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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.

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

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.