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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.

BackgroundExcessive use of CT pulmonary angiography (CTPA) to investigate pulmonary embolism (PE) in the emergency department (ED) contributes to adverse patient outcomes. Non-invasive D-dimer testing, in the context of a clinical algorithm, may help decrease unnecessary imaging but this has not been widely implemented in Canadian EDs.AimTo improve the diagnostic yield of CTPA for PE by 5% (absolute) within 12 months of implementing the YEARS algorithm.Measures and designSingle centre study of all ED patients >18 years investigated for PE with D-dimer and/or CTPA between February 2021 and January 2022. Primary and secondary outcomes were the diagnostic yield of CTPA and frequency of CTPA ordered compared with baseline. Process measures included the percentage of D-dimer tests ordered with CTPA and CTPAs ordered with D-dimers ResultsOver 12 months, 2695 patients were investigated for PE, of which 942 had a CTPA. Compared with baseline, the CTPA yield increased by 2.9% (12.6% vs 15.5%, 95% CI −0.06% to 5.9%) and the proportion of patients that underwent CTPA decreased by 11.4% (46.4% vs 35%, 95% CI −14.1% to −8.8%). The percentage of CTPAs ordered with a D-dimer increased by 26.3% (30.7% vs 57%, 95% CI 22.2% 30.3%) and there were two missed PE (2/2695, 0.07%).ImpactImplementing the YEARS criteria may safely improve the diagnostic yield of CTPAs and reduce the number of CTPAs completed without an associated increase in missed clinically significant PEs. This project provides a model for optimising the use of CTPA in the ED.

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.

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.

Resume Introduction La maladie veineuse thromboembolique (thrombose veineuse profonde et embolie pulmonaire) est une pathologie frequente, grave mais aussi chronique. Lors de precedentes etudes, la plupart des medecins traitants et des medecins vasculaires declaraient participer a l’education therapeutique de leurs patients. Objectif Evaluer, du point de vue du patient, le role et l’implication des medecins traitants et des medecins vasculaires dans l’information delivree au patient lors de la prise en charge d’une thrombose veineuse profonde. Methode Enquete telephonique realisee aupres des patients francais inclus dans l’essai therapeutique CACTUS sur le traitement des thromboses veineuses profondes distales des membres inferieurs. Resultats Cent trois patients ont ete interroges. Quatre-vingt-douze pour cent (n = 95) se declaraient satisfaits de l’information recue, jugee necessaire dans 96 % (n = 99) des cas et 85 % (n = 88) des patients n’ont pas eprouve le besoin de consulter d’autres sources d’information. Les medecins vasculaires auraient consacre plus de temps a l’information des patients et auraient delivre un message plus exhaustif et plus comprehensible. Plus de 75 % des patients ont declare qu’aucun medecin n’avait aborde les problematiques des precautions a prendre sous anticoagulants, des complications a long terme et de la prevention de la recidive de la maladie veineuse thromboembolique. Conclusion Dans l’etude CACTUS, les medecins vasculaires auraient consacre davantage de temps a l’information medicale qui est jugee satisfaisante d’apres les patients. Des themes importants n’auraient pas ete abordes suggerant la necessite d’une protocolisation de l’information au patient.

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.

Background: Isolated distal deep vein thrombosis (IDDVT) is a common form of venous thromboembolism (VTE). Limited data exist about the clinical characteristics, initial treatment, and short-term outcomes of these patients. Methods: Using the data from the RIETE registry (05/2001-02/2019), we identified patients with IDDVT without pulmonary embolism (PE). We determined the clinical presentation, initial treatment, and 30-day and 90-day outcomes. We compared the findings with patients with proximal DVT without PE. Results: We identified 5,359 patients with IDDVT (mean age 61±17 years, 50% women). The most prevalent comorbidities were hypertension (39%), anemia (28%), prior VTE (14%), active cancer (12%), heart failure (6.7%), and diabetes (6.6%). Recent surgery was reported in 16%. Most participants received anticoagulation (99%), most commonly with low-molecular-weight heparin (88%). No patient received thrombolytics and use of vena cava filters was rare (0.4%). At 30 days, 59 patients (1.1% [99% CI, 0.8%-1.5%]) died, including only 3 from PE (0.1% [99% CI, 0.01%-0.2%]), 44 (0.8% [99% CI, 0.5%-1.2%]) had nonfatal VTE recurrence, and 31 (0.6% [99% CI, 0.4%-0.9%]) had major bleeding. At 90 days, 2.9% (99% CI, 2.4%-3.6%) died (no additional death from PE), 1.5% (99% CI, 1.1%-2.0%) had nonfatal VTE recurrence, and 0.9% (99% CI, 0.6%-1.3%) had major bleeding. When compared with 25,420 individuals with proximal DVT without PE, those with IDDVT had lower co-morbidity burden including diabetes, heart failure, and cancer, but were more likely to have had recent surgery (P Conclusions: In a large multinational study, IDDVT occurred in patients with low comorbidity burden. Most patients with IDDVT received anticoagulation. Fatal PE was rare, and patients had a more benign prognosis compared with those with proximal DVT.

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.

Objectifs Le syndrome post-thrombotique (SPT) est une insuffisance veineuse secondaire a une thrombose veineuse profonde (TVP). C’est la complication la plus frequente des TVP et son incidence et sa severite augmentent avec le temps. Cependant, en raison du faible nombre d’etudes avec un suivi a tres long terme (> 10 ans), l’incidence reelle et les facteurs de risque du SPT a tres long terme sont inconnus. L’objectif de l’etude SPOT est d’apporter des elements de reponses a ces questions. Methode L’etude SPOT est le suivi a 12 ans de 1392 patients avec TVP proximale ou distale et/ou EP et 1392 temoins sans maladie veineuse thromboembolique (MTE) inclus dans l’etude Optimev et en vie a 3 ans. Le critere de jugement principal est le score de Villalta en autoquestionnaire suivi d’un entretien avec un attache de recherche clinique. Presentation pour cet abstract des resultats initiaux des 243 premiers dossiers complets recus (presentation des resultats de 600 dossiers complets attendus en seance). Resultats A l’inclusion, la moyenne d’âge etait de 53 ans ± 13 ans et 57 % des patients etaient des femmes. Cent patients etaient des temoins sans MTE a l’inclusion ou lors du suivi, 79 des TVP distales sans EP, 54 des TVP proximales ± EP et 10 des EP sans TVP (exclus de l’analyse). Un score de Villalta ≥ 10 definissant un SPT invalidant etait retrouve chez 22 % des patients (n = 54) dont 21 % (n = 21) des temoins, 16 % (n = 13) des TVP distales sans EP et 33 % (n = 18) des TVP proximales ± EP. La proportion de SPT severe (Villalta ≥ 15) globale, chez les temoins, les TVP distales et proximales etait respectivement de 10 %, 10 %, 7 % et 15 %. Les facteurs de risque associes a un SPT invalidant/insuffisance veineuse etaient l’obesite, une classe CEAP ≥ 1 et la localisation proximale de la TVP a l’inclusion. Conclusion L’incidence a tres long terme des formes invalidantes du SPT est elevee. Les facteurs independants de la TVP comme la CEAP et l’obesite augmentent le risque de SPT/insuffisance veineuse. Les TVP distales ne semblent pas associees a un risque accru de SPT invalidant.

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.

Objectifs Apres une thrombose veineuse profonde (TVP), des bas de compression elastique (CE) sont frequemment prescrits pour prevenir la survenue d’un syndrome post-thrombotique (SPT). Une observance therapeutique defaillante constitue un frein important a l’efficacite de la CE pour prevenir le SPT. L’utilisation d’une CE moins forte que celle utilisee dans les essais cliniques ( Methodologie Essai therapeutique de non-inferiorite randomise en double insu comparant la CE 25 mmHg vs. 35 mmHg pour prevenir le SPT chez les patients presentant un premier episode de TVP aigue proximale des membres inferieurs sans insuffisance veinolymphatique significative preexistante et traites au moins 3 mois par anticoagulant (clinicalTrial.gov : NCT01578122 ). Le critere principal de jugement est l’incidence cumulee de SPT a 2 ans evaluee par le score de Villalta a 1 ou 2 ans. La marge de non-inferiorite pour la difference de taux de SPT entre les groupes a ete fixee a 12,5 %. Une observance optimale etait definie comme un port de la CE 80 % du temps. Cette etude a ete approuvee par les autorites de sante et un comite d’ethique et tous les patients ont signe un formulaire de consentement eclaire (clinicaltrial.gov : NCT01578122 ). Resultats De 2012 a 2017, 350 patients ont ete randomises. L’incidence cumulee de SPT etait de 31 % dans le groupe 25 mmHg et 33,3 % dans le groupe 35 mmHg (difference absolue −2,3 %, (IC 90 % : −12,1 ; 7,4), p = 0,006 pour la non-inferiorite). L’incidence cumulee de SPT moderes a severes etait de 4 % dans le groupe 25 mmHg et de 9,4 % dans le groupe 35 mmHg, p = 0,09. L’observance dans les groupes 25 mmHg et 35 mmHg etait optimale dans 51,4 % et 41,8 % des cas respectivement, p = 0,1. Chez les patients observants optimaux, l’incidence cumulee du SPT dans les groupes 25 mmHg et 35 mmHg etait de 29,4 % et 21,6 % respectivement, p = 0,3. Conclusions La CE 25 mmHg est non-inferieure a la CE 35 mmHg pour prevenir le SPT a 2 ans et l’observance therapeutique est meilleure numeriquement. Il semble exister une relation dose/reponse chez les patients observants optimaux avec une tendance pour une meilleure observance dans le groupe 25 mmHg.

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.

Contexte Il y a un manque de connaissances en ce qui concerne la presentation, la prise en charge et le devenir des patients presentant une maladie thromboembolique veineuse (MTEV). De nombreux sous-groupes cliniquement pertinents (comme les personnes âgees, les hemorragies recentes et les patientes enceintes) ont ete sous-representes dans les essais cliniques. En outre, le design des essais cliniques est interessant dans certains scenarios, comme par exemple ceux presentant une embolie pulmonaire (EP) hemodynamiquement instable. Objectifs Registro Informatizado Enfermedad TromboEmbolica (RIETE) est un grand registre prospectif et international en cours, concu pour repondre a ces besoins non satisfaits en utilisant des donnees representatives de plusieurs centres. Methodes Cree en Espagne en 2001, RIETE comprend actuellement 206 centres repartis dans 28 pays et a recrute plus de 87 000 patients atteints de MTEV. L’objectif principal est d’ameliorer la prise en charge de la MTEV grâce a une meilleure comprehension de la prevention, ainsi que des donnees demographiques, des comorbidites, des schemas de traitement et du devenir des patients atteints de MTEV. Resultats RIETE a contribue a caracteriser le modele de presentation et de devenir de la MTEV, y compris dans les sous-groupes peu etudies mentionnes precedemment, dans plus de 150 articles de recherche. RIETE a recemment etendu ses activites a la collecte de donnees sur le devenir a long terme et a elargi ses criteres d’inclusion pour inclure d’autres formes de thrombose veineuse (telles que la thrombose veineuse cerebrale et la thrombose veineuse splanchnique). La plateforme RIETE est egalement utilisee pour mener des etudes comparatives pragmatiques d’efficacite, notamment des essais randomises. Les prochaines etapes seraient axees sur la collaboration avec d’autres centres dans le monde et sur les efforts visant a assurer la qualite et l’extension du registre. RIETE devrait continuer a fournir des preuves cliniques pour les sous-groupes de MTEV sous-etudies et jouer un role plus important dans la facilitation d’etudes multicentriques (et internationales) pouvant etre utilisees pour evaluer les variations et les disparites des soins, l’amelioration de la qualite et conduire des etudes comparatives d’efficacite. Conclusions RIETE est un vaste registre, en cours, de patients atteints de MTEV et d’autres affections thrombotiques. Ses resultats pourraient etre utiles pour ameliorer notre comprehension de l’epidemiologie, des tendances en matiere de soins et du devenir des patients atteints de maladie thrombotique.

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.

Background There is a lack of knowledge with regards to contemporary presentation, management, and outcomes of patients with venous thromboembolism (VTE). Many clinically important subgroups (including the elderly, those with recent bleeding, and pregnant patients) have been under-represented in clinical trials. Further, design of clinical trials is challenging in some scenarios, such as in those with hemodynamically-unstable pulmonary embolism (PE). Objectives RIETE (Registro Informatizado Enfermedad TromboEmbolica) is a large prospective multinational ongoing registry, designed to address these unmet needs using representative data from multiple centers. Methods Initiated in Spain in 2001, RIETE currently includes 206 centers in 28 countries and has enrolled over 87,000 patients with VTE. The overarching goal is to improve the management of VTE through better understanding of prevention, as well as demographics, co-morbidities, treatment patterns, and outcomes of patients with VTE. Results RIETE has helped characterize the pattern of presentation and outcomes of VTE, including in the aforementioned understudied subgroups, in over 150 research articles. RIETE has recently expanded to collect long-term outcomes data, and has broadened its inclusion criteria to enroll other forms of venous thrombosis (such as cerebral vein thrombosis and splanchnic vein thrombosis). The RIETE platform is also being used to conduct pragmatic comparative effectiveness studies, including randomized trials. Future steps would focus on collaboration with additional centers across the world, and efforts to ensure the quality and expansion of the registry. It is expected that RIETE will continue to provide clinical evidence for understudied subgroups with VTE, and will have more prominent role for facilitation of multicenter (and multinational studies) that could be used for assessment of variations and disparities in care, quality improvement, and conducting comparative effectiveness research. Conclusions RIETE is a large ongoing registry of patients with VTE and other thrombotic conditions. Its results could be helpful for improving our understanding of the epidemiology, patterns of care and outcomes of patients with thrombotic disease.

Objectif En cas de suspicion de thromboses veineuses profondes (TVP), lorsqu’un echo-Doppler complet des membres inferieurs est realise, plus de la moitie des TVP diagnostiquees sont de TVP distales (TVP infra-poplitee). Cependant, malgre leur frequence, ces TVP n’ont fait l’objet que de peu d’attention car elles sont considerees comme benignes et ne sont pas diagnostiquees dans la plupart des pays actifs dans la recherche en thrombose. L’objectif de cette communication est de presenter l’apport du registre RIETE a la connaissance des TVP distales isolees des membres inferieurs (sans extension au reseau veineux profond proximal et sans embolie pulmonaire associee). Materiel Analyse des patients presentant une TVP distale isolee inclus dans le registre RIETE. Resultats A ce jour, un seul article centre sur les TVP distales a ete publie. Pres de 2000 patients avec TVP distales isolees ont ete analyses et compares a plus de 9000 patients avec TVP proximales ce qui constitue de loin la plus grosse etude publiee a ce jour sur les TVP distales. Il a ete mis en evidence que : –d’un point de vue epidemiologique, les TVP distales sont davantage associees a des facteurs de risque transitoires et moins a des facteurs de risque permanents ; elles presentent un meilleur pronostic en termes de mortalite en raison d’une moindre mortalite par cancer ; –d’un point de vue therapeutique, alors que les recommandations de bonnes pratiques internationales ne recommandent pas de traiter systematiquement avec des anticoagulants les TVP distales, dans RIETE, reflet de la pratique clinique quotidienne dans un grand nombre de pays, la quasi-totalite des TVP distales etaient traitees avec des anticoagulants, la plupart du temps pour une duree de 3 mois. En raison de son caractere observationnel pur et des differences de pratique diagnostiques, le registre RIETE ne permet pas d’apprehender le poids reel des TVP distales au sein des TVP ni de comparer le pronostic des TVP distales et proximales en termes de recidives thromboemboliques et de saignement. Conclusion RIETE a permis de fournir des donnees epidemiologiques solides sur les TVP distales. Comme toute etude observationnelle, il ne permet pas d’apporter des reponses definitives du point de vue de la prise en charge therapeutique. Des analyses sont en cours pour etudier les facteurs de mauvais pronostic et le pronostic a long terme de ces thromboses.

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

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.

Introduction En cas de thrombose veineuse profonde des membres inferieurs (TVP) l’efficacite de la compression elastique (CE) pour prevenir le syndrome post thrombotique est desormais debattue en particulier pour la prevention du syndrome post thrombotique (SPT). En revanche, les recommandations suggerent l’application d’une CE a la phase aigue de la TVP pour soulager le patient des symptomes de la TVP. Nous presentons ici les resultats de l’etude Celest (Promoteur Innothera) sur l’evolution a court terme des symptomes de TVP. Materiel et methode Essai therapeutique multicentrique en double aveugle comparant la CE appliquant 25 mmHg a la cheville vs. CE appliquant 35 mmHg a la cheville en cas de premiere TVP proximale des membres inferieurs. Nous avons compare l’evolution des symptomes (douleur et œdeme evalues par le patient sur une echelle analogique de 1–100) au cours des 3 premiers mois. Resultats Les resultats presentes dans ce resume sont des resultats preliminaires avant gel de base et en l’absence de levee d’aveugle. Trois cent cinquante patients ont ete randomises (75 % a l’hopital et 25 % en liberal). Leur âge moyen etait de 57,5 ans, 68 % (n = 238) etaient des hommes. Cinquante-huit pour cent (n = 202) presentaient une TVP du membre inferieur gauche et 15 % une extension iliaque. L’evolution, significative, de la diminution des symptomes a 1 semaine (s1), 1 mois (m1) et 3 mois (m3) etait comparable entre les 2 groupes (NS) : pour la douleur, la mediane etait de 28 avec un interquartile de [10–62] a s1, 13 [8–33] a m1 et 9,5 [4–17] a m3 dans le groupe A et de 19 [9–56] a s1, 12 [7–28] a m1 et 8,5 [4–13] a m3 dans le groupe B ; pour l’œdeme, la mediane etait de 24 [10–57] a s1, 14 [6–35] a m1 et 9 [4–16] a m3 dans le groupe A et 14 [7–53] a s1, 10 [5–19] a m1 et 8 [4–13] a m3 dans le groupe B. Discussion Nos resultats montrent la rapide amelioration sous traitement anticoagulant et compression elastique des symptomes aigus de TVP meme si environ 25 % des patients gardent des symptomes cliniquement significatifs (EVA ≥ 15/100) a trois mois. On n’observe pas de difference statistique selon le type de compression. Conclusion La CE 25 mmHg et la CE 35 mmHg sont similairement efficaces pour traiter la douleur et faire regresser l’œdeme a la phase aigue en cas de TVP proximale des membres inferieurs. Ces donnees suggerent que, compte tenu de la plus grande facilite d’enfilage de la CE 25 mmHg, la CE 25 mmHg peut etre egalement utilisee dans cette indication.

International guidelines recommend extended duration secondary prophylaxis in cancer patients who develop primary venous thromboembolism (VTE). Agent selection is guided in part by one large randomized trial (i.e., CLOT; Lee et al., N Engl J Med 349:146–53, 2003) which demonstrated that dalteparin reduced the relative risk of recurrence by 52% compared with oral vitamin K antagonists (VKA; HR = 0.48, 95% CI, 0.30 to 0.77). In a subgroup analysis from that same trial, patients with renal impairment also derived benefit with dalteparin (VTE rates = 3% vs. 17%; p = 0.011). To measure the economic value of secondary VTE prophylaxis with dalteparin, a patient-level pharmacoeconomic analysis was conducted from the Austrian and French healthcare system perspectives. Chapter 1 Healthcare resource use collected during the CLOT trial was extracted and converted into direct cost estimates. Incremental cost differences between the dalteparin and VKA groups were then combined with health state utilities to measure the cost per quality-adjusted life year (QALY) gained. The dalteparin group had significantly higher costs than the VKA group in both countries (Austria: dalteparin = €2687 vs. VKA = €2012; France: dalteparin = €2053 vs. VKA = €1352: p

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.

Isolated distal deep-vein thrombosis (iDDVT) is a distal deep-vein thrombosis (DVT) without proximal DVT or pulmonary embolism. Although its clinical significance is uncertain, its prevalence is increasing with the use of whole leg compression ultrasonography. Epidemiological data giving reported rates of venous thromboembolism (VTE) are scarce, and there is potential conflict regarding the need to treat with anticoagulant drugs. Therefore, iDDVT management varies widely from one country/physician to another.Data are available from two large multicenter observational studies of iDDVT and proximal DVT without pulmonary embolism (iPDVT), comparing risk factor profiles and early prognosis, and also from clinical trials on iDDVT.iDDVT and iPDVT differ in terms of risk factor profile, iPDVT being more associated with chronic risk factors and iDDVT with transient ones. In the short term, case fatality rates associated with iDDVT suggest that it is a clinically relevant entity and should at least be diagnosed. From a therapeutic point of view, differences in population profile and outcomes between iPDVT and iDDVT, and results from recent clinical trials in favor of a modest VTE potential of iDDVT indicate that specific randomized double-blind trials are necessary to determine an appropriate and accepted mode of care for iDDVT.

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

Objective We studied the relation between Parkinson disease (PD) and professional exposure to pesticides in a community-based case-control study conducted in a population characterized by a high prevalence of exposure. Our objective was to investigate the role of specific pesticide families and to perform dose-effect analyses. Methods PD cases (n = 224) from the Mutualite Sociale Agricole (France) were matched to 557 controls free of PD affiliated with the same health insurance. Pesticide exposure was assessed using a 2-phase procedure, including a case-by-case expert evaluation. Analyses of the relation between PD and professional exposure to pesticides were first performed overall and by broad category (insecticides, fungicides, herbicides). Analyses of 29 pesticide families defined based on a chemical classification were restricted to men. Multiple imputation was used to impute missing values of pesticide families. Data were analyzed using conditional logistic regression, both using a complete-case and an imputed dataset. Results We found a positive association between PD and overall professional pesticide use (odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.1–3.1), with a dose-effect relation for the number of years of use (p = 0.01). In men, insecticides were associated with PD (OR = 2.2, 95% CI = 1.1–4.3), in particular organochlorine insecticides (OR = 2.4, 95% CI = 1.2–5.0). These associations were stronger in men with older onset PD than in those with younger onset PD, and were characterized by a dose-effect relation in the former group. Interpretation Our results support an association between PD and professional pesticide exposure, and show that some pesticides (ie, organochlorine insecticides) may be more particularly involved. Ann Neurol 2009;66:494–504

Objective: To analyse the determinants of anti-haemophilic drug costs in hospitalised patients with haemophilia and to estimate the impact of recombinant activated factor VII (rFVIIa) therapy on this expenditure. Perspective: The perspective of the study was from the viewpoint of the hospital. Design and setting: A prospective study was carried out. All patients with haemophilia who were hospitalised in 1999 in Bicetre public hospital, Paris, France were included in the cohort. Main outcome measures and results: For each of the 96 patients (154 hospital stays), we estimated the costs of anti-haemophilic drugs (coagulation concentrates) used. Costs were then stratified by different variables (severity of the disease, presence of a circulating inhibitor to coagulation factors, etc.) and a multivariate model was developed to determine the relationship between these variables and total anti-haemophilic drug costs, while controlling for potential confounders. Our study revealed: (i) the independent role of the five following variables in contributing to high anti-haemophilic drug expenditure: presence of a circulating inhibitor to coagulation factors, odds ratio (OR) = 16.9 (95% CI: 4.3–66); severity of the disease (factor VIII or factor IX≤0.01 IU/mL), OR = 3.7 (95% CI: 1.6–8.6); length of hospital stay >4 days, OR = 8 (95% CI: 2.2–29.4); age >18 years old, OR = 6.2 (95% CI: 1.6–24.5); and surgical reasons for hospitalisation (whether surgery was haemophilia related [OR = 35.7 (95% CI: 7.3–175)] or not [OR = 5.4 (95% CI: 1.3–22.5)]); (ii) the large share that rFVIIa represented in this expenditure on medicines: rFVIIa was used in 20.1% of hospital stays and accounted for 56.2% of the total anti-haemophilic drug costs, which were estimated at €4 384 732 (2000 values). Conclusions: Our data underline the heavy cost of the treatment of haemophilic patients with an inhibitor to coagulation factors. But, to the question of whether the high expenditure linked to rFVIIa utilisation will be balanced out by later benefits, it is not yet possible to reply with any certainty; further cost-benefit evaluation should be carried out.

Purpose of review Postthrombotic syndrome (PTS) is the most frequent complication of deep vein thrombosis. Its pathophysiology is incompletely understood and therapeutic options are limited. This review aims to present and discuss recently published studies that have improved our knowledge related to PTS. Recent findings From a prognostic point of view, some polymorphisms of plasminogen activator inhibitor-1 and platelet endothelial cell adhesion molecule 1 influence the degree of thrombus resolution after deep vein thrombosis and the subsequent rate of PTS, and could help in predicting the risk of PTS. From a therapeutic point of view, the results of a large multicenter placebo-controlled trial suggest an absence of effectiveness of elastic compression stockings to prevent PTS. In addition, although the Cavent trial of catheter-directed thrombolysis to treat ilio-femoral deep vein thrombosis showed significant reduction in the incidence of PTS that was cost-effective, secondary analyses did not show dramatic improvements in quality of life associated with use of catheter-directed thrombolysis. Summary Choice of anticoagulant to treat deep vein thrombosis may represent a new cornerstone of PTS therapeutic management. Studies are needed to assess the impact of new oral anticoagulants and the benefit of extended courses of low molecular weight heparins on the risk of PTS.

www.thelancet.com Vol 384 July 12, 2014 129 left to the discretion of the observer with no quantitative measurement or use of CEAP (Clinical, Etiological, Anatomical, and Pathophysiological) classification. The results were not reported at 2 years as planned, but rather were a cumulative incidence of post-thrombotic syndrome from 6 to 24 months. There was no diff erence for both endpoints, with 2-year data for the primary outcome available in only 45·5% of patients, and for the secondary endpoint in 27% of patients. This study contradicts previous fi ndings. The design and execution of this trial, including the timing of application of elastic compression stockings, the application itself, and defi nition and evaluation of compliance, seem inappropriate. Patients were randomised at a mean of 4·7 days from the time of deep venous thrombosis, and elastic compression stockings were applied within the first 2 weeks of diagnosis. What was the mean time from diagnosis to elastic compression stockings application? Optimum management in this acute phase is crucial for early symptom relief, recurrence, and late outcome. This has clearly been shown for adequate anticoagulation treatment, but also for compression and immediate mobilisation. Compression and walking exercises reduce pain and swelling immediately, and symptoms diminish after 1 week. The aim of continuing wearing elastic compression stockings is to maintain this effect—this could be crucial because the patient might recognise the immediate benefit from using elastic compression stockings and therefore overall compliance would be improved. Sizing was based on leg measurements and elastic compression stockings were sent to patients without provision of proper training. Most patients are unable to apply stockings without specific instruments or training, especially post-thrombotic syndrome: heparin, a drug discovered a century ago by Jay McLean (in 1916), which revolutionised deep-vein thrombosis prognosis. Moreover, a well-conducted anticoagulation treatment has also been associated with a decreased rate of post-thrombotic syndrome. Therefore, the results of the SOX trial should not be “leaving doctors empty handed”, but should rather reinforce their role in off ering a high-quality anticoagulant treatment to their patients. An ongoing international placebocontrolled trial should assess more precisely the eff ect of heparin on the natural history of post-thrombotic syndrome after a distal deep-vein thrombosis (NCT00539058). The eff ect of new oral anticoagulants on the prevention of post-thrombotic syndrome is another important issue.

Post-thrombotic syndrome (PTS) refers to chronic manifestations of venous insufficiency following a deep-vein thrombosis (DVT). It is a frequent, chronic, burdensome and costly disease for which therapeutic options are limited. Above all, the optimal management of PTS consists of preventing its occurrence: first, by preventing DVT, and second, by preventing development of PTS after a DVT. Prevention of DVT is challenging, particularly in the case of nonsurgical hospital inpatients, where physician’s adherence to recommended thromboprophylaxis is often low. In our opinion, this adherence should be improved by generalizing the use of multi-component approaches, including that of automatic reminders. For prevention of PTS after an acute DVT, our recommendations are as follows. After a proximal (popliteal and above) DVT we recommend early ambulation with daily use of 30–40 mmHg graduated elastic compression stockings (ECS) for two years, in addition to careful monitoring of anticoagulant therapy. Below-knee ECS are preferred to thigh-length ECS, as they have similar efficacy in preventing PTS and are better tolerated. To improve compliance with ECS, patient education is important, and use of lighter strengths of compression in patients not tolerating traditional strengths should be considered. Catheter-directed thrombolysis of acute DVT was recently shown to be effective in preventing PTS, but we believe that confirmatory studies are needed before recommending its general use. The cornerstone of management of established PTS relies on patient education and use of compression therapy. We encourage ambulation, use of ECS to manage symptoms, and participation in an exercise training program, which has the potential to improve patients’ quality of life (QOL) and PTS scores. In the absence of symptom relief, ECS that provide a higher strength (40–50 mmHg) should be tried. In case of moderate to severe PTS, intermittent compressive devices can be used to improve PTS symptoms. Surgery and endovascular procedures, including balloon angioplasty, stent placement, endovenectomy or valve reconstruction should be considered only in specialized centers, and only for patients with severe PTS for whom previous conservative treatment has failed. These techniques are still under evaluation and the level of evidence supporting their use is low.