Systems that are used by different organisations to grade the quality of evidence and the strength of recommendations vary. They have different strengths and weaknesses. The GRADE Working Group has developed an approach that addresses key shortcomings in these systems. The aim of this study was to pilot test and further develop the GRADE approach to grading evidence and recommendations.A GRADE evidence profile consists of two tables: a quality assessment and a summary of findings. Twelve evidence profiles were used in this pilot study. Each evidence profile was made based on information available in a systematic review. Seventeen people were given instructions and independently graded the level of evidence and strength of recommendation for each of the 12 evidence profiles. For each example judgements were collected, summarised and discussed in the group with the aim of improving the proposed grading system. Kappas were calculated as a measure of chance-corrected agreement for the quality of evidence for each outcome for each of the twelve evidence profiles. The seventeen judges were also asked about the ease of understanding and the sensibility of the approach. All of the judgements were recorded and disagreements discussed.There was a varied amount of agreement on the quality of evidence for the outcomes relating to each of the twelve questions (kappa coefficients for agreement beyond chance ranged from 0 to 0.82). However, there was fair agreement about the relative importance of each outcome. There was poor agreement about the balance of benefits and harms and recommendations. Most of the disagreements were easily resolved through discussion. In general we found the GRADE approach to be clear, understandable and sensible. Some modifications were made in the approach and it was agreed that more information was needed in the evidence profiles.Judgements about evidence and recommendations are complex. Some subjectivity, especially regarding recommendations, is unavoidable. We believe our system for guiding these complex judgements appropriately balances the need for simplicity with the need for full and transparent consideration of all important issues.

A number of approaches have been used to grade levels of evidence and the strength of recommendations. The use of many different approaches detracts from one of the main reasons for having explicit approaches: to concisely characterise and communicate this information so that it can easily be understood and thereby help people make well-informed decisions. Our objective was to critically appraise six prominent systems for grading levels of evidence and the strength of recommendations as a basis for agreeing on characteristics of a common, sensible approach to grading levels of evidence and the strength of recommendations.Six prominent systems for grading levels of evidence and strength of recommendations were selected and someone familiar with each system prepared a description of each of these. Twelve assessors independently evaluated each system based on twelve criteria to assess the sensibility of the different approaches. Systems used by 51 organisations were compared with these six approaches.There was poor agreement about the sensibility of the six systems. Only one of the systems was suitable for all four types of questions we considered (effectiveness, harm, diagnosis and prognosis). None of the systems was considered usable for all of the target groups we considered (professionals, patients and policy makers). The raters found low reproducibility of judgements made using all six systems. Systems used by 51 organisations that sponsor clinical practice guidelines included a number of minor variations of the six systems that we critically appraised.All of the currently used approaches to grading levels of evidence and the strength of recommendations have important shortcomings.

Deep vein thrombosis (DVT) was thought to be uncommon in Asians and routine thromboprophylaxis in the form of anticoagulation for surgical patients was considered to be unnecessary. The current study aims to provide a contemporary epidemiology of venous thromboembolism in a population-based scale.Information from January 1, 2010 to December 31, 2011 was retrieved from a centralized computer public healthcare database serving mainly an ethnic Han Chinese population of 7.1 million. The incidence, demographics, and hospital mortality rates of DVT and pulmonary embolism (PE) were obtained, and analyzed for different surgical categories.The overall annual incidences of DVT, PE alone, and PE with DVT were 30.0 per 100,000 population, 8.7 per 100,000 population, and 3.0 per 100,000 population, respectively. Overall male to female ratio was 1:1.24. Venous thromboembolic disease was more common with increasing age in both sexes. Thirty days' mortality rates associated with DVT, PE alone, and PE with DVT were 9.0%, 17.4%, and 13.3% respectively. Among the patients who received 103,023 major and intermediate surgical procedures in the study period, the mean incidence of postoperative DVT, PE alone, and PE with DVT were only 0.20% (203.5 patients), 0.08% (85.5 patients), and 0.04% (40.5 patients) respectively.Compared with a similar study 10 years ago, there seemed to be a general increase in incidence of DVT and PE. This study showed that postoperative thromboembolic events were not uncommon, with DVT occurring in up to 0.2% of patients and PE in 0.12% of patients in this longitudinal survey.Copyright © 2016. Published by Elsevier Taiwan.

Venous thromboembolism is a common, potentially avoidable cause of death and morbidity in patients in hospital, including those with stroke. In surgical patients, intermittent pneumatic compression (IPC) reduces the risk of deep vein thrombosis (DVT), but no reliable evidence exists about its effectiveness in patients who have had a stroke. We assessed the effectiveness of IPC to reduce the risk of DVT in patients who have had a stroke.The CLOTS 3 trial is a multicentre parallel group randomised trial assessing IPC in immobile patients (ie, who cannot walk to the toilet without the help of another person) with acute stroke. We enrolled patients from day 0 to day 3 of admission and allocated them via a central randomisation system (ratio 1:1) to receive either IPC or no IPC. A technician who was masked to treatment allocation did a compression duplex ultrasound (CDU) of both legs at 7-10 days and, wherever practical, at 25-30 days after enrolment. Caregivers and patients were not masked to treatment assignment. Patients were followed up for 6 months to determine survival and later symptomatic venous thromboembolism. The primary outcome was a DVT in the proximal veins detected on a screening CDU or any symptomatic DVT in the proximal veins, confirmed on imaging, within 30 days of randomisation. Patients were analysed according to their treatment allocation.ISRCTN93529999.Between Dec 8, 2008, and Sept 6, 2012, 2876 patients were enrolled in 94 centres in the UK. The included patients were broadly representative of immobile stroke patients admitted to hospital and had a median age of 76 years (IQR 67-84). The primary outcome occurred in 122 (8·5%) of 1438 patients allocated IPC and 174 (12·1%) of 1438 patients allocated no IPC; an absolute reduction in risk of 3·6% (95% CI 1·4-5·8). Excluding the 323 patients who died before any primary outcome and 41 without any screening CDU, the adjusted OR for the comparison of 122 of 1267 patients vs 174 of 1245 patients was 0·65 (95% CI 0·51-0·84; p=0·001). Deaths in the treatment period occurred in 156 (11%) patients allocated IPC and 189 (13%) patients allocated no IPC died within the 30 days of treatment period (p=0·057); skin breaks on the legs were reported in 44 (3%) patients allocated IPC and in 20 (1%) patients allocated no IPC (p=0·002); falls with injury were reported in 33 (2%) patients in the IPC group and in 24 (2%) patients in the no-IPC group (p=0·221).IPC is an effective method of reducing the risk of DVT and possibly improving survival in a wide variety of patients who are immobile after stroke.National Institute of Health Research (NIHR) Health Technology Assessment (HTA) programme, UK; Chief Scientist Office of Scottish Government; Covidien (MA, USA).Copyright © 2013 The Authors. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd. All rights reserved.

Despite extensive literature, the diagnostic role of d-dimer for deep venous thrombosis (DVT) or pulmonary embolism (PE) remains unclear, reflecting multiple d-dimer assays and concerns about differing sensitivities and variability.To systematically review trials that assessed sensitivity, specificity, likelihood ratios, and variability among d-dimer assays.Studies in all languages were identified by searching PubMed from 1983 to January 2003 and EMBASE from 1988 to January 2003.The researchers selected prospective studies that compared d-dimer with a reference standard. Studies of high methodologic quality were included in the primary analyses; sensitivity analysis included additional weaker studies.Two authors collected data on study-level factors: d-dimer assay used, cutoff value, and whether patients had suspected DVT or PE.For DVT, the enzyme-linked immunosorbent assay (ELISA) and quantitative rapid ELISA dominate the rank order for these values: sensitivity, 0.96 (95% confidence limit [CL], 0.91 to 1.00), and negative likelihood ratio, 0.12 (CL, 0.04 to 0.33); and sensitivity, 0.96 (CL, 0.90 to 1.00), and negative likelihood ratio, 0.09 (CL, 0.02 to 0.41), respectively. For PE, the ELISA and quantitative rapid ELISA also dominate the rank order for these values: sensitivity, 0.95 (CL, 0.85 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.03 to 0.58); and sensitivity, 0.95 (CL, 0.83 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.02 to 0.84), respectively. The ELISA and quantitative rapid ELISA have negative likelihood ratios that yield a high certainty for excluding DVT or PE. The positive likelihood values, which are in the general range of 1.5 to 2.5, do not greatly increase the certainty of diagnosis. Sensitivity analyses do not affect these findings.Although many studies evaluated multiple d-dimer assays, findings are based largely on indirect comparisons of test performance characteristics across studies.The ELISAs in general dominate the comparative ranking among the d-dimer assays for sensitivity and negative likelihood ratio. For excluding PE or DVT, a negative result on quantitative rapid ELISA is as diagnostically useful as a normal lung scan or negative duplex ultrasonography finding.

Modern diagnostic strategies of venous thromboembolism (VTE) have been developed. In this review, the diagnostic algorithms for deep-vein thrombosis (DVT) and their parameters are discussed individually in the context of reporting a case of DVT in a 43-year-old Caucasian female with a moderate pretest probability stratified by Wells' score and a negative high quality D-dimer test. The patient was on treatment with Xarelto (rivaroxaban), 20 mg PO daily at the time of presentation. The diagnosis was verified through a complete lower limb ultrasound (US). This case highlights the diagnostic challenges and pitfalls of the current algorithms, especially those seen in a subgroup of patients such as patients with cancer, pregnancy, recurrent VTE or are on anticoagulation therapy at the time of presentation. The diagnosis of DVT is less plausible in a patient who is on anticoagulation therapy, but physicians should be aware of such a possibility. Physicians should also know in advance the numerous clinically relevant limitations of D-dimer testing before interpreting the results. Unifying the current diagnostic strategies, modifying the current Wells' score and using the protocol of a whole-leg compression US instead of the limited US protocol are among the several cautious suggestions that have been proposed based on this review to possibly decrease the incidence of missed DVT.© 2020 Al-Khafaji and Schierbeck.

Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy.We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance.We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography.Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data.

To determine, by systematic review of the literature, the prevalence of silent pulmonary embolism in patients with deep venous thrombosis.Twenty-eight included published investigations were identified through PubMed. Studies were selected if methods of diagnosis of pulmonary embolism were described; if pulmonary embolism was stated to be asymptomatic; and if raw data were presented. Studies were stratified according to whether silent pulmonary embolism was diagnosed by a high-probability ventilation-perfusion lung scan using criteria from the Prospective Investigation of Pulmonary Embolism Diagnosis, computed tomography pulmonary angiography, or conventional pulmonary angiography (Tier 1), or by lung scans based on non-Prospective Investigation of Pulmonary Embolism Diagnosis criteria (Tier 2).Silent pulmonary embolism was diagnosed in 1665 of 5233 patients (32%) with deep venous thrombosis. This is a conservative estimate because many of the investigations used stringent criteria for the diagnosis of pulmonary embolism. The incidence of silent pulmonary embolism was higher with proximal deep venous thrombosis than with distal deep venous thrombosis. Silent pulmonary embolism seemed to increase the risk of recurrent pulmonary embolism: 25 of 488 (5.1%) with silent pulmonary embolism versus 7 of 1093 (0.6%) without silent pulmonary embolism.Silent pulmonary embolism sometimes involved central pulmonary arteries. Because approximately one third of patients with deep venous thrombosis have silent pulmonary embolism, routine screening for pulmonary embolism may be advantageous.Copyright 2010 Elsevier Inc. All rights reserved.

To determine the effectiveness of venous compression stockings or compression bandages on the reduction of postthrombotic syndrome in patients with deep venous thrombosis.We attempted to identify all published trials in all languages identified by PubMed through June 2009. Meta-analysis was performed.Based on 5 randomized trials of patients with deep venous thrombosis comparing treatment with venous compression to controls, mild-to-moderate postthrombotic syndrome occurred in 64 of 296 (22%) treated with venous compression, compared with 106 of 284 (37%) in controls (relative risk=0.52). Severe postthrombotic syndrome occurred in 14 of 296 (5%) treated, compared with 33 of 284 (12%) controls (relative risk=0.38). Any postthrombotic syndrome occurred in 89 of 338 (26%) treated, compared with 150 of 324 (46%) controls (relative risk=0.54).Venous compression reduced the incidence of postthrombotic syndrome, particularly severe postthrombotic syndrome. Venous compression in patients with deep venous thrombosis would seem to be indicated for this purpose. There was, however, wide variation in the type of stockings used, time interval from diagnosis to application of stockings, and duration of treatment. Further investigation, therefore, is needed.Copyright 2010 Elsevier Inc. All rights reserved.

Post-thrombotic syndrome (PTS) is a common and burdensome complication of deep venous thrombosis (DVT). Previous trials suggesting benefit of elastic compression stockings (ECS) to prevent PTS were small, single-centre studies without placebo control. We aimed to assess the efficacy of ECS, compared with placebo stockings, for the prevention of PTS.We did a multicentre randomised placebo-controlled trial of active versus placebo ECS used for 2 years to prevent PTS after a first proximal DVT in centres in Canada and the USA. Patients were randomly assigned to study groups with a web-based randomisation system. Patients presenting with a first symptomatic, proximal DVT were potentially eligible to participate. They were excluded if the use of compression stockings was contraindicated, they had an expected lifespan of less than 6 months, geographical inaccessibility precluded return for follow-up visits, they were unable to apply stockings, or they received thrombolytic therapy for the initial treatment of acute DVT. The primary outcome was PTS diagnosed at 6 months or later using Ginsberg's criteria (leg pain and swelling of ≥1 month duration). We used a modified intention to treat Cox regression analysis, supplemented by a prespecified per-protocol analysis of patients who reported frequent use of their allocated treatment. This study is registered with ClinicalTrials.gov, number NCT00143598, and Current Controlled Trials, number ISRCTN71334751.From 2004 to 2010, 410 patients were randomly assigned to receive active ECS and 396 placebo ECS. The cumulative incidence of PTS was 14·2% in active ECS versus 12·7% in placebo ECS (hazard ratio adjusted for centre 1·13, 95% CI 0·73-1·76; p=0·58). Results were similar in a prespecified per-protocol analysis of patients who reported frequent use of stockings.ECS did not prevent PTS after a first proximal DVT, hence our findings do not support routine wearing of ECS after DVT.Canadian Institutes of Health Research.Copyright © 2014 Elsevier Ltd. All rights reserved.

Thus far, the association between residual vein occlusion and immediate compression therapy and postthrombotic syndrome is undetermined. Therefore, we investigated whether compression therapy immediately after diagnosis of deep vein thrombosis affects the occurrence of residual vein obstruction (RVO), and whether the presence of RVO is associated with postthrombotic syndrome and recurrent venous thromboembolism. In a prespecified substudy within the IDEAL (individualized duration of elastic compression therapy against long-term duration of therapy for prevention of postthrombotic syndrome) deep vein thrombosis (DVT) study, 592 adult patients from 10 academic and nonacademic centers across The Netherlands, with objectively confirmed proximal DVT of the leg, received no compression or acute compression within 24 hours of diagnosis of DVT with either multilayer bandaging or compression hosiery (pressure, 35 mm Hg). Presence of RVO and recurrent venous thromboembolism was confirmed with compression ultrasonography and incidence of postthrombotic syndrome as a Villalta score of at least 5 at 6 and 24 months. The average time from diagnosis until assessment of RVO was 5.3 (standard deviation, 1.9) months. A significantly lower percentage of patients who did receive compression therapy immediately after DVT had RVO (46.3% vs 66.7%; odds ratio, 0.46; 95% confidence interval, 0.27-0.80; =.005). Postthrombotic syndrome was less prevalent in patients without RVO (46.0% vs 54.0%; odds ratio, 0.65; 95% confidence interval, 0.46-0.92; =.013). Recurrent venous thrombosis showed no significant association with RVO. Immediate compression should therefore be offered to all patients with acute DVT of the leg, irrespective of severity of complaints. This study was registered at ClinicalTrials.gov (NCT01429714) and the Dutch Trial registry in November 2010 (NTR2597).© 2018 by The American Society of Hematology.

We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics.We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence.For VTE and no cancer, as long-term anticoagulant therapy, we suggest dabigatran (Grade 2B), rivaroxaban (Grade 2B), apixaban (Grade 2B), or edoxaban (Grade 2B) over vitamin K antagonist (VKA) therapy, and suggest VKA therapy over low-molecular-weight heparin (LMWH; Grade 2C). For VTE and cancer, we suggest LMWH over VKA (Grade 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C). We have not changed recommendations for who should stop anticoagulation at 3 months or receive extended therapy. For VTE treated with anticoagulants, we recommend against an inferior vena cava filter (Grade 1B). For DVT, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). For subsegmental pulmonary embolism and no proximal DVT, we suggest clinical surveillance over anticoagulation with a low risk of recurrent VTE (Grade 2C), and anticoagulation over clinical surveillance with a high risk (Grade 2C). We suggest thrombolytic therapy for pulmonary embolism with hypotension (Grade 2B), and systemic therapy over catheter-directed thrombolysis (Grade 2C). For recurrent VTE on a non-LMWH anticoagulant, we suggest LMWH (Grade 2C); for recurrent VTE on LMWH, we suggest increasing the LMWH dose (Grade 2C).Of 54 recommendations included in the 30 statements, 20 were strong and none was based on high-quality evidence, highlighting the need for further research.Copyright © 2016 American College of Chest Physicians. All rights reserved.

This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously.We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology.The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update.New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.Copyright © 2021. Published by Elsevier Inc.

Heparin is a widely used anticoagulant. Because of its negative charge, it forms complexes with positively charged platelet factor 4 (PF4). This can induce anti-PF4/heparin IgG Abs. Resulting immune complexes activate platelets, leading to the prothrombotic adverse drug reaction heparin-induced thrombocytopenia (HIT). HIT requires treatment with alternative anticoagulants. Approved for HIT are 2 direct thrombin inhibitors (DTI; lepirudin, argatroban) and danaparoid. They are niche products with limitations. We assessed the effects of the DTI dabigatran, the direct factor Xa-inhibitor rivaroxaban, and of 2-O, 3-O desulfated heparin (ODSH; a partially desulfated heparin with minimal anticoagulant effects) on PF4/heparin complexes and the interaction of anti-PF4/heparin Abs with platelets. Neither dabigatran nor rivaroxaban had any effect on the interaction of PF4 or anti-PF4/heparin Abs with platelets. In contrast, ODSH inhibited PF4 binding to gel-filtered platelets, displaced PF4 from a PF4-transfected cell line, displaced PF4/heparin complexes from platelet surfaces, and inhibited anti-PF4/heparin Ab binding to PF4/heparin complexes and subsequent platelet activation. Dabigatran and rivaroxaban seem to be options for alternative anticoagulation in patients with a history of HIT. ODSH prevents formation of immunogenic PF4/heparin complexes, and, when given together with heparin, may have the potential to reduce the risk for HIT during treatment with heparin.

Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism.In a multicentre, parallel-group, open-label, randomised study, children (aged 0-17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children <2 years of age with catheter-related venous thromboembolism). The primary efficacy outcome, symptomatic recurrent venous thromboembolism (assessed by intention-to-treat), and the principal safety outcome, major or clinically relevant non-major bleeding (assessed in participants who received ≥1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed.From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87-95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29-35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0·40, 95% CI 0·11-1·41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0·012). Major or clinically relevant non-major bleeding in participants who received ≥1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1·58, 95% CI 0·51-6·27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths.In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants.Bayer AG and Janssen Research & Development.Copyright © 2020 Elsevier Ltd. All rights reserved.

Purpose Venous thromboembolism (VTE) is common in patients with cancer. Long-term daily subcutaneous low molecular weight heparin has been standard treatment for such patients. The purpose of this study was to assess if an oral factor Xa inhibitor, rivaroxaban, would offer an alternative treatment for VTE in patients with cancer. Patient and Methods In this multicenter, randomized, open-label, pilot trial in the United Kingdom, patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE, or symptomatic lower-extremity proximal deep vein thrombosis (DVT) were recruited. Allocation was to dalteparin (200 IU/kg daily during month 1, then 150 IU/kg daily for months 2-6) or rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily for a total of 6 months). The primary outcome was VTE recurrence over 6 months. Safety was assessed by major bleeding and clinically relevant nonmajor bleeding (CRNMB). A sample size of 400 patients would provide estimates of VTE recurrence to within ± 4.5%, assuming a VTE recurrence rate at 6 months of 10%. Results A total of 203 patients were randomly assigned to each group, 58% of whom had metastases. Twenty-six patients experienced recurrent VTE (dalteparin, n = 18; rivaroxaban, n = 8). The 6-month cumulative VTE recurrence rate was 11% (95% CI, 7% to 16%) with dalteparin and 4% (95% CI, 2% to 9%) with rivaroxaban (hazard ratio [HR], 0.43; 95% CI, 0.19 to 0.99). The 6-month cumulative rate of major bleeding was 4% (95% CI, 2% to 8%) for dalteparin and 6% (95% CI, 3% to 11%) for rivaroxaban (HR, 1.83; 95% CI, 0.68 to 4.96). Corresponding rates of CRNMB were 4% (95% CI, 2% to 9%) and 13% (95% CI, 9% to 19%), respectively (HR, 3.76; 95% CI, 1.63 to 8.69). Conclusion Rivaroxaban was associated with relatively low VTE recurrence but higher CRNMB compared with dalteparin.

Direct oral anticoagulants for the treatment of venous thromboembolism are supported by robust clinical trial evidence. Despite published guidance, general practitioners are faced with increasingly complex decisions and implementation remains sub-optimal in certain real-world scenarios.

Catheter-directed thrombolysis (CDT) has been utilized as an adjunct to anticoagulant therapy in selected patients with deep vein thrombosis (DVT) for approximately 30 years. CDT used to be limited to patients with DVT causing acute limb threat and those exhibiting failure of initial anticoagulation, but has expanded over time. Randomized trials evaluating the first-line use of CDT for proximal DVT have demonstrated that CDT does not produce a major reduction in the occurrence of post-thrombotic syndrome (PTS) and that it is poorly suited for elderly patients and those with limited thrombus extent or major risk factors for bleeding. However, CDT does offer selected patients with acute iliofemoral DVT improvement in reducing early DVT symptoms, in achieving reduction in PTS severity, and in producing an improvement in health-related quality of life (QOL). Clinical practice guidelines from medical and surgical societies are now largely aligned with the randomized trial results. This review offers the reader an update on the results of recently completed clinical trials, and additional guidance on appropriate selection of patients with DVT for catheter-directed thrombolytic therapy.

To provide evidence-based recommendations on the use of inferior vena cava (IVC) filters in the treatment of patients with or at substantial risk of venous thromboembolic disease.A multidisciplinary expert panel developed key questions to address in the guideline, and a systematic review of the literature was conducted. Evidence was graded based on a standard methodology, which was used to inform the development of recommendations.The systematic review identified a total of 34 studies that provided the evidence base for the guideline. The expert panel agreed on 18 recommendations.Although the evidence on the use of IVC filters in patients with or at risk of venous thromboembolic disease varies in strength and quality, the panel provides recommendations for the use of IVC filters in a variety of clinical scenarios. Additional research is needed to optimize care for this patient population.Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.

During catheter-directed thrombolysis (CDT), D-dimer (D-D) are generated in large quantities and fibrinogen (FIB) is continuously consumed. Reduction of FIB increases the risk of bleeding. However, there are currently few studies on the relationship between D-D and FIB concentrations during CDT.

Summary: Background: This study sought to compare effectiveness and safety of percutaneous mechanical thrombectomy (PMT) and thrombolysis alone (THR) in patients with acute or subacute iliofemoral deep vein thrombosis (IfDVT). Patients and methods: Observational and randomized trials, published between January 2001 to February 2019 were identified by searching MEDLINE. Studies on deep venous thrombosis (DVT) treated with either THR or PMT adjunctive to conventional anticoagulation and compressive intervention were included. Meta-analysis of proportions was conducted to assess effectiveness outcomes of successful lysis and primary patency, post-thrombotic syndrome (PTS), valvular reflux, recurrent DVT, as well as safety outcomes of major bleeding, hematuria, and pulmonary embolism. Results: Of 77 identified records, 17 studies including 1417 patients were eligible. Pooled proportion of successful lysis was similar between groups (THR: 95 % [I2 = 68.4 %], PMT 96 %, [I2 = 0 %]; Qbet [Cochran’s Q between groups] 0.3, p = 0.61). However, pooled proportion of 6-month primary patency was lower after THR than after PMT (68 % [I2 = 15.6 %] versus 94 %; Qbet 26.4, p < 0.001). Considerable heterogeneity within groups did not allow for between-group comparison of PTS and recurrent DVT. Major bleeding was more frequent after THR than after PMT (6.0 % [I2 = 0 %] versus 1.0 % [I2 = 0 %]; Qbet 12.3, p < 0.001). Incidence of hematuria was lower after THR as compared to PMT (2 % [I2 = 56 %] versus 91.3 % [I2 = 91.7 %]; Qbet 714, p < 0.001). Incidences of valvular reflux and pulmonary embolism were similar across groups (THR: 61 % versus PMT: 53 %; Qbet 0.7, p = 0.39 and THR: 2 % versus PMT: 1 %; Qbet 1.1, p = 0.30, respectively). Conclusions: In patients with iliofemoral DVT, percutaneous mechanical thrombectomy was associated with a higher cumulative 6-month primary patency and a lower incidence of major bleeding compared to thrombolysis alone. Risk of hemolysis from mechanical thrombectomy needs further consideration.

The first-line recommendation for the treatment of acute iliofemoral deep vein thrombosis (IFDVT) is catheter-directed thrombolysis or pharmacomechanical thrombolysis. Recent analysis of surgical thrombectomy has shown comparable results. However, this procedure is not commonly given as much importance as interventional techniques. We analyzed the patient outcome of surgical thrombectomy using modern endovascular techniques in both the short and long term.All consecutive patients who underwent surgical thrombectomy at our institution between April 2008 and April 2017 were included. Only patients with iliofemoral thrombosis, and only those with the first onset of symptoms <10 days, were analyzed. All patients received preoperative duplex ultrasound and contrast-enhanced computed tomography scans for thrombus extension and detection of pulmonary embolism. All operations were performed by vascular surgeons with open and endovascular skills in a C-arm-equipped operating room. During follow-up (FU), all patients received clinical examination for symptoms of postthrombotic syndrome (PTS), as well as duplex ultrasound.Within a 9-year period, 21 patients underwent surgical thrombectomy for IFDVT (17 females/4 males). Primary technical success was 100%; 10 (47.6%) patients received additional primary stenting. 30-day mortality was 0%, 3 patients (14.3%) needed reoperation for early rethrombosis, while secondary 30-day patency was 100%. During FU (median, 6 years; range, 1-104 months), 1 patient received additional stenting for stenosis of the common iliac vein. Nineteen patients (90.5%) presented patent iliofemoral veins without signs of rethrombosis. Two patients (9.5%) died during FU of cancer without signs for recurrent IFDVT. All patients with patent veins were free of symptoms for PTS.Surgical thrombectomy for acute IFDVT is a successful, safe, and durable procedure and provides alternative treatment options for acute IFDVT in selected cases.Copyright © 2017 Elsevier Inc. All rights reserved.

The treatment of venous thromboembolic disease the treatment of choice is systemic anticoagulation. However, the interruption of the inferior vena cava with filters has been recommended when anticoagulation fails or there is a contraindication. Due to the rising inferior vena cava filter (IVCF) complications, physicians are encouraged to retrieve them when there is no longer recommended. In daily practice, it may be a difficult close follow-up of these patients. In this study, the primary objective was to evaluate the IVCF retrieval rate of all implanted filters in a Spanish registry. Secondary objectives were to analyze the causes of failed retrieval, procedure-related complications, and outcomes at a 12-month follow-up.Three hundred fifty-six vena cava filters were implanted in 355 patients. The types of filter were: Gunther Tulip (Cook Medical) 160 (44.9%), Optease (Cordis) 77 (21.6%), Celect (Cook Medical) 49 (13, 7%), Aegisy (Lifetech Scientific) 33 (9.2%), Option ELITE (Argon Medical devices) 16 (4.4%), Denali filter (BD Bard) 11 (3.08%), ALN filter (ALN) 10 (2.8%). Removal was achieved in 274/356 (76,9%). eighty-two (23,1%) IVCF were not retrieved due to the following: 41 (11,5%) patients required ongoing filtration, 24 IVCF (6,7%) patients died before retrieval, and 17 (4,7%) impossibility of retrieval because of a tilted and embedded filter apex. There were no major complications observed.The global retrieval rate of IVCF was achieved in 76.9%, and the adjusted retrieval rate was of 94.15% with no major complications. IVCF tilting was associated with failure of filter removal in less than 5% of cases. This study demonstrates that the retrieval procedure of IVCF is controlled by the clinician and not by the interventional radiologist.

\n \n Background—\n \n In a randomized trial in patients with proximal deep-vein thrombosis, permanent vena cava filters reduced the incidence of pulmonary embolism but increased that of deep-vein thrombosis at 2 years. An 8-year follow-up was performed to assess their very long-term effect.\n

Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), occurs in ∼1 to 2 individuals per 1000 each year, corresponding to ∼300 000 to 600 000 events in the United States annually.These evidence-based guidelines from the American Society of Hematology (ASH) intend to support patients, clinicians, and others in decisions about treatment of VTE.ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and adult patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment.The panel agreed on 28 recommendations for the initial management of VTE, primary treatment, secondary prevention, and treatment of recurrent VTE events.Strong recommendations include the use of thrombolytic therapy for patients with PE and hemodynamic compromise, use of an international normalized ratio (INR) range of 2.0 to 3.0 over a lower INR range for patients with VTE who use a vitamin K antagonist (VKA) for secondary prevention, and use of indefinite anticoagulation for patients with recurrent unprovoked VTE. Conditional recommendations include the preference for home treatment over hospital-based treatment for uncomplicated DVT and PE at low risk for complications and a preference for direct oral anticoagulants over VKA for primary treatment of VTE.

Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy.

Essentials The optimal management of isolated distal deep vein thrombosis (IDDVT) is undefined. This meta-analysis aimed to assess the clinical benefit of anticoagulation for IDDVT. Anticoagulation reduced the rate of pulmonary embolism without increasing major bleeding risk. Recurrent thromboembolism was less common with more than 6 weeks vs. 6 weeks of anticoagulation.Background The optimal management of patients with isolated distal deep vein thrombosis (IDDVT), concerning both the need for anticoagulation and its duration, is undefined. Objectives We performed a meta-analysis of randomized and cohort studies in patients with IDDVT to assess the clinical benefit of: (i) anticoagulation versus no anticoagulation; and (ii) anticoagulant treatment for 6 weeks versus for > 6 weeks. Methods The primary outcome of this analysis was recurrent venous thromboembolism (proximal propagation, recurrence of deep vein thrombosis, and pulmonary embolism). Data were pooled and compared by the use of odds ratio (OR) and 95% confidence interval (CI). Results A reduction in the rate of recurrent venous thromboembolism was observed in patients who received anticoagulation relative to those who did not receive anticoagulation (either therapeutic or prophylactic) (20 studies, 2936 patients; OR 0.50, 95% CI 0.31-0.79), without an increase in the risk of major bleeding (OR 0.64, 95% CI 0.15-2.73). The rate of pulmonary embolism was lower in anticoagulant-treated patients than in controls (15 studies, 1997 patients; OR 0.48, 95% CI 0.25-0.91). A lower rate of recurrent venous thromboembolism was observed in patients who received > 6 weeks of anticoagulant therapy than in those who received 6 weeks of anticoagulant therapy (four studies, 1136 patients; OR 0.39, 95% CI 0.17-0.90). Conclusions In patients with IDDVT, anticoagulation (both therapeutic and prophylactic) reduces the rate of recurrent venous thromboembolism and the incidence of pulmonary embolism as compared with no anticoagulation, without an increased risk of major bleeding. Anticoagulation for > 6 weeks should be preferred over shorter durations.© 2017 International Society on Thrombosis and Haemostasis.

Deep venous thrombosis (DVT) and in particular, iliofemoral thrombosis (IFT) can lead to recurrent thrombosis and postthrombotic syndrome (PTS). Data on the prevalence, predictors and outcome of IFT are scarce. We retrospectively searched our database of outpatients who had presented with DVT and IFT including the iliac veins from 2014 until 2017. In addition, we performed a prospective registry in a subgroup of patients with IFT. These patients received duplex ultrasound, magnetic resonance venography and measurement of symptom-free walking distance using a standardized treadmill ergometry. The severity of PTS was analyzed using the Villalta-Scale (VS) and quality of life was assessed using the VEINES-QOL/Sym Questionnaire. 847 patients were retrospectively identified with DVT and 19.7% (167/847) of these presented with IFT. 50.9% (85/167) of the IFT-patients agreed to participate in the prospective registry. The majority of these patients (76.5%: 65/85) presented with left-sided IFT. In 53.8% (35/65) May-Thurner syndrome was suspected. 27.1% (23/85) underwent invasive therapy. Moderate or severe PTS (VS ≥ 10) occurred in 10.6% (9/85). The severity of PTS is correlated with a reduced quality of life (ρ (CI 95%) = -0.63 (-0.76; -0.46); p < 0.01). None of the patients presented with a venous ulcer at any time. A high body mass index was a significant predictor (OR (CI 95%) = 1.18 (1.05; 1.33), p = 0.007) for the development of clinically relevant PTS (VS ≥ 10) and venous claudication. Every fifth patient with DVT presented with an IFT. The majority developed left sided IFT. Every 10 patient developed moderate or severe PTS (VS ≥ 10). A high body mass index was predictive for the development of PTS and venous claudication.

The postthrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT), occurring in 20-40% of patients. Identifying risk factors for PTS may be useful to provide patients with prognostic information and target prevention strategies.To conduct a systematic review to assess whether, among patients with DVT, inherited and acquired thrombophilias are associated with a risk of PTS.We searched the electronic databases PubMed, EMBASE, Scopus, and Web of Science for studies published from 1990 to 2013 that assessed any thrombophilia in adult DVT patients and its association with the development of PTS. We calculated odds ratios and 95% confidence intervals for PTS according to the presence of thrombophilia. Meta-analysis was performed using the random-effects model.Sixteen studies were included: 13 assessed factor V Leiden (FVL), 10 assessed prothrombin mutation, five assessed protein S and C deficiencies, three assessed antithrombin deficiency, four assessed elevated FVIII levels, and six assessed antiphospholipid antibodies. None of the meta-analyses identified any thrombophilia to be predictive of PTS. Both FVL and prothrombin mutation appeared protective among studies including patients with both first and recurrent DVT and studies in which more than 50% of patients had an unprovoked DVT.Our meta-analysis did not demonstrate a significant association between any of the thrombophilias assessed and the risk of PTS in DVT patients. Other biomarkers in the pathophysiological pathway may be more predictive of PTS.© 2013 International Society on Thrombosis and Haemostasis.

Exercise improves haemodynamic parameters in patients with chronic venous disease. There is a paucity of evidence on its effect in post-thrombotic syndrome (PTS). The aim of this systematic review is to assess the impact of exercise in PTS.

To evaluate the technical aspects and early clinical results of combined stent placement for the management of postthrombotic syndrome (PTS) in chronic total occlusions (CTOs) of the iliofemoral veins.A total of 81 consecutive patients (mean age, 57 y; 37 men; 81 limbs; 65 left limbs) with postthrombotic CTO of the iliofemoral veins treated with combined stent placement in a single institution from January 2013 to December 2014 were retrospectively analyzed. Wallstents were used for femoral inflow and E-Luminexx stents for iliac outflow. Technical aspects, quality of life (QOL), stent patency, and Villalta scores were recorded at follow-up. Primary, primary assisted, and secondary patency rates were estimated with Kaplan-Meier methods with the log-rank test.Percutaneous recanalization was successful in 77 of 81 limbs (95.1%). Stents were deployed in all iliofemoral occlusions, with two stents in 63 lesions (77.8%) lesions and three stents in 18 lesions (22.2%). Venous perforation occurred in 32 patients (37.4%) and was resolved in all cases after stent placement. Back pain occurred during balloon angioplasty (93.8%) and persisted after stent placement in 56.8% of patients. However, the symptoms were self-limiting without further therapy. QOL and Villalta scores were significantly improved during a median follow-up of 19 months (range, 1-38 mo; P <.01). The 2-year primary, primary assisted, and secondary cumulative stent patency rates were 81.5%, 91.4%, and 93.8%, respectively.Combined stent placement is an effective, safe, and feasible method of management of PTS in iliofemoral CTO until commercial venous stents designed for PTS become available.Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

Approximately 10% of all cases of deep vein thrombosis (DVT) occur in the upper extremities. The most common secondary cause of upper-extremity DVT (UEDVT) is the presence of a venous catheter. Primary UEDVT is far less common and usually occurs in patients with anatomic abnormalities of the costoclavicular space causing compression of the subclavian vein, called venous thoracic outlet syndrome (VTOS). Subsequently, movement of the arm results in repetitive microtrauma to the vein and its surrounding structures causing apparent ‘spontaneous’ thrombosis, or Paget-Schrötter syndrome. Treatment of UEDVT aims at elimination of the thrombus, thereby relieving acute symptoms, and preventing recurrence. Initial management for all UEDVT patients consists of anticoagulant therapy. In patients with Paget-Schrötter syndrome the underlying VTOS necessitates a more aggressive management strategy. Several therapeutic options exist, including catheter-directed thrombolysis, surgical decompression through first rib resection, and percutaneous transluminal angioplasty of the vein. However, several controversies exist regarding their indication and timing.

Upper extremity deep vein thrombosis represents (UEDVT) 2-3% of all deep vein thrombosis. Catheter directed thrombolysis (CDT) was replaced largely by pharmacomechanical thrombolysis (PMT) in our institution. In this study we compared the immediate and 1-year results as well as the total hospital costs between CDT and PMT in the treatment of UEDVT.From 2006 to 2013, 55 patients with UEDVT were treated with either CDT or PMT at Helsinki University Hospital. Of them, 43 underwent thoracoscopic rib resection later to relieve phlebography-confirmed vein compression. This patient cohort was prospectively followed up with repeated phlebographies. CDT was performed to 24 patients, and 19 had PMT with a Trellis™ device. Clinical evaluation and vein patency assessment were performed with either phlebography or ultrasound 1 year after the thrombolysis. Primary outcomes were immediate technical success, 1-year vein patency, and costs of the initial treatment.The immediate overall technical success rate, defined as recanalization of the occluded vein and removal of the fresh thrombus, was 91.7% in the CDT group and 100% in the PMT group (n.s.). The median thrombolytic time was significantly longer in CDT patients than that in PMT patients (21.1 vs. 0.33 hr, P < 0.00001). There were no procedure-related complications. The 1-year primary assisted patency rate was similar in both the groups (91.7% and 94.7%). There were no recurrences of clinical DVT. The hospital costs for the acute period were significantly lower in the PMT group than those in the CDT group (medians: 11,476 € and 5,975 € in the CDT and PMT groups, respectively [P < 0.00001]).The clinical results of the treatment of UEDVT with CDT or PMT were similar. However, PMT required shorter hospital stay and less intensive surveillance, leading to lower total costs.Copyright © 2018 Elsevier Inc. All rights reserved.

There is limited data on the occurrence of complications in patients with upper extremity deep vein thrombosis (UEDVT).We aimed to determine the frequency of post-thrombotic syndrome (PTS), thrombosis recurrence and major bleeding (MB) in patients with UEDVT.We conducted a systematic review of the literature including studies from 1970 onwards. We included observational studies, randomized trials, or cases series including >20 patients. We calculated pooled proportions using a random effects model. Subgroup analyses according to etiology and treatment modality were conducted.A total of 62 studies comprising 3550 patients were included. The pooled proportions for PTS and recurrence were 19.4% (95% CI 11.3-27.6) and 7.5% (95% CI 4.1-10.9), respectively. With a mean follow up of 6 months, the proportion of PTS was higher in patients with primary (unprovoked) UEDVT compared to secondary, whereas recurrence was higher in secondary UEDVT. PTS was more frequent in patients treated with anticoagulation alone compared to thrombolysis or surgical decompression. The pooled proportion for MB was 5.0% (95% CI 0.3-9.7) after anticoagulation alone and 3.8% (95% CI: 2.4-5.8%) after thrombolysis and/or surgery.This study suggests that UEDVT is associated with significant rates of PTS and recurrence and its treatment has a relatively low risk of major bleeding. Differences exist depending on etiology and treatment modality.Copyright © 2018 Elsevier Ltd. All rights reserved.

The aims of this study were to analyse the characteristics of patients with internal jugular venous thrombosis. We compared the characteristics of patients with internal jugular venous thrombosis with those of patients exhibiting upper extremity deep venous thrombosis (UEDVT) without internal jugular vein involvement.From 1998 to 2007, 1948 consecutive patients were referred to our Department of Internal Medicine for deep venous thrombosis.Sixty-four patients exhibited UEDVT. Internal jugular venous thrombosis was diagnosed in 29 patients. Twenty-three patients had secondary thrombosis mainly due to cancer, central venous catheter and ovarian hyperstimulation syndrome; three of the four patients with bilateral DVT exhibited cancer. Six patients had primary internal jugular vein thrombosis. Complications of internal jugular vein thrombosis were pulmonary embolism (10.3%) and post-thrombotic syndrome (41.4%). Under multivariate analysis, significant factors for internal jugular vein thrombosis were older patients (P = 0.0008), female gender (P = 0.0035) and ovarian hyperstimulation syndrome (P = 0.0093).Our study underscores that the most common causes of internal jugular vein thrombosis are cancer, central venous catheter and ovarian hyperstimulation syndrome; it also underlines that bilateral internal jugular vein thrombosis is a significant risk indicator of malignancy Thrombosis led to high morbidity related to pulmonary embolism and post-thrombotic syndrome, principally in patients with secondary DVT. The knowledge of predictive factors of internal jugular vein thrombosis seems to be of utmost importance to improve patients' management.

(1) Background: internal jugular vein thrombosis (IJVthr) is a potentially life-threating disease but no comprehensive reviews on etiology, symptomatology, diagnosis and current treatment guidelines are yet available; (2) Methods: we prospectively developed a protocol that defined objectives, search strategy for study identification, criteria for study selection, data extraction, study outcomes, and statistical methodology, according to the PRISMA standard. We performed a computerized search of English-language publications listed in the various electronic databases. We also retrieved relevant reports from other sources, especially by the means of hand search in the Glauco Bassi Library of the University of Ferrara; (3) Results: using the predefined search strategy, we retrieved and screened 1490 titles. Data from randomized control trials were few and limited to the central vein catheterization and to the IJVthr anticoagulation treatment. Systematic reviews were found just for Lemierre syndrome, the risk of pulmonary embolism, and the IJVthr following catheterization. The majority of the information required in our pre-defined objectives comes from perspectives observational studies and case reports. The methodological quality of the included studies was from moderate to good. After title and abstract evaluation, 1251 papers were excluded, leaving 239 manuscripts available. Finally, just 123 studies were eligible for inclusion. We found out the description of 30 different signs, symptoms, and blood biomarkers related to this condition, as well as 24 different reported causes of IJVthr. (4) Conclusions: IJVthr is often an underestimated clinical problem despite being one of the major sources of pulmonary embolism as well as a potential cause of stroke in the case of the upward propagation of the thrombus. More common symptoms are neck pain and headache, whereas swelling, erythema and the palpable cord sign beneath the sternocleidomastoid muscle, frequently associated with fever, are the most reported clinical signs. An ultrasound of the neck, even limited to the simple and rapid assessment of the compression maneuver, is a quick, economic, cost-effective, noninvasive tool. High quality studies are currently lacking.