Publications by authors named "Arina J Ten Cate-Hoek"

62 Publications

Using the Functional Resonance Analysis Method to explore how elastic compression therapy is organised and could be improved from a multistakeholder perspective.

BMJ Open 2021 10 12;11(10):e048331. Epub 2021 Oct 12.

Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.

Objectives: Elastic 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.

Design: Thirty 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.

Setting: Two regions in the Netherlands, region Limburg and region North-Holland, including an academic hospital and a general hospital and their catchment region.

Participants: The 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.

Results: Two 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.

Conclusions: This 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.
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http://dx.doi.org/10.1136/bmjopen-2020-048331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513256PMC
October 2021

A known unknown? Pharmacological prevention of venous thromboembolism in nursing home residents.

J Am Geriatr Soc 2021 Nov 23;69(11):3338-3343. Epub 2021 Aug 23.

Department of Internal Medicine, Section Vascular Medicine and Thrombosis Expert Center, Maastricht University Medical Center+, Maastricht, The Netherlands.

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http://dx.doi.org/10.1111/jgs.17422DOI Listing
November 2021

Exploring the Feasibility of Comprehensive Uncertainty Assessment in Health Economic Modeling: A Case Study.

Value Health 2021 Jul 31;24(7):983-994. Epub 2021 Mar 31.

Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.jval.2021.01.004DOI Listing
July 2021

CAVA (Ultrasound-Accelerated Catheter-Directed Thrombolysis on Preventing Post-Thrombotic Syndrome) Trial: Long-Term Follow-Up Results.

J Am Heart Assoc 2021 06 25;10(11):e018973. Epub 2021 May 25.

CARIM Cardiovascular Research Institute MaastrichtSchool for Cardiovascular DiseasesMaastricht University Medical Centre Maastricht the Netherlands.

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 [=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 [=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.
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http://dx.doi.org/10.1161/JAHA.120.018973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483549PMC
June 2021

Predicting Recurrent Venous Thromboembolism in Patients With Deep-Vein Thrombosis: Development and Internal Validation of a Potential New Prediction Model (Continu-8).

Front Cardiovasc Med 2021 6;8:655226. Epub 2021 Apr 6.

Laboratory of Clinical Thrombosis and Haemostasis, Thrombosis Expertise Center, Cardiovascular Research Institute, Maastricht University Medical Center, Maastricht, Netherlands.

Previous prediction models for recurrent thromboembolism (VTE) are often complicated to apply and have not been implemented widely. 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. 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. 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). 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.
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http://dx.doi.org/10.3389/fcvm.2021.655226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055939PMC
April 2021

Leukocyte gene expression in post-thrombotic syndrome.

Thromb Res 2021 06 8;202:40-42. Epub 2021 Mar 8.

Thrombosis Expertise Center, Heart+Vascular Center, Maastricht University Medical Center (MUMC), Maastricht, the Netherlands; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.

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http://dx.doi.org/10.1016/j.thromres.2021.03.007DOI Listing
June 2021

Postinterventional antithrombotic management after venous stenting of the iliofemoral tract in acute and chronic thrombosis: A systematic review.

J Thromb Haemost 2021 03 5;19(3):753-796. Epub 2021 Jan 5.

School for Cardiovascular Diseases, CARIM, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.

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.
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http://dx.doi.org/10.1111/jth.15197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986750PMC
March 2021

Prevalence of venous obstructions in (recurrent) venous thromboembolism: a case-control study.

Thromb J 2020 16;18:23. Epub 2020 Sep 16.

CARIM, Cardiovascular Research Institute Maastricht, School for Cardiovascular Diseases, Maastricht University Medical Centre, P.O. Box 616, Maastricht, 6200 MD the Netherlands.

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,  = 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 ( = 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,  = 0.752). If venous obstruction was present, it was mainly located in the common iliac vein ( = 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 ( = 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,  = 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.
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http://dx.doi.org/10.1186/s12959-020-00238-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493864PMC
September 2020

Effect of switching from acenocoumarol to phenprocoumon on time in therapeutic range and INR variability: A cohort study.

PLoS One 2020 10;15(7):e0235639. Epub 2020 Jul 10.

Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Background: Treatment with vitamin K antagonists (VKA) requires a high proportion of time in the therapeutic range (TTR) and a low international normalised ratio (INR) variability to be maximally safe and effective. Switching from short-acting acenocoumarol to long-acting phenprocoumon could improve VKA control.

Aims: We assessed whether switching from acenocoumarol to phenprocoumon improves the time in the therapeutic range (TTR) and INR variability.

Methods And Results: In a retrospective cohort with data on 236,957 patients-years of VKA management from two first-line anticoagulation clinics in the Netherlands, we identified 124 patients in target range 2-3, 269 patients in target range 2-3.5 and 98 patients in target range 2.5-3.5 who switched from acenocoumarol to phenprocoumon. They were matched in a 1:2 ratio to non-switching controls using propensity score matching. Over the first 180 days after a switch, switchers' TTR declined 5 (95% CI 1 to 10), 10 (95% CI 7 to 13) and 5 (95% CI 0 to 11) percentage points relative to non-switchers, in target ranges 2-3, 2-3.5 and 2.5-3.5. Anticoagulation was more often supra-therapeutic in switchers, and switchers had a higher INR variability. In the following 180 days, TTR in switchers became 1 (95% CI -4 to 6), 4 (95% CI 0 to 7) and 6 (95% CI 1 to 12) percentage points better than in non-switchers. Switchers' INRs were much more stable than non-switchers'.

Conclusion: Eventually, a switch from acenocoumarol to phenprocoumon leads to a higher TTR and a lower INR variability. However, this is preceded by a transition period with opposite effects. An improved conversion algorithm could possibly shorten the transition period. Until then, physicians and patients should decide whether switching is worth the increased risk during the transition phase.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235639PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351201PMC
September 2020

Mortality and the Use of Antithrombotic Therapies Among Nursing Home Residents with COVID-19.

J Am Geriatr Soc 2020 Aug 21;68(8):1647-1652. Epub 2020 Jul 21.

Department of Internal Medicine, Division of General Internal Medicine, Section Geriatric Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands.

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.
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http://dx.doi.org/10.1111/jgs.16664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361386PMC
August 2020

Association of Successful Ultrasound-Accelerated Catheter-Directed Thrombolysis with Postthrombotic Syndrome: A Post Hoc Analysis of the CAVA Trial.

Thromb Haemost 2020 Aug 30;120(8):1188-1199. Epub 2020 Jun 30.

Cardiovascular Research Institute Maastricht (CARIM), School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands.

Background:  The CAVA trial did not show the anticipated risk reduction for postthrombotic syndrome (PTS) after thrombus removal via additional ultrasound-accelerated catheter-directed thrombolysis (UACDT) in patients with acute iliofemoral deep vein thrombosis (IFDVT). Difficulties in achieving an effective degree of recanalization through thrombolysis may have influenced outcomes. We therefore assessed whether successful UACDT (restored patency ≥ 90%) did reduce the development of PTS.

Methods:  This CAVA trial post hoc analysis compared the proportion of PTS at 1-year follow-up between patients with successful UACDT and patients that received standard treatment only. In addition, clinical impact as well as determinants of successful thrombolysis were explored.

Results:  UACDT was initiated in 77 (50.7%) patients and considered successful in 41 (53.2%, interrater agreement  = 0.7, 95% confidence interval 0.47-0.83). PTS developed in 15/41 (36.6%) patients in the successful UACDT group versus 33/75 (44.0%) controls ( = 0.44). In this comparison, successful UACDT was associated with lower Venous Clinical Severity Score (3.50 ± 2.57 vs. 4.82 ± 2.74,  = 0.02) and higher EuroQOL-5D (EQ-5D) scores (40.2 ± 36.4 vs. 23.4 ± 34.4,  = 0.01). Compared with unsuccessful UACDT, successful UACDT was associated with a shorter symptom duration at inclusion ( = 0.05), and higher rates of performed adjunctive procedures ( < 0.001) and stent placement ( < 0.001).

Conclusion:  Successful UACDT was not associated with a reduced proportion of PTS 1 year after acute IFDVT compared with patients receiving standard treatment alone. There was, however, a significant reduction in symptom severity and improvement of generic quality of life according to the EQ-5D. Better patient selection and optimization of treatment protocols are needed to assess the full potential of UACDT for the prevention of PTS.

Trial Registration Number:  ClinicalTrials.gov number, NCT00970619.
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http://dx.doi.org/10.1055/s-0040-1713171DOI Listing
August 2020

Quality of anticoagulant therapy and the incidence of in-stent thrombosis after venous stenting.

Res Pract Thromb Haemost 2020 May 8;4(4):594-603. Epub 2020 Apr 8.

CARIM School for Cardiovascular Diseases Cardiovascular Research Institute Maastricht Maastricht University Medical Centre Maastricht the Netherlands.

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 < 2.0. In-stent thrombosis was assessed by the use of duplex ultrasound. Survival analysis (Kaplan-Meier curves, Cox regression) was used to analyze the data.

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 < 2.0 of 11.6% (±12.0). Overall, a TTR < 49.9% was associated with an increased risk of in-stent thrombosis. The multivariable adjusted analysis showed a hazard ratio (HR) of 0.96 (95% confidence interval [CI], 0.92-0.99;  = .02) per 1% increase in TTR. The proportion of INR values < 2.0 had no significant association with the occurrence of in-stent thrombosis: HR 0.98 (95% CI, 0.91-1.06;  = .66).

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.
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http://dx.doi.org/10.1002/rth2.12330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292674PMC
May 2020

Diagnosing deep vein thrombosis in cancer patients with suspected symptoms: An individual participant data meta-analysis.

J Thromb Haemost 2020 09 8;18(9):2245-2252. Epub 2020 Jul 8.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

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 <2%.

Conclusions: Likely because of the high prevalence of DVT, clinical models followed by D-dimer testing fail to rule out DVT efficiently in cancer patients suspected of DVT. Direct referral for compression ultrasonography appears to be the preferred approach for diagnosis of suspected DVT in cancer patients.
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http://dx.doi.org/10.1111/jth.14900DOI Listing
September 2020

Thrombo-Inflammation in Cardiovascular Disease: An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis.

Thromb Haemost 2020 Apr 14;120(4):538-564. Epub 2020 Apr 14.

Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Haemostasis Research Unit, University College London, London, United Kingdom.

Thrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.
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http://dx.doi.org/10.1055/s-0040-1708035DOI Listing
April 2020

Anticoagulation in thrombocytopenic patients with hematological malignancy: A multinational clinical vignette-based experiment.

Eur J Intern Med 2020 07 13;77:86-96. Epub 2020 Mar 13.

Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Thrombosis Expert Center, Maastricht University Medical Center, Maastricht, the Netherlands.

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 CHADS-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.
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http://dx.doi.org/10.1016/j.ejim.2020.03.005DOI Listing
July 2020

Catheter interventions: an unresolved clinical controversy - Authors' reply.

Lancet Haematol 2020 03;7(3):e190

Heart and Vascular Centre and Thrombosis Expertise Centre, Maastricht University Medical Centre, Maastricht, 6202 AZ Maastricht, Netherlands.

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http://dx.doi.org/10.1016/S2352-3026(20)30032-6DOI Listing
March 2020

Ultrasound-accelerated catheter-directed thrombolysis versus anticoagulation for the prevention of post-thrombotic syndrome (CAVA): a single-blind, multicentre, randomised trial.

Lancet Haematol 2020 Jan 27;7(1):e40-e49. Epub 2019 Nov 27.

Department of Vascular Surgery, Maastricht University Medical Centre, Maastricht, Netherlands; Department of Vascular Surgery, Aachen University Medical Centre, Aachen, Germany.

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.
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http://dx.doi.org/10.1016/S2352-3026(19)30209-1DOI Listing
January 2020

The daily practice of direct oral anticoagulant use in patients with atrial fibrillation; an observational cohort study.

PLoS One 2019 6;14(6):e0217302. Epub 2019 Jun 6.

Thrombosis Expert Center Maastricht and Laboratory for Clinical Thrombosis and Hemostasis, Maastricht, the Netherlands.

Background: Direct oral anticoagulants (DOACs) are administered in fixed doses without monitoring. There is still little published data on the impact of the absence of monitoring on adherence to medication and stability of DOAC plasma levels over time.

Objectives: To explore adherence and stability of DOAC plasma levels over time in patients with atrial fibrillation (NVAF) recently started on DOAC therapy.

Patients And Methods: A prospective observational cohort study with structured follow up including assessment of adherence to medication, plasma levels at baseline, 3,6 and 12 months and adverse events.

Results: We included 164 patients; 89% were previous users of a vitamin K antagonist (VKA). One-year adherence was reasonably good: Morisky adherence measurement scores of 6-8 in 92%. The majority of DOAC plasma levels were within reported on-therapy ranges; dabigatran (median 104.4 ng/ml, IQR 110.2), rivaroxaban (median 185.2 ng/ml, IQR 216.1) and on average levels were not different for full and adjusted doses. There was significant variation between patients, but no significant differences over time within individuals. A substantial proportion of patients starting in the upper-or lower 20th percentiles remained there during the entire follow up. Seventeen bleedings (16 minor, 1 major) were reported, no ischemic events and bleeding or thrombotic events were not associated with DOAC plasma levels.

Conclusions: Adherence was reasonably good in the majority of patients. Our data confirm the stability of DOAC plasma levels over time. Knowledge of such data may, in the individual patient, contribute to optimal drug and dose selection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217302PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554016PMC
February 2020

Searching for a Common Thrombo-Inflammatory Basis in Patients With Deep Vein Thrombosis or Peripheral Artery Disease.

Front Cardiovasc Med 2019 2;6:33. Epub 2019 Apr 2.

Laboratory for Clinical Thrombosis and Hemostasis, Maastricht, Netherlands.

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. 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). 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- α1anti-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). 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)]. 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.
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http://dx.doi.org/10.3389/fcvm.2019.00033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454153PMC
April 2019

Comparison of three generic quality-of-life metrics in peripheral arterial disease patients undergoing conservative and invasive treatments.

Qual Life Res 2019 Aug 30;28(8):2257-2279. Epub 2019 Mar 30.

Department of Clinical Epidemiology and Medical Technology Assessment (KEMTA), Maastricht University Medical Centre +, Maastricht, The Netherlands.

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.
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http://dx.doi.org/10.1007/s11136-019-02166-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620242PMC
August 2019

Managing Anti-Platelet Therapy in Thrombocytopaenic Patients with Haematological Malignancy: A Multinational Clinical Vignette-Based Experiment.

Thromb Haemost 2019 Jan 31;119(1):163-174. Epub 2018 Dec 31.

Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.

Data on anti-platelet therapy (APT) for prevention of atherothrombotic events in thrombocytopaenic cancer patients is lacking. We aimed to identify patient and physician characteristics associated with APT management in thrombocytopaenic patients with haematological malignancy. A clinical vignette-based experiment was designed. Eleven haematologists were interviewed, identifying five variable categories. Next, 18 hypothetical vignettes were generated. Each physician received three vignettes and chose to: hold all APT; continue APT without platelet transfusion support; or continue APT with platelet transfusion support. The survey was distributed to haematologists and thrombosis specialists in three countries. Multivariate cluster robust Poisson regression models were used to calculate relative risks (RRs) of using one management option (over the other) for each variable in comparison to a reference variable. A total of 145 physicians answered 434 cases. Clinicians were more likely to hold APT in case of 20,000/µL platelets (vs. 40,000/µL; RR for continuing: 0.82 [95% confidence interval: 0.75-0.91]), recent major gastrointestinal bleeding (vs. none; RR 0.81 [0.72-0.92]) and when the physician worked at a university-affiliated community hospital (vs. non-academic community hospital; RR 0.84 [0.72-0.98]). Clinicians were more likely to continue APT in ST elevation myocardial infarction with dual APT (vs. unstable angina with single APT; RR 1.31 [1.18-1.45]) and when there were institutional protocols guiding management (vs. none; RR 1.15 [1.03-1.27]). When APT was continued, increased platelet transfusion targets were used in 34%. In summary, the decision process is complex and affected by multiple patient and physician characteristics. Platelet transfusions were frequently chosen to support APT, although no evidence supports this practice.
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http://dx.doi.org/10.1055/s-0038-1676520DOI Listing
January 2019

The need for a timely diagnostic workup for patients with venous leg ulcers.

J Wound Care 2018 11;27(11):758-763

Department of Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands. School for Public Health and Prim Care, Fac, Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands.

Objective: To explore the need for an extended diagnostic workup in patients with venous leg ulcers (VLUs) and to establish the prevalence of the underlying causes of VLU.

Method: This retrospective cohort study analysed data from patients with VLU. The visual analogue scale (VAS) was used for pain assessment. The ankle-brachial index (ABI) was measured to exclude patients with arterial pathology. A duplex was performed. All patients received a wound treatment plan and ambulatory compression therapy. Continuous variables were presented as mean±standard deviation (SD) or median and interquartile range (IQR). Mann-Whitney U test and Kruskal-Wallis were used. When normally distributed, an independent sample t-test was used.

Results: A total of 70 patients were recruited. Of these, 18 (25.7%) experienced a VLU once and 52 (74.3%) had a recurrent VLU. Treatment of the underlying lesions was performed in almost 30% of patients. Patients who were treated showed almost two times slower healing rates compared with those who were not treated for an underlying pathology. The mean time in patient referral exceeded two years, and patients who did not see their GP were treated by nurses who did not provide regular feedback the GP; as a result, compression therapy was not always adequate.

Conclusion: Patients with a VLU showing no signs of healing after 2 months should be referred to a dedicated wound care centre to avoid delays.
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http://dx.doi.org/10.12968/jowc.2018.27.11.758DOI Listing
November 2018

Individually shortened duration versus standard duration of elastic compression therapy for prevention of post-thrombotic syndrome: a cost-effectiveness analysis.

Lancet Haematol 2018 Nov 9;5(11):e512-e519. Epub 2018 Oct 9.

Department of Clinical Epidemiology and Medical Technology Assessment, School for Public Health and Primary Care, Maastricht University, Maastricht, Netherlands.

Background: The IDEAL DVT study showed that it was safe to shorten the duration of elastic compression therapy on an individualised basis after deep vein thrombosis for prevention of post-thrombotic syndrome. In this study, we assessed the cost-effectiveness of this strategy.

Methods: IDEAL DVT was a multicentre, randomised, non-inferiority trial that included patients with acute proximal deep vein thrombosis of the leg. After 6 months of elastic compression therapy, patients were randomly assigned (1:1) to the standard 2 years of elastic stocking compression therapy or shortened duration of compression therapy based on the patient's Villalta score. For our cost-effectiveness analysis, we assessed quality-adjusted life-years (QALYs), measured with the three-level version of EQ-5D (EQ-5D-3L; Dutch and UK tariff) and the 36-item Short Form Health Survey (SF-36), and costs in € (health-care and societal perspective) according to the intention-to-treat approach. Data were collected at 3, 6, 12, and 24 months after diagnosis of thrombosis. We calculated incremental net monetary benefit using a QALY threshold of €30 000, and obtained bootstrapped means and 95% CIs. IDEAL DVT is registered with ClinicalTrials.gov, number NCT01429714.

Findings: Between March 22, 2011, and July 1, 2015, 865 patients were enrolled in IDEAL DVT. 437 were assigned to individualised duration of elastic compression therapy and 428 to standard duration of elastic compression therapy. Nine patients were eventually excluded because of recurrent venous thromboembolism within 6 months after the first event. From a societal perspective, for every QALY lost measured with the EQ-5D Dutch tariff, cost savings were €305·992 (incremental net monetary benefit €3205, 95% CI 502-5741), and for every QALY lost based on the Short-Form Six-Dimension (SF-6D) utility score (derived from SF-36), cost savings were €6030·941 (€3540, 95% CI 1174-5953). Using the UK tariff for EQ-5D, the individualised strategy was more effective and less costly (€4071, 1452-6647). The probability that the individualised strategy was cost-effective was 99% at a threshold of €30 000 per QALY (EQ-5D Dutch tariff).

Interpretation: Individually shortened duration of elastic compression therapy was cost-effective compared with standard duration elastic compression therapy. Use of an individualised approach to elastic stocking compression therapy for the prevention of post-thrombotic syndrome after deep vein thrombosis could lead to substantial costs savings without loss in health-related quality of life.

Funding: Netherlands Organisation for Health Research and Development.
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http://dx.doi.org/10.1016/S2352-3026(18)30151-0DOI Listing
November 2018

Reduced incidence of vein occlusion and postthrombotic syndrome after immediate compression for deep vein thrombosis.

Blood 2018 11 20;132(21):2298-2304. Epub 2018 Sep 20.

Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.

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).
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http://dx.doi.org/10.1182/blood-2018-03-836783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302282PMC
November 2018

Risk factors for recurrence in deep vein thrombosis patients following a tailored anticoagulant treatment incorporating residual vein obstruction.

Res Pract Thromb Haemost 2018 Apr 3;2(2):299-309. Epub 2018 Feb 3.

Thrombosis Expertise Center and Laboratory of Clinical Thrombosis and Hemostasis, and Cardiovascular Research Institute Maastricht University Medical Center Maastricht The Netherlands.

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.
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http://dx.doi.org/10.1002/rth2.12079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055496PMC
April 2018

Prevention and treatment of the post-thrombotic syndrome.

Res Pract Thromb Haemost 2018 Apr 10;2(2):209-219. Epub 2018 Mar 10.

Heart+ and Vascular Center, Internal Medicine Cardiovascular Research Institute Maastricht University Medical Center Maastricht the Netherlands.

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.
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http://dx.doi.org/10.1002/rth2.12085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055553PMC
April 2018

Development and Validation of a Practical Two-Step Prediction Model and Clinical Risk Score for Post-Thrombotic Syndrome.

Thromb Haemost 2018 Jul 4;118(7):1242-1249. Epub 2018 Jun 4.

Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.

Background:  Post-thrombotic syndrome (PTS) is a common chronic consequence of deep vein thrombosis that affects the quality of life and is associated with substantial costs. In clinical practice, it is not possible to predict the individual patient risk. We develop and validate a practical two-step prediction tool for PTS in the acute and sub-acute phase of deep vein thrombosis.

Methods:  Multivariable regression modelling with data from two prospective cohorts in which 479 (derivation) and 1,107 (validation) consecutive patients with objectively confirmed deep vein thrombosis of the leg, from thrombosis outpatient clinic of Maastricht University Medical Centre, the Netherlands (derivation) and Padua University hospital in Italy (validation), were included. PTS was defined as a Villalta score of ≥ 5 at least 6 months after acute thrombosis.

Results:  Variables in the baseline model in the acute phase were: age, body mass index, sex, varicose veins, history of venous thrombosis, smoking status, provoked thrombosis and thrombus location. For the secondary model, the additional variable was residual vein obstruction. Optimism-corrected area under the receiver operating characteristic curves (AUCs) were 0.71 for the baseline model and 0.60 for the secondary model. Calibration plots showed well-calibrated predictions. External validation of the derived clinical risk scores was successful: AUC, 0.66 (95% confidence interval [CI], 0.63-0.70) and 0.64 (95% CI, 0.60-0.69).

Conclusion:  Individual risk for PTS in the acute phase of deep vein thrombosis can be predicted based on readily accessible baseline clinical and demographic characteristics. The individual risk in the sub-acute phase can be predicted with limited additional clinical characteristics.
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http://dx.doi.org/10.1055/s-0038-1655743DOI Listing
July 2018

Comparison of EQ-5D and SF-36 in untreated patients with symptoms of intermittent claudication.

J Comp Eff Res 2018 06 1;7(6):535-548. Epub 2018 Jun 1.

Department of Clinical Epidemiology & Medical Technology Assessment (KEMTA), Maastricht University Medical Centre, Maastricht, the Netherlands.

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.
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http://dx.doi.org/10.2217/cer-2017-0029DOI Listing
June 2018

Individualised versus standard duration of elastic compression therapy for prevention of post-thrombotic syndrome (IDEAL DVT): a multicentre, randomised, single-blind, allocation-concealed, non-inferiority trial.

Lancet Haematol 2018 Jan 5;5(1):e25-e33. Epub 2017 Dec 5.

Department of Vascular Medicine, Heart and Vascular Center, Maastricht University Medical Center, Maastricht, Netherlands; Laboratory of Clinical Thrombosis and Hemostasis, Cardio Vascular Research Institute, Maastricht University, Maastricht, Netherlands.

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
Findings: Between March 22, 2011, and July 1, 2015, we enrolled 865 patients and randomly assigned 437 to individualised duration compression stockings and 428 to standard duration. 283 (66%) of 432 patients in the intervention group were advised before 24 months to stop wearing elastic compression stockings (236 [55%] of 432 patients after 6 months, and 47 [11%] of 432 at 12 months). Post-thrombotic syndrome occurred in 125 (29%) of 432 patients receiving individualised duration of therapy and in 118 (28%) of 424 receiving standard duration of therapy (odds ratio for difference 1·06, 95% CI 0·78 to 1·44). The absolute difference was 1·1% (95% CI -5·2 to 7·3), thus meeting the non-inferiority margin. 24 patients died, 17 (4%) in the individualised treatment group and seven (2%) in the standard duration group, but no deaths were related to treatment. No serious adverse events related to the intervention occurred.

Interpretation: Individualised therapy with elastic compression stockings for the prevention of post-thrombotic syndrome was non-inferior to standard duration of therapy of 24 months. Individualising the duration is effective and could shorten the length of therapy needed, potentially enhancing patients' wellbeing.

Funding: ZonMw (Netherlands).
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http://dx.doi.org/10.1016/S2352-3026(17)30227-2DOI Listing
January 2018
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