Search

Background and Objective: Compression therapy following deep venous thrombosis in the Netherlands is suboptimal. We assessed the budget impact of targeted care improvements. Methods: We calculated the per-patient and population healthcare resource use and costs concerning 26,500 new patients each year in the Netherlands for the current pathways in region North Holland (divided into two parts: NH-A and NH-B) and region Limburg. Next, we assessed the impact of three improvement targets: optimizing initial compression therapy, early consultation of an occupational therapist, and tailored duration of elastic compression stocking therapy. Inputs were based on interview (n = 30) and survey data (n = 114), literature, and standard prices. The robustness of the results was tested by sensitivity analyses. Results: The current per-patient costs for a 2-year episode were €1046 (NH-A), €947 (NH-B), and €1256 (Limburg). The improvements led to direct savings for region Limburg (€4.7 million). Population costs increased in the first year for NH-A (+ €3.5 million) and NH-B (+ €6.4 million), and decreased in the second and third year resulting in a cost reduction for NH-A (− €2.2 million) but not for NH-B (+ €0.6 million). Workload for occupational therapists and internists in North Holland increased, and workload for home care nurses decreased in all regions. Conclusions: This study provides a detailed insight into current costs and healthcare resource use associated with compression therapy and the potential impact of implementing three improvement targets. We showed that the improvements resulted in considerable cost savings within 3 years after implementation for region NH-A and Limburg.

The Fourth Maastricht Consensus Conference on Thrombosis included the following themes. Theme 1: The “coagulome” as a critical driver of cardiovascular disease. Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow, and kidney. Four investigators shared their views on these organ-specific topics. Theme 2: Novel mechanisms of thrombosis. Mechanisms linking factor XII to fibrin, including their structural and physical properties, contribute to thrombosis, which is also affected by variation in microbiome status. Virus infection-associated coagulopathies perturb the hemostatic balance resulting in thrombosis and/or bleeding. Theme 3: How to limit bleeding risks: insights from translational studies. This theme included state-of-the-art methodology for exploring the contribution of genetic determinants of a bleeding diathesis; determination of polymorphisms in genes that control the rate of metabolism by the liver of P2Y12 inhibitors, to improve safety of antithrombotic therapy. Novel reversal agents for direct oral anticoagulants are discussed. Theme 4: Hemostasis in extracorporeal systems: the value and limitations of ex vivo models. Perfusion flow chamber and nanotechnology developments are developed for studying bleeding and thrombosis tendencies. Vascularized organoids are utilized for disease modeling and drug development studies. Strategies for tackling extracorporeal membrane oxygenation-associated coagulopathy are discussed. Theme 5: Clinical dilemmas in thrombosis and antithrombotic management. Plenary presentations addressed controversial areas, i.e., thrombophilia testing, thrombosis risk assessment in hemophilia, novel antiplatelet strategies, and clinically tested factor XI(a) inhibitors, both possibly with reduced bleeding risk. Finally, COVID-19-associated coagulopathy is revisited.

Contains fulltext : 245942.pdf (Publisher’s version ) (Open Access)

Aims Evidence regarding the health burden of chronic venous insufficiency (CVI), its clinical determinants, and impact on outcome is scarce. Methods and results Systematic phenotyping of CVI according to established CEAP (Clinical-Etiologic-Anatomic-Pathophysiologic) classification was performed in 12 423 participants (age range: 40–80 years) of the Gutenberg Health Study from April 2012 to April 2017. Prevalence was calculated age- and sex-specifically. Multivariable Poisson regression models were calculated to evaluate the relation of CVI with cardiovascular comorbidities. Survival analyses were carried out to assess the CVI-associated risk of death. Replication of findings was done in an independent cohort study (MyoVasc, NCT04064450). The prevalence of telangiectasia/reticular, varicose veins, and CVI was 36.5% [95% confidence interval (CI), 35.6–37.4%], 13.3% [12.6–13.9%], and 40.8% [39.9–41.7%], respectively. Age, female sex, arterial hypertension, obesity, smoking, and clinically overt cardiovascular disease were identified as clinical determinants of CVI. Higher CEAP classes were associated with a higher predicted 10-year risk for incident cardiovascular disease in individuals free of cardiovascular disease (n = 9923). During a mean follow-up of 6.4 ± 1.6 years, CVI was a strong predictor of all-cause death independent of the concomitant clinical profile and medication [hazard ratio (HR) 1.46 (95% CI 1.19–1.79), P = 0. 0003]. The association of CVI with an increased risk of all-cause death was externally validated in the MyoVasc cohort [HR 1.51 (95% CI 1.11–2.05), P = 0.009]. Conclusion Chronic venous insufficiency is highly prevalent in the population and is associated with the presence of cardiovascular risk factors and disease. Individuals with CVI experience an elevated risk of death, which is independent of age and sex, and present cardiovascular risk factors and comorbidities.

Background: Long-term treatment with direct oral anticoagulants (DOAC) is required for the majority of patients with nonvalvular atrial fibrillation (AF) to prevent ischemic stroke and systemic embolism. Adherence to therapy may impact clinical outcomes. Therefore, the purpose of this study was to assess the potential impact of structured follow-up on long-term adherence to DOAC therapy compared to standard care. Methods: This is a cross sectional study on the implementation phase of medication adherence to DOACs, comparing patients with AF following completion of structured follow-up of minimally 1 year with those who received standard care. All patients used DOACs for more than 2 years and completed a questionnaire on adherence. Adherence was measured with the Morisky Medication Adherence Scale-8 (MMAS-8) score and assessed via an online web portal. Results: A total of 212 patients were included. The mean MMAS-8 score was 7.55 (SD 0.93) after structured follow-up and 7.25 (SD 1.01) for standard care; p = 0.045. Following structured follow-up 64.1% of patients had a high adherence (MMAS score of 8) compared to 50% receiving standard care; p = 0.05. Patients following structured follow-up on a once daily DOAC regime had higher MMAS-8 scores compared to those on a twice daily regime; 7.74 (SD 0.74) versus 7.00 (SD 1.22); p < 0.001. The rates of minor bleedings were 10.6% versus 21.4% respectively, p = 0.038. Conclusion: In patients on long-term DOAC treatment, adherence to therapy was significantly increased after receiving an initial period of structured follow-up compared to standard care. Additionally, adherence to DOAC therapy was higher with once-daily treatment regimen. Significant more minor bleedings were reported in the standard care group. These results indicate that implementation of structured follow-up of patients with AF using DOACs merits further evaluation.

Venous stenting has become a common treatment option for central deep venous outflow obstructions and postthrombotic syndrome. Following successful recanalization and stenting, stent patency is endangered by in‐stent thrombosis and recurrent venous thromboembolism. Antithrombotic therapy might reduce patency loss. This systematic review summarizes the literature on antithrombotic therapy following (post)thrombotic venous stenting. A systematic PubMed, MEDLINE, EMBASE, and Cochrane search was performed for studies addressing antithrombotic therapy prescribed following venous stenting of the iliofemoral tract indicated by acute or chronic thrombotic pathology. A total of 277 articles was identified of which 64 (56 original studies) were selected. Overall, a mean primary patency rate of 82.3% was seen 1 year after the intervention, which decreased to 73.3% after 2 years. In the majority (43 of 56 studies, 77%), treatment was based on use of vitamin K antagonists, either with (18%) or without (59%) use of antiplatelet drugs. Only two studies (4%) directly assessed the effect of antithrombotic therapy on treatment outcomes. The impact of postinterventional antithrombotic therapy on stent patency remains unknown because of limited and insufficient data available in current literature. Further clinical research should more clearly address the role of antithrombotic therapy for preservation of long‐term patency following venous stenting.

Objectives Magnetic resonance venography (MRV) is underutilized in the evaluation of thrombus properties prior to endovascular treatment but may improve procedural outcomes. We therefore investigated the clinical impact of using a dedicated MRV scoring system to assess thrombus characteristics prior to endovascular intervention for iliofemoral deep vein thrombosis (DVT). Methods This is a post hoc analysis of data from the CAVA trial (Clinicaltrials.gov:NCT00970619). MRV studies of patients receiving ultrasound-accelerated catheter-directed thrombolysis (CDT) for iliofemoral DVT were reviewed. Thrombus age-related imaging characteristics were scored and translated into an overall score (acute, subacute, or old). MRV scores were compared to patient-reported complaints. MRV-scored groups were compared for CDT duration and success rate. Results Fifty-six patients (29 men; age 50.8 ± 16.4 years) were included. Using MRV, 27 thrombi were classified acute, 17 subacute, and 12 old. Based on patient-reported complaints, 11 (91.7%) of these old thrombi would have been categorized acute or subacute, and one (3.7%) of the acute thrombi as old. Average duration of CDT to > 90% restored patency differed significantly between groups (p < 0.0001): average duration was 23 h for acute thromboses (range: 19–25), 43 h for subacute (range: 41–62), and 85 h for old thromboses (range: 74–96). CDT was almost eleven times more successful in thromboses characterized as acute and subacute compared to old thromboses (OR: 10.7; 95% CI 2.1–55.5). Conclusion A dedicated MRV scoring system can safely discriminate between acute, subacute, and old thromboses. MRV-based selection is predictive of procedural duration and success rate and can help avoid unnecessary complications. Key Points • Thrombus age, characterized by MRV as acute, subacute, and old, can predict CDT duration and probability of success. • Accurate pre-interventional MRV-based thrombus aging has the potential to facilitate identification of eligible patients and may thus prevent CDT-related complications.

ObjectiveElastic compression stocking (ECS) therapy is commonly used in patients with deep venous thrombosis (DVT) and chronic venous disease (CVD). The provision of ECS therapy is complex, and studies indicate a lack of practical guidance and suboptimal collaboration among health care professionals. We aimed to reach consensus on critical issues of ECS therapy among the involved health care professionals and patients.MethodsA three-round modified Delphi analysis was performed in the Netherlands in which 56 health care professionals (internists, dermatologists, general practitioners, emergency room nurses, home care nurses, medical stocking suppliers, and occupational therapists) and seven patients were invited. The 21 statements included in this analysis were based on information collected from a previously conducted Functional Resonance Analysis Method and Realist Evaluation. We used 7-point Likert scale questions and a 75% threshold for consensus.ResultsOf the 63 persons invited for this study, 59 (94%) agreed to participate and responded in the first questionnaire round; of whom 52 were health care professionals and seven were patients (five DVT and two CVD). The overall response rate for the three questionnaire rounds was 91%. After completion of the rounds, full consensus was achieved on 19 out of 21 statements. No consensus was reached on the need for a follow-up appointment for CVD patients and who should be responsible to determine the ECS type (custom-made or standard).ConclusionWe identified 19 consensus-driven recommendations on treatment decisions and collaboration in ECS therapy among an interdisciplinary panel of health care professionals and patients. These recommendations form a basis for consensus-driven optimization of ECS therapy and should ideally be incorporated in a general cross-domain protocol for ECS therapy in patients with DVT and CVD.

Background Dual pathway inhibition with 2.5 mg rivaroxaban twice daily plus 100 mg aspirin once daily may be a promising alternative to 100 mg aspirin antiplatelet therapy for the prevention of cardiovascular events in patients with coronary artery disease and/or peripheral arterial disease. However, treatment costs and bleeding risks are higher, and there is another treatment option for peripheral arterial disease, 75 mg clopidogrel. A comprehensive assessment of benefits, risks and costs of dual pathway inhibition versus standard of care is needed. Methods We used a state transition model including cardiovascular, ischaemic limb and bleeding events to compare dual pathway inhibition to aspirin antiplatelet therapy in coronary artery disease, and additionally to clopidogrel antiplatelet therapy in peripheral arterial disease patients. We calculated the incremental cost-effectiveness ratio from costs and quality-adjusted life-years of lifelong treatment, and the cost-effectiveness probability at a €50,000/quality-adjusted life-year threshold. Results Quality-adjusted life-years and costs of dual pathway inhibition were highest, the incremental cost-effectiveness ratios versus aspirin were €32,109 in coronary artery disease and €26,381 in peripheral arterial disease patients, with 92% and 56% cost-effectiveness probability, respectively (clopidogrel was extendedly dominated). Incremental cost-effectiveness ratios were below €20,000 in comorbid peripheral arterial disease patients and coronary artery disease patients younger than 65 years, incremental cost-effectiveness ratios were above €50,000 in carotid artery disease patients and coronary artery disease patients older than 75 years. Conclusion Lifelong preventive treatment of coronary artery disease and peripheral arterial disease patients at risk of cardiovascular events with dual pathway inhibition improves health outcomes and seems overall cost-effective relative to aspirin antiplatelet therapy and also to clopidogrel antiplatelet therapy for peripheral arterial disease, particularly in comorbid patients, but not in older patients and in carotid artery disease patients. These findings may warrant a targeted approach.

Background: A previous individual participant data (IPD) meta-analysis showed that the Wells rule and D-dimer testing cannot exclude suspected deep vein thrombosis (DVT) in cancer patients. Objectives: To explore reasons for this reduced diagnostic accuracy and to optimize the diagnostic pathway for cancer patients suspected of DVT. Patients and Methods: Using IPD from 13 studies in patients with suspected DVT, DVT prevalence and the predictive value of the Wells rule items and D-dimer testing were compared between patients with and without cancer. Next, we developed a prediction model with five variables selected from all available diagnostic predictors. Results: Among the 10 002 suspected DVT patients, there were 834 patients with cancer. The median prevalence of DVT in these patients with cancer was 37.5% (interquartile range [IQR], 30.8-45.5), whereas it was 15.1% (IQR, 11.5-16.7) in patients without cancer. Diagnostic performance of individual Wells rule items and D-dimer testing was similar across patients with and without cancer, except “immobility” and “history of DVT.” The newly developed rule showed a pooled c-statistic 0.80 (95% confidence interval [CI], 0.75-0.83) and good calibration. However, using this model, still only 4.3% (95% CI, 3.0-5.7) of the suspected patients with cancer could be identified with a predicted DVT posttest probability of

BACKGROUND/OBJECTIVES: Nursing home (NH) residents are a vulnerable population, susceptible to respiratory disease outbreaks such as coronavirus disease 2019 (COVID-19). Poor outcome in COVID-19 is at least partly attributed to hypercoagulability, resulting in a high incidence of thromboembolic complications. It is unknown whether commonly used antithrombotic therapies may protect the vulnerable NH population with COVID-19 against mortality. This study aimed to investigate whether the use of oral antithrombotic therapy (OAT) was associated with a lower mortality in NH residents with COVID-19. DESIGN: A retrospective case series. SETTING: Fourteen NH facilities from the NH organization Envida, Maastricht, the Netherlands PARTICIPANTS: A total of 101 NH residents with COVID-19 were enrolled. MEASUREMENTS: The primary outcome was all-cause mortality. The association between age, sex, comorbidity, OAT, and mortality was assessed using logistic regression analysis. RESULTS: Overall mortality was 47.5% in NH residents from 14 NH facilities. Age, comorbidity, and medication use were comparable among NH residents who survived and who died. OAT was associated with a lower mortality in NH residents with COVID-19 in the univariable analysis (odds ratio (OR) = 0.89; 95% confidence interval (CI) = 0.41-1.95). However, additional adjustments for sex, age, and comorbidity attenuated this difference. Mortality in males was higher compared with female residents (OR = 3.96; 95% CI = 1.62-9.65). Male residents who died were younger compared with female residents (82.2 (standard deviation (SD) = 6.3) vs 89.1 (SD = 6.8) years; P < .001). CONCLUSION: NH residents in the 14 facilities we studied were severely affected by the COVID-19 pandemic, with a mortality of 47.5%. Male NH residents with COVID-19 had worse outcomes than females. We did not find evidence for any protection against mortality by OAT, necessitating further research into strategies to mitigate poor outcome of COVID-19 in vulnerable NH populations. J Am Geriatr Soc 68:1647-1652, 2020.

Background: In patients with a venous outflow obstruction following iliofemoral deep vein thrombosis stenting of the venous tract to prevent or alleviate postthrombotic syndrome is applied with increasing frequency. The impact of the quality of anticoagulant therapy with vitamin K antagonists (VKAs) on the development of in-stent thrombosis is currently unknown.Objectives: To determine the association between the quality of postinterventional VKA treatment and the occurrence of in-stent thrombosis.Methods: Seventy-nine patients with iliofemoral and/or caval venous stent placement for obstruction of the venous outflow were included in this study. All patients received postinterventional VKA. The quality of VKA anticoagulant therapy was expressed as the time within therapeutic range (TTR) calculated using the linear interpolation method and as the proportion of International Normalized Ratio (INR) values Results: In-stent thrombosis developed in 16 patients (20.3%). The total population had a mean TTR of 64.0% (19.0) and a mean proportion of INR values Conclusions: We conclude that the quality of anticoagulant treatment reflected in the TTR following a venous stenting procedure is an important independent determinant for the risk of in-stent thrombosis. The role of anticoagulant treatment for the prevention of in-stent thrombosis following stenting procedures therefore merits further research.

ObjectivesElastic compression stocking (ECS) therapy is an important treatment for patients with deep venous thrombosis (DVT) and chronic venous insufficiency (CVI). This study aimed to provide insight into the structure and variability of the ECS therapy process, its effects on outcomes, and to elicit improvement themes from a multiple stakeholder perspective.DesignThirty semi-structured interviews with professionals and patients were performed. The essential functions for the process of ECS therapy were extracted to create two work-as-done models using the Functional Resonance Analysis Method (FRAM). These findings were used to guide discussion between stakeholders to identify improvement themes.SettingTwo regions in the Netherlands, region Limburg and region North-Holland, including an academic hospital and a general hospital and their catchment region.ParticipantsThe interviewees were purposely recruited and included 25 healthcare professionals (ie, general practitioners, internists, dermatologists, nurses, doctor’s assistants, occupational therapists, home care nurses and medical stocking suppliers) and 5 patients with DVT or CVI.ResultsTwo FRAM models were created (one for each region). The variability of the functions and their effect on outcomes, as well as interdependencies between functions, were identified. These were presented in stakeholder meetings to identify the structure of the process and designated variable and uniform parts of the process and its outcomes. Ultimately, six improvement themes were identified: dissemination of knowledge of the entire process; optimising and standardising initial compression therapy; optimising timing to contact the medical stocking supplier (when oedema has disappeared); improving the implementation of assistive devices; harmonising follow-up duration for patients with CVI; personalising follow-up and treatment duration in patients with DVT.ConclusionsThis study provided a detailed understanding of how ECS therapy is delivered in daily practice by describing major functions and variability in performances and elicited six improvement themes from a multistakeholder perspective.

Objectives: Decision makers adopt health technologies based on health economic models that are subject to uncertainty. In an ideal world, these models parameterize all uncertainties and reflect them in the cost-effectiveness probability and risk associated with the adoption. In practice, uncertainty assessment is often incomplete, potentially leading to suboptimal reimbursement recommendations and risk management. This study examines the feasibility of comprehensive uncertainty assessment in health economic models.Methods: A state transition model on peripheral arterial disease treatment was used as a case study. Uncertainties were identified and added to the probabilistic sensitivity analysis if possible. Parameter distributions were obtained by expert elicitation, and structural uncertainties were either parameterized or explored in scenario analyses, which were model averaged.Results: A truly comprehensive uncertainty assessment, parameterizing all uncertainty, could not be achieved. Expert elicitation informed 8 effectiveness, utility, and cost parameters. Uncertainties were parameterized or explored in scenario analyses and with model averaging. Barriers included time and resource constraints, also of clinical experts, and lacking guidance regarding some aspects of expert elicitation, evidence aggregation, and handling of structural uncertainty. The team's multidisciplinary expertise and existing literature and tools were facilitators.Conclusions: While comprehensive uncertainty assessment may not be attainable, improvements in uncertainty assessment in general are no doubt desirable. This requires the development of detailed guidance and hands-on tutorials for methods of uncertainty assessment, in particular aspects of expert elicitation, evidence aggregation, and handling of structural uncertainty. The issue of benefits of uncertainty assessment versus time and resources needed remains unclear.

Background: Previous prediction models for recurrent thromboembolism (VTE) are often complicated to apply and have not been implemented widely.Aim: To develop and internally validate a potential new prediction model for recurrent VTE that can be used without stopping anticoagulant treatment for D-dimer measurements in patients with provoked and unprovoked DVT.Methods: Cohort data of 479 patients treated in a clinical care pathway at Maastricht University Medical Center were used. Predictors for the Cox proportional hazards model (unprovoked DVT, male gender, factor VIII levels) were derived from literature and using forward selection procedure. The scoring rule was internally validated using bootstrapping techniques and the predictive ability was compared to existing prediction models.Results: Patients were followed for a median of 3.12 years after stopping anticoagulation treatment (IQR 0.78, 3.90). Sixty-four of 479 patients developed recurrent VTE (13%). The scoring rule consisted of unprovoked DVT (yes: 2 points), male sex (yes: 1 point), and factor VIII > 213 % (yes: 2 points) and was categorized into three groups [i.e., low risk (score 0), medium risk (scores 1, 2, or 3) and high risk (scores 4 and 5)]. The concordance statistic was 0.68 (95% CI: 0.61, 0.75).Conclusion: The discriminative ability of the new Continu-8 score was adequate. Future studies shall verify this score in an independent setting without stopping anticoagulation treatment.

Background The CAVA (Ultrasound‐Accelerated Catheter‐Directed Thrombolysis Versus Anticoagulation for the Prevention of Post‐Thrombotic Syndrome) trial did not show a reduction of post‐thrombotic syndrome (PTS) after additional ultrasound‐accelerated catheter‐directed thrombolysis in patients with acute iliofemoral deep vein thrombosis at 1‐year follow‐up. This prespecified analysis of the CAVA trial aimed to determine the impact of additional thrombolysis on outcomes of PTS at long‐term follow‐up. Methods and Results Patients aged 18 to 85 years with a first‐time acute iliofemoral deep vein thrombosis were included and randomly assigned (1:1) to either standard treatment plus ultrasound‐accelerated catheter‐directed thrombolysis or standard treatment alone. The primary outcome was the proportion of PTS (Villalta score ≥5 on 2 occasions ≥3 months apart or venous ulceration) at the final follow‐up visit. Additionally, PTS according to the International Society on Thrombosis and Haemostasis (ISTH) consensus definition was assessed to allow external comparability. Major bleedings were the main safety outcome. At a median follow‐up of 39.0 months (interquartile range, 23.3–63.8), 120 patients (79.8%) participated in the final follow‐up visit: 62 from the intervention group and 58 from the standard treatment group. PTS developed in 19 (30.6%) versus 26 (44.8%) patients, respectively (odds ratio [OR], 0.54; 95% CI, 0.26 to 1.15 [ P =0.11]), with an absolute difference between groups of −14.2% (95% CI, −32.0% to 4.8%). Using the ISTH consensus definition, a significant reduction in PTS was observed (29 [46.8%] versus 40 [69.0%]) (OR, 0.40; 95% CI, 0.19–0.84 [ P =0.01]) with an absolute difference between groups of −22.2% (95% CI, −39.8% to −2.8%). No new major bleedings occurred following the 12‐month follow‐up. Conclusions The impact of additional ultrasound‐accelerated catheter‐directed thrombolysis on the prevention of PTS was found to increase with time. Although this study was limited by its sample size, the overall findings indicate a reduction of mild PTS without impact on quality of life. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00970619.

Background The role of venous obstructions as a risk factor for recurrent venous thromboembolism has never been evaluated. This study aimed to determine whether there is a difference in prevalence of venous obstructions between patients with and without recurrent venous thromboembolism. Furthermore, its influence on the development of post-thrombotic syndrome and patient-reported quality of life was assessed. Methods This matched nested case-control study included 32 patients with recurrent venous thromboembolism (26 recurrent deep-vein thrombosis and 6 pulmonary embolism) from an existing prospective cohort of deep-vein thrombosis patients and compared them to 24 age and sex matched deep-vein thrombosis patients without recurrent venous thromboembolism. All participants received standard post-thrombotic management and underwent an additional extensive duplex ultrasonography. Post-thrombotic syndrome was assessed by the Villalta-scale and quality of life was measured using the SF36v2 and VEINES-QOL/Sym-questionnaires. Results Venous obstruction was found in 6 patients (18.8%) with recurrent venous thromboembolism compared to 5 patients (20.8%) without recurrent venous thromboembolism (Odds ratio 0.88, 95%CI 0.23–3.30, p = 1.000). After a median follow-up of 60.0 months (IQR 41.3–103.5) the mean Villalta-score was 5.55 ± 3.02 versus 5.26 ± 2.63 (p = 0.909) and post-thrombotic syndrome developed in 20 (62.5%) versus 14 (58.3%) patients, respectively (Odds ratio 1.19, 95%CI 0.40–3.51, p = 0.752). If venous obstruction was present, it was mainly located in the common iliac vein (n = 7, 63.6%). In patients with an objectified venous obstruction the mean Villalta-score was 5.11 ± 2.80 versus 5.49 ± 2.87 in patients without venous obstruction (p = 0.639). Post-thrombotic syndrome developed in 6 (54.5%) versus 28 (62.2%) patients, respectively (Odds ratio 1.37, 95%CI 0.36–5.20, p = 0.736). No significant differences were seen regarding patient-reported quality of life between either groups. Conclusions In this exploratory case-control study patients with recurrent venous thromboembolism did not have a higher prevalence of venous obstruction compared to patients without recurrent venous thromboembolism. The presence of recurrent venous thromboembolism or venous obstruction had no impact on the development of post-thrombotic syndrome or the patient-reported quality of life.

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 syndromeas 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; P = .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; P = .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).

Background Bleeding is a feared adverse event during anticoagulant treatment. In patients on vitamin K antagonists, most bleedings occur with the international normalized ratio (INR) in the therapeutic range. Currently, identification of high-risk patients via laboratory methods is not reliable. In this systematic review, we assessed the ability of calibrated automated thrombin generation (CAT-TG) to predict bleeding in patients on anticoagulant treatment. Methods A systematic search was executed in three databases: Medline, Embase, and Cochrane. Results Seven studies were included; two were of good methodological quality. One study showed that patients on warfarin with INRs in range (2–3) admitted for hemorrhage (n = 28), had lower CAT-TG levels (endogenous thrombin potential [ETP]: 333 ± 89 nM/min) than patients on warfarin admitted for other reasons (ETP: 436 ± 207 nM/min; p Conclusion Studies investigating the direct association between decreased CAT-TG values and hemorrhagic events are rare. Therefore, the clinical consequences of low CAT-TG values remain to be further investigated.

Essentials Post thrombotic syndrome (PTS) is a complication of deep vein thrombosis (DVT) with limited treatment options.Uniformity of the diagnostic strategy and the use of risk prediction models might improve treatment outcomes.Extending knowledge on the pathophysiology and improving therapeutic options is paramount for progress. PTS management should evolve to a multimodal approach with treatment tailored to individual patients' needs. Post thrombotic syndrome (PTS) is a common chronic complication of deep vein thrombosis of the leg (DVT). Treatment options are limited therefore emphasis is placed on its prevention. Several risk factors have been recognized, but were so far not used for risk stratification or translation into prediction models. Early interventions did not yet result in more successful preventive treatment strategies; for the acute phase of DVT there is equipoise on the value of elastic compression, as well as on catheter directed thrombolysis. There are no drugs specifically targeted at PTS prevention. The use of anticoagulant medication such as direct oral anticoagulants (DOACs) might decrease PTS incidence, but this needs to be corroborated. Both research into more effective treatment options as well as future PTS management may benefit from a uniform diagnostic strategy and the use of prediction rules to better allocate treatment and thereby increase treatment efficacy.

Background: Finding the optimal duration of anticoagulant treatment following an acute event of deep vein thrombosis (DVT) is challenging. Residual venous obstruction (RVO) has been identified as a risk factor for recurrence, but data on management strategies incorporating the presence of RVO and associated recurrence rates in defined clinical care pathways (CCP) are lacking.Objectives: We aimed to investigate the long-term clinical outcomes and predictors of venous thromboembolism (VTE) recurrence in a contemporary cohort of patients with proximal DVT and managed in a CCP incorporating the presence of RVO.Patients: All patients treated at the Maastricht University Medical Center within an established clinical care pathway from June 2003 through June 2013 were prospectively followed for up to 11 years in a prospective management study.Results: Of 479 patients diagnosed with proximal DVT, 474 completed the two-year CCP (99%), and 457 (94.7%) the extended follow-up (2231.2 patient-years; median follow-up 4.6 years). Overall VTE recurrence was 2.9 per 100 patient-years, 1.3 if provoked by surgery, 2.1 if a non-surgical transient risk factor was present and 4.0 if unprovoked. Predictors of recurrent events were unprovoked VTE (adjusted hazard ratio [HR] 4.6; 95% CI 1.7, 11.9), elevated D-dimer one month after treatment was stopped (HR 3.3; 1.8, 6.1), male sex (HR 2.8; 1.5, 5.1), high factor VIII (HR 2.2; 1.2, 4.0) and use of contraceptives (HR 0.1; 0.0, 0.9).Conclusions: Patients with DVT managed within an established clinical care pathway incorporating the presence of RVO had relatively low incidences of VTE recurrence.

Background Traditional coagulation tests are included in emergency guidelines for management of patients on direct oral anticoagulants (DOACs) who experience acute bleeding or require surgery. We determined the ability of traditional coagulation tests and fast whole blood thromboelastography (ROTEM®) to screen for anticoagulation activity of dabigatran and rivaroxaban as low as 30 ng/mL. Methods One hundred eighty-four citrated blood samples (75 dabigatran, 109 rivaroxaban) were collected from patients with non-valvular atrial fibrillation (NVAF), to perform screening tests from different manufacturers, (diluted, D) PT, aPTT, TT and ROTEM®. The activity of DOACs was quantitatively determined by clot detection assays: Hemoclot DTT and DiXaI test (Biophen), on CS2100 (Siemens). The clotting time (CT) of INTEM and EXTEM ROTEM® (Werfen) were used as test parameters. Results Dabigatran, ≥ 30 ng/mL, was accurately detected by five coagulation tests: APTT Actin FSL (93%), PT Neoplastin (93%), APTT Cephascreen, Thromboclotin, and Thrombin (all 100%), but not by PT Innovin (49%). CT-EXTEM (91%) was sufficiently sensitive, but not CT-INTEM (52%). APTT Cephascreen and Thrombin showed good linearity (R2 = 0.71,R2 = 0.72). For the other tests linearity was moderate to poor. Rivaroxaban was accurately detected by PT Neoplastin (98%) and less so by APTT Cephascreen (85%). In addition, rivaroxaban was also accurately detected by CT-INTEM (96%). PT Neoplastin showed good linearity (R2 = 0.81), all other tests had moderate to poor linearity. Conclusion In patients with NVAF, the ability of routine coagulation tests to detect the presence of significant levels of DOACs is test and reagent dependent. CT-INTEM and CT-EXTEM may be fast whole blood alternatives. Trial registration The Institutional Review Board of the MUMC approved this study (December 2011, project number 114069).

Background: Therapy with elastic compression stockings has been the cornerstone for prevention of post-thrombotic syndrome for decades in patients after acute deep venous thrombosis. It is uncertain who benefits most from therapy, and what the optimum duration of therapy should be. We therefore aimed to assess the safety and efficacy of individualised duration of compression therapy versus the standard duration of 24 months following an initial treatment period of 6 months. Methods: We did a multicentre, randomised, single-blind, allocation-concealed, non-inferiority trial at 12 hospitals in the Netherlands and two in Italy. We randomly assigned patients (1:1) with acute proximal deep vein thrombosis of the leg and without pre-existent venous insufficiency (Clinical Etiological Anatomical and Pathophysiological score

Background: Early thrombus removal might prevent post-thrombotic syndrome by preserving venous function and restoring flow. Previous trials comparing additional catheter-directed thrombolysis to standard treatment showed conflicting outcomes. We aimed to assess the benefit of additional ultrasound-accelerated catheter-directed thrombolysis for the prevention of post-thrombotic syndrome compared with standard therapy in patients with iliofemoral deep-vein thrombosis. Methods: We did a multicentre, randomised, single-blind, allocation-concealed, parallel group, superiority trial in 15 hospitals in the Netherlands. Patients aged 18–85 years with a first-time acute iliofemoral deep-vein thrombosis and symptoms for no more than 14 days were randomly assigned (1:1) to either standard treatment with additional ultrasound-accelerated catheter-directed thrombolysis or standard treatment alone. Randomisation was done with a web-based automatic programme and a random varying block size (2–12), stratified by age and centre. Standard treatment included anticoagulant therapy, compression therapy (knee-high elastic compression stockings; 30–40 mmHg), and early ambulation. Additional ultrasound-accelerated catheter-directed thrombolysis was done with urokinase with a starting bolus of 250 000 international units (IU) in 10 mL NaCl followed by a continuous dose of 100 000 IU/h for a maximum of 96 h through the Ekos Endowave-system. Adjunctive percutaneous transluminal angioplasty, thrombosuction, or stenting was performed at the discretion of the physician who performed the intervention. The primary outcome was the proportion of patients with post-thrombotic syndrome at 12 months diagnosed according to the original Villalta criteria—a Villalta-score of at least 5 on two consecutive occasions at least 3 months apart or the occurrence of venous ulceration—and was assessed in a modified intention-to-treat population of all randomly assigned patients who passed screening and started treatment. The safety analysis was assessed in the same modified intention-to-treat population. This study is complete and is registered at ClinicalTrials.gov, NCT00970619. Findings: Between May 28, 2010, and Sept 18, 2017, 184 patients were randomly assigned to either additional ultrasound-accelerated catheter-directed thrombolysis (n=91) or standard treatment alone (n=93). Exclusion because of screening failure or early withdrawal of informed consent resulted in 77 patients in the intervention group and 75 in the standard treatment group starting allocated treatment. Median follow-up was 12·0 months (IQR 6·0–12·0). 12-month post-thrombotic syndrome occurred in 22 (29%) patients allocated to additional treatment versus 26 (35%) patients receiving standard treatment alone (odds ratio 0·75 [95% CI 0·38 to 1·50]; p=0·42). Major bleeding occurred in four (5%) patients in the intervention group, with associated neuropraxia or the peroneal nerve in one patient, and no events in the standard treatment group. No serious adverse events occurred. None of the four deaths (one [1%] in the intervention group vs three [4%] in the standard treatment group) were treatment related. Interpretation: This study showed that additional ultrasound-accelerated catheter-directed thrombolysis does not change the risk of post-thrombotic syndrome 1 year after acute iliofemoral deep-vein thrombosis compared with standard therapy alone. Although this trial is inconclusive, the outcome suggests the possibility of a moderate beneficial effect with additional ultrasound-accelerated catheter-directed thrombolysis. Further research is therefore warranted to better understand this outcome in the context of previous trials, preferably by combining the available evidence in an individual patient data meta-analysis. Funding: The Netherlands Organisation for Health Research and Development (ZonMw), Maastricht University Medical Centre, BTG-Interventional Medicine.

Background: Thrombocytopenia in cancer patients with an indication for anticoagulation poses a unique clinical challenge. There are guidelines for the setting of venous thromboembolism but not atrial fibrillation (AF). Evidence is lacking and current practice is unclear.Objective: To identify patient and physician characteristics associated with anticoagulation management in hematological malignancy and thrombocytopenia.Methods: A clinical vignette-based experiment was designed. Eleven hematologists were interviewed, identifying 5 relevant variable categories with 2-5 options each. Thirty hypothetical vignettes were generated. Each physician received 5 vignettes and selected a management strategy (hold anticoagulation; no change; transfuse platelets; modify type/dose). The survey was distributed to hematologists and thrombosis specialists in 3 countries. Poisson regression models with cluster robust variance estimates were used to calculate relative risks for using one management option over the other, for each variable in comparison to a reference variable.Results: 168 physicians answered 774 cases and reported continuing anticoagulation for venous thromboembolism or AF in 607 (78%) cases, usually with dose reduction or platelet transfusion support. Overall, management was affected by platelet count, anticoagulation indication, time since indication, type of hematological disease and treatment, and prior major bleeding, as well as physician demographics and practice setting. The CHA(2)DS(2)-VASc score and time since AF diagnosis affected anticoagulation management in AF.Conclusion: This study indicates what the widely accepted management strategies are. These strategies, and possibly others, should be assessed prospectively to ascertain effectiveness. The decision process is intricate and compatible with current venous thromboembolism guidelines.

Purpose To determine the effect of revascularisation for peripheral arterial disease (PAD) on QoL in the first and second year following diagnosis, to compare the effect depicted by Short Form Six Dimensions (SF-6D) and EuroQoL five Dimensions (EQ-5D) utilities, and Visual Analogue Scale (VAS) scores and to analyse heterogeneity in treatment response.Methods Longitudinal data from 229 PAD patients were obtained in an observational study in southern Netherlands. Utility scores were calculated with the international (SF-6D) and Dutch (EQ-5D) tariffs. We analysed treatment effect at years 1 and 2 through propensity score-matched ANCOVAs. Thereby, we estimated the marginal means (EMMs) of revascularisation and conservative treatment, and identified covariates of revascularisation effect.Results A year after diagnosis, 70 patients had been revascularised; the EMMs of revascularisation were 0.038, 0.077 and 0.019 for SF-6D, EQ-5D and VAS, respectively (always in this order). For conservative treatment these were -0.017, 0.038 and 0.021. At 2-year follow-up, the EMMs of revascularisation were 0.015, 0.077 and 0.027, for conservative treatment these were -0.020, 0.013 and -0.004. Baseline QoL (and rest pain in year 2) were covariates of treatment effect.Conclusions We measured positive effects of revascularisation and conservative treatment on QoL a year after diagnosis, the effect of revascularisation was sustained over 2 years. The magnitude of effect varied between the metrics and was largest for the EQ-5D, which may be most suitable for QoL measurement in PAD patients. Baseline QoL influenced revascularisation effect, in clinical practice this may inform expected QoL gain in individual patients.

Background: Inflammation and hypercoagulability play a pivotal role in venous thromboembolism and atherothrombosis. Since venous thrombosis increases the risk of atherothrombotic events and vice versa, common mechanisms may be involved.Objectives: To elucidate the role of neutrophils and coagulation in the occurrence of atherothrombotic events in patients with a history of deep vein thrombosis (DVT or peripheral artery disease (PAD).Materials and Methods: We studied 115 patients from two cohorts (75 DVT, 40 PAD). From those with PAD, 20 patients had progressive disease; from those with DVT, 25 patients had a recurrent DVT and 25 suffered from post thrombotic syndrome (PTS); patients were age and sex matched to DVT and PAD patients without events. Markers of neutrophil recruitment (p-selectin) and activation [nucleosomes, human neutrophil elastase- alpha 1anti-trypsin (HNE-AT)], an anti-inflammatory marker (Lipoxin A4) and a clotting activity marker (d-dimer), were measured with ELISA. Coagulation potential was analyzed by thrombin generation (CAT method).Results: Higher nucleosome levels were found in DVT patients [11.3 U/mL (7.4-17.7)] compared to PAD patients [7.1 U/mL (5.1-13.8)], lower HNE-AT levels were found in DVT patients [33.4 ng/mL (23.5-40.5)] in comparison to PAD patients [158 ng/mL (88.1-283)]. No difference in nucleosome levels was found between DVT patients with cardiovascular (CV) events [12.6 U/mL (8.2-16.1)], and PAD patients with CV events [6.9 U/mL (4.9-11.2)]. Lipoxin A4 levels appeared to be significantly lower in DVT [2.4 ng/mL (1.7-4.8)] vs. PAD [35.6 ng/mL (16.6-80.1)], with similar results in DVT patients with CV events vs. PAD patients with CV events. Thrombin generation showed higher ETP [160.4% (141.1-215.4)], and peak height [292.1% (177.9-330)] values in DVT patients. D-dimer levels were significantly lower in the DVT cohort [330 ng/mL (220-550)] compared to the PAD cohort [550 ng/mL (369-959)].Conclusion: In DVT patients, neutrophil activity does not appear to be an important driver of CV events. Although neutrophil activity is more pronounced in PAD, its effect is partly dampened by Lipoxin A4. Moreover, no associations were found between NET products and coagulation activity, suggesting that neutrophil activation does not play a pivotal role in the risk of thrombosis in either DVT or PAD.

Compression therapy, prescribed as elastic compression stockings, is the cornerstone in the management of post-thrombotic syndrome. The effectiveness of elastic compression stockings has recently been called into question in a large randomized placebo-controlled trial. The findings however may be less contradictory than assumed and presented. The mechanistic substrate for the effectiveness of compression therapy is based on its ability to counteract venous hypertension, which is a central aspect in the pathophysiology of post-thrombotic syndrome. Nevertheless, despite elastic compression stockings a significant percentage (20–50%) of patients develops post-thrombotic syndrome, suggesting that there are other factors to be considered next to compression. Every patient has an individual baseline risk value, constituted of non-modifiable and modifiable risk factors (i.e. age, sex, bodyweight etcetera). Straining patients at risk is therefore crucial. Exploring additional or alternative forms of therapy is desirable as well since these are in addition to the risk factors, costs aspects and quality of life, puzzle pieces in the management of post-thrombotic syndrome, which once pieced together enables multifactorial yet individualized therapy.

Aim: To compare health-related quality of life (HRQoL) descriptions and utility scores in newly diagnosed peripheral arterial disease (PAD) patients, using two most widely used instruments, EuroQol 5D (EQ-5D) and Medical Outcome Study 36-item Short-Form Health Status Survey (SF-36). Methods: Patients’ self-assessment of HRQoL was measured by the Dutch versions of the EQ-5D and SF-36 in the 204 patients. Results: Mean utility scores ranged from 0.675 for Short-Form Six-Dimension, 0.648 for the EQ-5D UK tariff and 0.715 for the Dutch EQ-5D tariff. A moderate correlation between the utility scores was found due to different valuation techniques of these instruments. Conclusion: Both instruments have clinical validity for use in the PAD and can be used alongside each other to provide a holistic assessment of the HRQoL. Before using these two instruments interchangeably for utility score calculations and healthcare resource allocation, a thorough sensitivity analysis is necessary to explore the robustness of the value argument based on these utility scores.

SummaryPost-thrombotic syndrome (PTS) is a common complication of deepvein thrombosis (DVT). Poor quality treatment with vitamin K antagonists (VKA) is a risk factor for PTS. We hypothesised that treatment with the direct oral anticoagulant (DOAC) rivaroxaban may lower PTS incidence as compared to enoxaparin/VKA, as DOACs have a more stable pharmacologic profile than VKA. We performed a post-hoc subgroup analysis of the Einstein DVT trial (n=3449). Kaplan-Meier survival analysis was performed to compare the cumulative incidence of PTS between the rivaroxaban and enoxaparin/VKA groups. Hazard ratios (HR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards models. We included 336 patients with a mean age of 58 ± 16 years and a median follow-up after index DVT of 57 months (interquartile range 48–64). Of these, 162 (48 %) had been treated with rivaroxaban and 174 (52 %) with enoxaparin/VKA. The cumulative PTS incidence at 60 months follow-up was 29 % in the rivaroxaban group and 40 % in the enoxaparin/VKA group. After adjusting for age, gender, body mass index, previous VTE, ipsilateral recurrent DVT, extent of DVT, idiopathic DVT, duration of anticoagulant treatment, compliance to assigned study medication, elastic compression stocking use and active malignancy, the HR of PTS development for rivaroxaban was 0.76 (95 % CI: 0.51–1.13). In conclusion, treatment of acute DVT with rivaroxaban was associated with a numerically lower but statistically non-significant risk of PTS compared to enoxaparin/VKA treatment. The potential effect on reducing PTS deserves evaluation in a large randomised trial.Supplementary Material to this article is available online at www.thrombosis-online.com.

Introduction Venous thromboembolism (VTE) is an underestimated health problem. The administration of low molecular weight heparins (LMWH) to the appropriate patients dramatically decreases VTE incidence. Clinical decision support (CDS) might contribute to thrombosis prophylaxis guideline adherence. Methods A computerized integrated risk score program was used to estimate VTE and bleeding risk of nonsurgical patients. A VTE risk score of ≥ 4 resulted in an advice to administer LMWH. We selected 64 medical patients before the introduction of CDS (T0) and 64 patients after the introduction (T1). We compared guideline compliance between these groups using chi2 tests. Results No difference between groups was found; Adherence to the guidelines at T0 was 59.4%, the same percentage of 59.4% was found at T1. To evaluate the effect of the introduction of CDS in terms of under and overtreatment we compared the prevalence of over and under treatment at T1 and T0. The OR for receiving under treatment at T1 compared to T0 is 0.48 (95% CI: 0.18-1.30), p = 0.14. The OR for overtreatment at T1 compared to T0 is 1.66 (95% CI: 0.74-3.73), p = 0.22 Conclusion We found no improvement in guideline adherence towards anti thrombotic prophylaxis in medical patients after the introduction of CDS in this pilot study. There was however a non-significant shift towards over treatment. Possible explanations for these results are the increased awareness of the risk for thromboembolism induced by the study, suboptimal use of CDS and deviation from CDS advice caused by patient’s preferences.

Objective: Point-of-care (POC) D-dimer tests have been developed to exclude deep venous thrombosis quickly and on the spot, but are known to have lower sensitivity compared with laboratory-based tests. Their cost-effectiveness is still unknown. Methods: We updated and extended a previously published Markov model to assess the cost-effectiveness of POC D-dimer tests (Simplify', Cardiac', Triage' and Nycocard') compared with a laboratory-based latex assay to diagnose deep venous thrombosis in primary care. Results: The Laboratory' strategy resulted in 6.986 quality-adjusted life years at the cost of Euro8354 per patient. All POC D-dimer tests resulted in health outcomes similar to the Laboratory' strategy. The Simplify' strategy maximized cost savings (-Euro155 [95% CI: -Euro246 to -Euro83]). Conclusions: POC D-dimer tests yield similar health outcomes as laboratory-based testing procedures but can be performed more easily and at lower costs. Therefore, these tests are an alternative to laboratory-based testing and might be considered for exclusion of deep venous thrombosis in primary care.

Until recently, vitamin K antagonists (VKAs) were the mainstay of oral anticoagulant treatment with bleeding as the most prevalent adverse effect. One to four percent of patients experience major bleeding episodes, while clinically relevant bleeding occurs in up to 20%. At this moment no laboratory assays are available to identify patients at risk for bleeding. With this study we aimed to investigate whether thrombin generation tests might identify a bleeding risk in patients taking VKAs. This prospective cohort study included 129 patients taking VKAs for more than three months. Calibrated automated thrombinography (CAT) was performed in whole blood, platelet rich and platelet poor plasma. Hematocrit, hemoglobin concentrations and the International Normalized Ratio (INR) were defined and coagulation factor levels were measured. Forty clinically relevant bleeding episodes were registered in 26 patients during follow-up. No differences were found in plasma CAT parameters or INR values. Bleeding was not associated with age, sex, hematocrit, hemoglobin levels or coagulation factor levels. In whole blood a significantly lower endogenous thrombin potential (ETP) and peak were found in patients with bleeding (median ETP: 182.5 versus 256.2 nM. min, p = 0.002; peak: 23.9 versus 39.1 nM, p = 0.029). Additionally, the area under the receiver operating curve (AUC ROC) was significantly associated with bleeding (ETP: 0.700, p = 0.002; peak: 0.642, p = 0.029). HAS-BLED scores were also significantly higher in bleeding patients (3 versus 2, p = 0.003), with an AUC ROC 0.682 (p = 0.004). In conclusion, bleeding in patients taking VKAs is associated with a decreased whole blood ETP and peak as well as with an increased HAS-BLED score.

Aim: The objective of this study was to explore the cost–effectiveness of D-dimer biomarker and the societal value (headroom) of a hypothetical perfect biomarker for risk assessment and subsequent treatment stratification of prophylactic treatment for peripheral arterial disease (PAD). Patients & methods: Decision analytic modeling. Results: Use of the D-dimer biomarker to prescribe oral anticoagulants in the high-risk subset of patients is a cost-effective healthcare intervention. The headroom (societal willingness to pay multiplied by incremental quality-adjusted life years) available for the hypothetical perfect biomarker amounted to €83,877. Conclusion: D-dimer-based PAD risk assessment and treatment tailoring is cost effective. Identification of high-risk PAD patients and prescription of oral anticoagulants could potentially save substantial costs and improve chances of survival for high-risk PAD patients. However, further research of risk stratifying biomarkers test accuracy is needed to support and strengthen the results of this modeling study.

Continuing treatment for two years looks beneficial for those who can Until recently, the effectiveness of elastic compression stockings for the prevention of post-thrombotic syndrome following deep venous thrombosis (DVT) was considered irrefutable. Compression stockings had been embedded in daily practice and in guidelines,1 2 at least in Europe, since two randomised clinical trials showed that compression reduced the incidence of post-thrombotic syndrome by more than 20%.1 2 The results of the SOX trial, published in 2014, challenged this dogma, suggesting that elastic compression did not prevent post-thrombotic syndrome.3 Although the trial was hampered by a lack of adherence to treatment, treating clinicians readily accepted the negative outcome. Since then, guidelines have been updated and compression stockings devalued and even discouraged.4 In a linked paper (doi:10.1136/bmj.i2691), Mol and colleagues report the results of the OCTAVIA trial, a non-inferiority …

a Maastricht University Medical Center, Laboratory for Clinical Thrombosis and Hemostasis, Cardiovascular Research Institute Maastricht (CARIM), Netherlands b Thrombosis Center, USA c McMaster University and Thrombosis and Atherosclerosis Research Institute, Canada d Vanderbilt University, Department of Pathology, Microbiology and Immunology, Nashville, USA e University of Groningen, University Medical Center Groningen, Department of Hematology, Netherlands f University of Leeds, Division of Cardiovascular and Diabetes Research, The LIGHT Labs, Leeds, UK g University of Amsterdam, Academic Medical Center, Department of Vascular Medicine, Netherlands h Erasmus University Medical Center, Rotterdam, Department of Hematology, Netherlands

Introduction Post-thrombotic syndrome (PTS) is a serious complication of deep vein thrombosis (DVT) of the leg that affects 20–50% of patients. Once a patient experiences PTS there is no treatment that effectively reduces the debilitating complaints. Two randomised controlled trials showed that elastic compression stocking (ECS) therapy after DVT for 24 months can reduce the incidence of PTS by 50%. However, it is unclear whether all patients benefit to the same extent from ECS therapy or what the optimal duration of therapy for individual patients should be. ECS therapy is costly, inconvenient, demanding and sometimes even debilitating. Tailoring therapy to individual needs could save substantial costs. The objective of the IDEAL DVT study, therefore, is to evaluate whether tailoring the duration of ECS therapy on signs and symptoms of the individual patient is a safe and effective method to prevent PTS, compared with standard ECS therapy. Methods and analysis A multicentre, single-blinded, allocation concealed, randomised, non-inferiority trial. A total of 864 consecutive patients with acute objectively documented proximal DVT of the leg are randomised to either standard duration of 24 months or tailored duration of ECS therapy following an initial therapeutic period of 6 months. Signs and symptoms of PTS are recorded at regular clinic visits. Furthermore, quality of life, costs, patient preferences and compliance are measured. The primary outcome is the proportion of patients with PTS at 24 months. Ethics and dissemination Based on current knowledge the standard application of ECS therapy is questioned. The IDEAL DVT study will address the central questions that remain unanswered: Which individual patients benefit from ECS therapy and what is the optimal individual treatment duration? Primary ethics approval was received from the Maastricht University Medical Centre. Results Results of the study will be disseminated via peer-reviewed publications and presentations at scientific conferences. Trial registration number NCT01429714 and NTR 2597.

The blood coagulation system is a key survival mechanism that has developed to protect man against lethal bleeding. A second function of blood coagulation is its close interaction with immunity. The immune-mediated coagulation responses may broadly be regarded as an element of response to injury. Pathological coagulation responses, including thromboembolism and disseminated intravascular coagulation (DIC), could therefore be regarded as excessive immune responses to a vessel wall injury. Virchow's triad, which comprises changes in the components of the blood, the state of the vessel wall, and the blood flow, was originally proposed for venous thrombosis. However, lately it appears that the same principles can be applied to arterial thrombosis and even DIC. It has even been postulated that all forms of thrombosis may be part of a continuous spectrum of the same disease. Over the past few years, an accumulation of evidence has shown that the etiopathogenetic mechanisms behind venous and arterial thrombosis are quite similar. The traditional elements of Virchow's triad are found to apply to both arterial and venous thrombosis. Yet, nowadays more emphasis is placed on the vessel wall and vascular bed specificity and the interaction with inflammation and hypercoagulability. This narrative review will discuss recent advances in research on the possible interactions between coagulation, the vascular endothelium, and atherosclerosis as well as the consequences of such interactions for venous and arterial thrombosis.