoire dans l'_evaluation du risque throMbo-Embolique Veineux) study, a prospective, observational, multicenter study, we assessed at 3 years in patients recruited for an objectively confirmed iSVT i) cumulative rates of DVT, PE and SVT recurrences using the Kaplan-Meier method; and ii) anatomical predictors of VTE recurrence (SVT involving the sapheno-femoral junction (i.e. ≤3 cm), SVT of the trunk of the great saphenous vein, bilateral SVT, SVT occurring in a varicose vein (i.e. C≥2 according to CEAP classification) using a Cox multivariable model adjusted for age, sex, cancer and personal history of VTE. At baseline, all patients with SVT underwent a complete bilateral swhole leg ultrasound to exclude concurrent DVT and during follow-up, all suspected VTE recurrences were confirmed/ruled out with objective tests. All recurrences were centrally adjudicated by the study's expert committee. Results: Among the 479 recruited patients with iSVT, 12.5% (n=60) had a thrombotic recurrence during the 3 years of follow-up. Cumulative rates of recurrence as a PE, DVT and iSVT were 1.9%, 4.8% and 5.8%, respectively. In multivariate analysis, a thrombus involving the sapheno-femoral junction at baseline independently increased the risk of VTE recurrence (HR=3.34 [1.5-7.2]). Presence of varicose veins also increased the risk but this result did not reach statistical significance (HR=1.8 [0.9 - 3.9], p=0.11). Conclusion: In an unselected population of patients with iSVT, long-term risk of VTE recurrence is substantial. Involvement of the sapheno-femoral junction is a strong independent predictor of VTE during the subsequent 3 years. Our results suggest the need for more aggressive management and follow-up of patients with iSVT exhibiting this anatomical characteristic. Disclosures Galanaud: Daichi: Membership on an entity's Board of Directors or advisory committees, Research Funding; bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Sevestre:bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daichi: Membership on an entity's Board of Directors or advisory committees, Research Funding. Pernod:pfizer: Consultancy; leo: Consultancy; bristol meyers: Consultancy; Daichi: Consultancy; bayer: Consultancy. Brisot:bayer: Membership on an entity's Board of Directors or advisory committees; daichi: Membership on an entity's Board of Directors or advisory committees. Quéré:3-M: Research Funding; thuasne: Research Funding; aspen: Research Funding; daichi: Membership on an entity's Board of Directors or advisory committees; bayer: Membership on an entity's Board of Directors or advisory committees; leo: Membership on an entity's Board of Directors or advisory committees.

Background: Venous ulcer, the most serious consequence of chronic venous insufficiency (CVI), is associated with a high morbidity, impaired quality of life and high costs. To date, risk factors for venous ulcer after acute VTE have not been characterized. Objective: To identify independent predictors of venous ulcer development one year after an acute VTE event. Methods: Using data from the RIETE international registry, we analysed risk factors for venous ulcers in patients with an objectively confirmed symptomatic acute VTE (DVT and/or pulmonary embolism (PE)) and followed up for at least one year. During follow-up, signs and symptoms of CVI, occurrence of a venous ulcer in the leg ipsilateral to DVT or, in the absence of reported DVT, in any leg were reported by local investigators. Independent predictors of venous ulcers were assessed using a stepwise multivariable model. Results: Of the 34,144 patients included in the RIETE registry, 4,305 were recruited in centres participating in long-term (1 to 3 years) follow-up. Of these, 54% (n=2,337) underwent an assessment for CVI. After a mean (SD) follow-up of 383 (+/-575) days, 55% (n=1297) had signs or symptoms of CVI and 2.5% (n=59) had developed a venous ulcer. History of previous VTE (OR=4.4 [2.6 - 7.7], signs of venous insufficiency (i.e. leg varicosities) at time of VTE event (OR=2.3 [1.3 - 4.0]), diabetes (OR=2.0 [1.0 - 3.8]), obesity (OR=1.8 [1.1 - 3.2]) and male sex (OR=2.7 [1.5 - 4.9]) were independent predictors of an increased risk of venous ulcer. Conversely, older age, presence of an objectively confirmed DVT at study enrolment, anticoagulant duration (1 year), anticoagulant type (extended low molecular weight heparin vs. vitamin K antagonist), or presence of vena cava filter had no significant impact on risk of venous ulcer. When restricting our analysis to the 1790 patients with objectively confirmed DVT only, results remained similar in magnitude. Proximal character of DVT was associated with a 30% non-significant increased risk of - unquestionable - post-thrombotic ulcer but the proportion of distal DVT was low in our population (11%). Conclusions: After an acute VTE event, history of VTE, pre-existing signs of CVI, male sex, diabetes and obesity independently influenced the risk of venous ulcer. VTE therapeutic management (neither duration nor drugs) did not appear to modify this risk. Our results suggest that clinicians should consider strategies aimed to prevent ulcers in high risk patients, such as preventing VTE recurrence, use of compression stockings in those with CVI and encouraging weight loss in obese patients. Disclosures Galanaud: bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daichi: Membership on an entity's Board of Directors or advisory committees, Research Funding. Bertoletti:Daichi: Honoraria; bayer: Honoraria; BMS-Pfizer: Consultancy, Honoraria. Monreal:Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; boehringer: Consultancy, Membership on an entity's Board of Directors or advisory committees; daichii: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Introduction: Recent studies have shown lower rates of cancer (2 – 3%) following a single episode of venous thromboembolism (VTE) than previously described. The absence of any proven impact of early diagnosis has revived the debate about systematic screening for cancer in these patients. The aim of this study was to identify whether any sub-groups of patients were at excessive risk of cancer. Methods: Based on available data at baseline and during a 3 years longitudinal follow-up of the OPTIMEV cohort, a French multicenter prospective epidemiological study (N° NCT00670540), we performed a comparative prospective epidemiological study, whose main objective was to reassess the occurrence of cancer after an episode of VTE. We sought to determine whether among the VTE positive (VTE+) patients there was any sub-group of patients at greater risk of cancer and to define classification criteria that would allow them to be identified. Results: Among 1565 VTE+ patients, 2.7% and 4.7% developed cancer during the 1stand 3 years of follow-up respectively. The probability of cancer before 3 years was similar whether the DVT was proximal or distal. In contrast, the probability of cancer before 3 years depended on the number of sites affected by VTE, 4.2 % [3.1 - 5.6] for those who had presented with unilateral DVT without PE, and 8.5% [4.6 - 15.2] for those with bilateral DVT with or without PE. The probability also depended on whether the thrombosis was idiopathic 7.1% [5.1 - 9.9] vsa probability of 4.1% [3.1- 5.5] for those who had non-idiopathic DVT. The probability of cancer was also linked to whether or not the patient was on anticoagulant treatment at the time of VTE recurrence. This was 24.8 % [13.7 - 42.5] for those who had relapsed whilst on anticoagulant treatment, 13.1% [7.4 -22.5 ] for those who have relapsed when not on anticoagulants, compared with 4.0% [3.1 - 5.2] for those who did not relapse (p < 0.01). After adjustment, in VTE+ patients, there was a significantly higher adjusted HR for patients over 50 years of age (HR 11.1 [2.7 - 45.5] (p < 0.01), those with idiopathic VTE (HR 1.8 [1.1-2.8] (p = 0.02), bilateral DVT with or without PE (HR 1.9 [1.01 - 3.7] (p = 0.05), those who had a recurrence during follow-up whilst on anticoagulant treatment (HR 6.5 [3.2 - 13.4] (p For VTE+ patients over 50 (n = 1169), we sought to classify these patients according to their risk of cancer by weighting risk factors according to adjusted HR from the multivariate model. Three points were given for recurrence while on anticoagulants, one point for a recurrence when not on anticoagulant treatment, one point for cases of idiopathic VTE and one point for cases of bilateral DVT. According to the scoring, the probability of developing cancer during follow-up was depicted table 1. Discussion The utility of systematically screening for cancer during an episode of VTE is debatable. The issue of the cost of screening in relation to its benefit in terms of reducing mortality and the problem of the physical and psycho-social consequences caused by such screening are also increasingly questioned. Based on the lower incidence of cancer observed in this prospective cohort, it might be more accurate to focus further studies regarding cancer screening on high risk population. Conclusion: Bilateral DVT, idiopathic but especially recurrent VTE appear to be good criteria for selecting patients over 50 years of age for whom the issue of cancer testing should be posed. Table 1 Class Risk N (% of VTE+ patients) Probability of cancer at 3y Low risk (score 0) 597 (51%) 3.6% [2.4 – 5.6] Intermediate risk (score 1 – 2) 525 (45%) 9.1% [6.8 – 12.2] High risk (score ≥ 3) 47 (4%) 27.3% [15.6 – 45.1] Disclosures Bosson: Sanofi-Aventis: Research Funding.

Background Acute deep venous thrombosis (DVT) is associated with leg pain and discomfort. Elastic compression stockings (ECS) have the potential to improve DVT-related leg pain by reducing the diameter of distended veins, increasing venous blood flow and reducing venous hypertension. To date, however, the effect of ECS on DVT-related leg pain has not been studied. In the SOX Trial, a randomized trial of active ECS vs. placebo ECS to prevent the post-thrombotic syndrome, we measured leg pain intensity at baseline and at several time-points during follow-up. Objective In a secondary, non-prespecified analysis of the SOX Trial, to determine whether active ECS, compared with placebo (sham) stockings, are effective to reduce leg pain associated with acute proximal DVT. Methods We did a multicenter (24 centres in Canada and U.S.) randomized placebo controlled trial of active ECS vs. placebo ECS after a first, symptomatic proximal DVT. Active ECS were knee length, 30-40 mm Hg (Class II) graduated ECS. Placebo ECS were manufactured to appear identical to active ECS but lacked therapeutic compression. Study stockings were worn on the DVT-affected leg daily and continued for up to 2 years. Exclusion criteria were >10 days since DVT diagnosis, not planned to be treated with anticoagulants, known peripheral arterial disease or limb phlegmasia, anticipated lifespan < 6 months, inability of patient or caregiver to apply ECS, thrombolysis to treat DVT, geographically inaccessible for follow-up visits or unable to give informed consent. Leg pain intensity was assessed on a 10-point Visual Analog Scale (0, no pain; 10, worst possible pain) via patient self-report at baseline, 14 days, 1 month and 60 days after randomization. We compared mean pain scores at each time point in the active ECS vs. placebo ECS groups using t-tests. We repeated this analysis, restricted to patients who reported daily stockings use at the 1 month visit (the first visit at which frequency of stocking use was assessed). We conducted pre-specified subgroup analyses by age, sex, and extent of DVT. Results are presented as mean difference (95% confidence interval [CI]) in pain intensity score between groups. All statistical tests were 2-sided and significance was set at P Results 410 patients were randomized to active ECS and 396 to placebo ECS. One and 2 patients, respectively, were found to be ineligible soon after randomization and excluded from the analysis. Mean time from DVT diagnosis to randomization was 4.7 days. Baseline characteristics were similar in the 2 groups (60% male, mean age 55.1 years, highest proximal extent of DVT was iliac or femoral vein in 70% and popliteal vein in 30%, 87% were out-patients). Pain scores diminished over time in both groups. There were no differences between groups in pain scores at any time-point (Table), and no evidence for subgroup interaction by age category, sex or anatomical extent of DVT (not shown). Conclusions In a large randomized placebo-controlled trial in patients with symptomatic proximal DVT, leg pain improved at each follow-up visit to a similar degree in patients randomized to active ECS and placebo ECS, and we did not find evidence for benefit of active ECS to reduce pain associated with acute proximal DVT. As our first follow-up assessment was 14 days after DVT, we were unable to evaluate if active ECS had a beneficial or detrimental effect on pain scores during the first 2 weeks after DVT. Disclosures: No relevant conflicts of interest to declare.

Abstract 630 Background: Cancer constitutes a strong risk factor for proximal deep-vein thrombosis (DVT). After a proximal DVT, the risk of being diagnosed a previously undiagnosed cancer in the following years is high. This has justified a cancer screening in this situation, the optimal modalities of which (extensive vs. limited screening) are currently under evaluation. However, little is known on the risk of subsequent cancer in case of symptomatic isolated distal DVT (e.g. infra-popliteal DVT without PE) and symptomatic isolated superficial vein thrombosis (SVT) (e.g. without concomitant DVT and PE). The value of cancer screening is therefore debated in these situations. Yet, each of those two other clinical expressions of venous thromboembolic disease (VTE) in the lower limbs is at least as frequent as proximal DVT. Objective: As compared with patients with a first episode of symptomatic isolated proximal DVT (e.g. without PE), we aim assessing the risk of subsequent cancer in patients with a first isolated distal DVT or with a first isolated SVT. A secondary objective was to assess the influence of anatomical characteristics of distal DVT and SVT (deep calf DVT vs. muscular DVT and SVT on varicose vein vs. SVT on non-varicose vein) on the risk of subsequent cancer. Methods: We analysed the data from the OPTIMEV prospective, observational, multicenter study of consecutive in and outpatients recruited after an objectively confirmed symptomatic VTE and followed up three years. All VTE events were diagnosed via a standardized bilateral whole leg compression ultrasonographic protocol screening the entire deep and superficial venous networks. Results: 327 patients with a proximal DVT, 536 with a distal DVT, and 329 with an SVT fulfilled our study's inclusion criteria. 2.9% (n=35) of patients were lost to follow-up before 3 years. At 3 years cumulative rates of cancer were similar whatever the kind of VTE considered (Figure 1). Incidence of subsequent cancer was respectively of 3.9% [2.2 – 6.1] in case of proximal DVT, 4.1% (95% CI [2.7 – 6.1]) in case of distal DVT and 3.1% [1.7 – 5.7] in case of isolated SVT. Neither anatomical characteristics of distal DVT (cumulative rates of subsequent cancer 4.2% [2.3 – 7.4] in case of muscular DVT, 3.7% [1.6 – 8.6] in case of deep calf DVT and 4.3% [1.8 – 9.9] in case of combined muscular and deep calf DVT, p=0.98) nor anatomical characteristics of SVT (cumulative rates of subsequent cancer 1.9% [0.5 – 7.2] in case of SVT on non-varicose vein and 3.4% [1.9 – 7.4] in case of SVT on varicose vein, p=0.4) significantly influenced the risk of subsequent cancer. Main strengths/limitations: This is the largest prospective observational cohort of in and out patients with an objectively confirmed isolated SVT or isolated distal DVT, managed in routine practice, and with a long-term follow-up. Our results only apply to first episodes of isolated SVT or distal DVT. As compared with previous reports on the risk of subsequent cancer in case of VTE, our population of DVT/SVT patients was at low risk of cancer a priori. Indeed, we only included first episodes of VTE, most of which were diagnosed and managed in an outpatient setting and/or were associated with a transient risk factor. Therefore the number of newly diagnosed cancer was limited and we may have lacked statistical power for some sub-group analyses. However our rate of subsequent cancer in proximal DVT patients was in the range of that from recent studies and significantly higher than the expected rate of cancer in the French general population of the same age. Conclusion: In patients managed in routine practice without previous history of cancer or VTE, every clinical expression of lower limb VTE (proximal DVT, distal DVT and SVT) is associated with a similar risk of subsequent cancer. Anatomical characteristics of distal DVT and SVT do not seem to have a strong impact on this risk. These results suggest that cancer screening should not be modulated according to the deep-proximal, deep-distal or superficial location of lower limb thrombosis. Cumulative rates of subsequent cancer according to the proximal, distal or superficial location of VTE were estimated with the Kaplan-Meier method and compared with logrank test. Disclosures: No relevant conflicts of interest to declare.

Abstract 3332 Background: Post thrombotic syndrome (PTS) is the most common complication of deep vein thrombosis (DVT). Symptoms and signs assessed by the Villalta PTS scale are non-specific and may have causes other than PTS, especially primary venous insufficiency. This may lead to an overestimate of patients categorized as having PTS. To date, the frequency and predictors of PTS in patients with DVT who are free of primary venous insufficiency have not been evaluated. Methods: Using data from the REVERSE prospective multicentre cohort study, we analyzed the prevalence and risk factors for PTS in patients who had a first, unprovoked, unilateral proximal DVT 5–7 months previously and did not have clinically significant primary venous insufficiency (defined as the absence of moderate or severe venous ectasia in the contralateral leg). At the time of enrolment in the REVERSE study, PTS was evaluated in the DVT-affected leg using the Villalta scale and was considered to be present if Villalta score >4. Independent predictors of PTS were assessed using a multivariable logistic regression model adjusting for age, sex, and use of compression stockings and included all variables achieving a p value ≤ 0.10 in univariate analysis. Results: Between October 2001 and March 2006, 664 patients were enrolled in the REVERSE study after having received a 5–7 month course of anticoagulant therapy. Of these, 452 had DVT with or without concomitant pulmonary embolism (PE) as the index event. Of these, 131 patients were excluded from this sub-study for the following reasons: previous secondary DVT/PE (n=24), presence of moderate or severe venous insufficiency in the contralateral leg (n=54), no PTS assessment (n=53). Among the remaining 321 sub-study patients, 48% (n=155) reported using compression stockings. The overall prevalence of PTS 5–7 months after DVT was 27.4% (n=88). The distribution of PTS severity category was as follows: mild PTS (Villalta score, 5–9) in 80% (n=70) of cases, moderate PTS (Villalta score, 10–14) in 17% (n=15) of cases and severe PTS (Villalta score ≥15 or ipsilateral leg ulcer) in 3.4% (n=3) of cases. In univariate analysis, age, sex, concomitant PE at presentation, thrombophilia (mutation of factor II or V, elevated factor VIII or hyperhomocysteinemia, presence of a lupus anticoagulant) and levels of the inflammatory marker C reactive protein or elevated ddimer before stopping anticoagulant therapy did not influence the risk of developing a PTS at 5–7 months (all p>0.10). Obesity (OR=2.3 [1.3 – 4.0]), household income When restricting our analysis to the 226 patients without any signs, even mild, of contralateral venous insufficiency, the prevalence of PTS decreased slightly to 24.8% (n=56). Only obesity remained an independent predictor of PTS (OR=2.3 [1.2 – 4.4]). Poor INR control, ultrasonographic features described above and household income Conclusions: In a population of patients with a first unprovoked proximal DVT and without significant primary venous insufficiency, obesity and ultrasonographic evidence of DVT sequelae at 5–7 months after DVT independently influenced the risk of PTS. Mild clinical expression of primary venous insufficiency was also found to be a predictor of PTS and could therefore play a role in PTS pathophysiology. Nevertheless, it had a limited impact on the assessment of the overall prevalence of ipsilateral PTS according to the Villalta scale. Disclosures: Crowther: Pfizer: Consultancy, Honoraria; Leo Pharma: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; BI: Honoraria; CSL Behring: Consultancy; Octaphram: Consultancy; Artisan: Consultancy.