Publications by authors named "Vincent Ten Cate"

18 Publications

  • Page 1 of 1

A targeted proteomics investigation of the obesity paradox in venous thromboembolism.

Blood Adv 2021 07;5(14):2909-2918

Preventive Cardiology and Preventive Medicine, Center for Cardiology.

The obesity paradox, the controversial finding that obesity promotes disease development but protects against sequelae in patients, has been observed in venous thromboembolism (VTE). The aim of this investigation was to identify a body mass-related proteomic signature in VTE patients and to evaluate whether this signature mediates the obesity paradox in VTE patients. Data from the Genotyping and Molecular Phenotyping in Venous ThromboEmbolism Project, a prospective cohort study of 693 VTE patients, were analyzed. A combined end point of recurrent VTE or all-cause death was used. Relative quantification of 444 proteins was performed using high-throughput targeted proteomics technology. Measurements were performed in samples collected during the acute VTE event and at 12-month follow-up. An 11-protein signature (CLEC4C, FABP4, FLT3LG, IL-17C, LEP, LYVE1, MASP1, ST2, THBS2, THBS4, TSLP) for body mass in VTE patients was identified. The signature did not significantly mediate the obesity paradox (change in hazard ratio [HR]: 0.04; likelihood ratio test of nested models = 7.7; P = .74), but its main constituent protein, leptin, was inversely associated with recurrent VTE or death (adjusted HR [95% confidence interval] per standard deviation increase: 0.66 [0.46-0.94]). This relationship was significantly (P = .007) modified by markers of leptin resistance (ie, high body mass index and high circulating matrix metalloproteinase-2 levels). Although the signature did not substantially explain the obesity paradox, leptin appears to be protective against disease recurrence and death in VTE patients. This protective effect was abrogated under conditions of leptin resistance and hence was unrelated to the obesity paradox.
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http://dx.doi.org/10.1182/bloodadvances.2020003800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341360PMC
July 2021

Protein expression profiling suggests relevance of noncanonical pathways in isolated pulmonary embolism.

Blood 2021 May;137(19):2681-2693

Preventive Cardiology and Preventive Medicine, Center for Cardiology.

Patients with isolated pulmonary embolism (PE) have a distinct clinical profile from those with deep vein thrombosis (DVT)-associated PE, with more pulmonary conditions and atherosclerosis. These findings suggest a distinct molecular pathophysiology and the potential involvement of alternative pathways in isolated PE. To test this hypothesis, data from 532 individuals from the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism Project, a multicenter prospective cohort study with extensive biobanking, were analyzed. Targeted, high-throughput proteomics, machine learning, and bioinformatic methods were applied to contrast the acute-phase plasma proteomes of isolated PE patients (n = 96) against those of patients with DVT-associated PE (n = 276) or isolated DVT (n = 160). This resulted in the identification of shared molecular processes between PE phenotypes, as well as an isolated PE-specific protein signature. Shared processes included upregulation of inflammation, response to oxidative stress, and the loss of pulmonary surfactant. The isolated PE-specific signature consisted of 5 proteins: interferon-γ, glial cell line-derived neurotrophic growth factor, polypeptide N-acetylgalactosaminyltransferase 3, peptidyl arginine deiminase type-2, and interleukin-15 receptor subunit α. These proteins were orthogonally validated using cis protein quantitative trait loci. External replication in an independent population-based cohort (n = 5778) further validated the proteomic results and showed that they were prognostic for incident primary isolated PE in individuals without history of VTE (median time to event: 2.9 years; interquartile range: 1.6-4.2 years), supporting their possible involvement in the early pathogenesis. This study has identified molecular overlaps and differences between VTE phenotypes. In particular, the results implicate noncanonical pathways more commonly associated with respiratory and atherosclerotic disease in the acute pathophysiology of isolated PE.
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http://dx.doi.org/10.1182/blood.2019004571DOI Listing
May 2021

Missing value imputation in proximity extension assay-based targeted proteomics data.

PLoS One 2020 14;15(12):e0243487. Epub 2020 Dec 14.

Institute of Organismic and Molecular Evolution, Johannes Gutenberg University Mainz, Mainz, Germany.

Targeted proteomics utilizing antibody-based proximity extension assays provides sensitive and highly specific quantifications of plasma protein levels. Multivariate analysis of this data is hampered by frequent missing values (random or left censored), calling for imputation approaches. While appropriate missing-value imputation methods exist, benchmarks of their performance in targeted proteomics data are lacking. Here, we assessed the performance of two methods for imputation of values missing completely at random, the previously top-benchmarked 'missForest' and the recently published 'GSimp' method. Evaluation was accomplished by comparing imputed with remeasured relative concentrations of 91 inflammation related circulating proteins in 86 samples from a cohort of 645 patients with venous thromboembolism. The median Pearson correlation between imputed and remeasured protein expression values was 69.0% for missForest and 71.6% for GSimp (p = 5.8e-4). Imputation with missForest resulted in stronger reduction of variance compared to GSimp (median relative variance of 25.3% vs. 68.6%, p = 2.4e-16) and undesired larger bias in downstream analyses. Irrespective of the imputation method used, the 91 imputed proteins revealed large variations in imputation accuracy, driven by differences in signal to noise ratio and information overlap between proteins. In summary, GSimp outperformed missForest, while both methods show good overall imputation accuracy with large variations between proteins.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243487PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735586PMC
January 2021

Telemedicine-Based Specialized Care Improves the Outcome of Anticoagulated Individuals with Venous Thromboembolism-Results from the thrombEVAL Study.

J Clin Med 2020 Oct 13;9(10). Epub 2020 Oct 13.

Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.

Venous thromboembolism (VTE) is a life-threatening disease with risk of recurrence. Oral anticoagulation (OAC) with vitamin K antagonists (VKA) is effective to prevent thromboembolic recurrence. We aimed to investigate the quality of OAC of VTE patients in regular medical care (RMC) compared to a telemedicine-based coagulation service (CS). The thrombEVAL study (NCT01809015) is a prospective, multi-center study to investigate OAC treatment (recruitment: January 2011-March 2013). Patients were evaluated using clinical visits, computer-assisted personal interviews, self-reported data and laboratory measurements according to standard operating procedures. Overall, 360 patients with VTE from RMC and 254 from CS were included. Time in therapeutic range (TTR) was higher in CS compared to RMC (76.9% (interquartile range [IQR] 63.2-87.1%) vs. 69.5% (52.3-85.6%), < 0.001). Crude rate of thromboembolic events (rate ratio [RR] 11.33 (95% confidence interval [CI] 1.85-465.26), = 0.0015), clinically relevant bleeding (RR 6.80 (2.52-25.76), < 0.001), hospitalizations (RR 2.54 (1.94-3.39), < 0.001) and mortality under OAC (RR 5.89 (2.40-18.75), < 0.001) were consistently higher in RMC compared with CS. Patients in RMC had higher risk for primary outcome (clinically relevant bleedings, thromboembolic events and mortality, hazard ratio [HR] 5.39 (95%CI 2.81-10.33), < 0.0001), mortality (HR 5.54 (2.22-13.84), = 0.00025), thromboembolic events (HR 6.41 (1.51-27.24), = 0.012), clinically relevant bleeding (HR 5.31 (1.89-14.89), = 0.0015) and hospitalization (HR 1.84 (1.34-2.55), = 0.0002). Benefits of CS care were still observed after adjusting for comorbidities and TTR. In conclusion, anticoagulation quality and outcome of VTE patients undergoing VKA treatment was significantly better in CS than in RMC. Patients treated in CS had lower rates of adverse events, hospitalizations and lower mortality. CS was prognostically relevant, beyond providing advantages of improved international ratio (INR) monitoring.
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http://dx.doi.org/10.3390/jcm9103281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602093PMC
October 2020

Comprehensive platelet phenotyping supports the role of platelets in the pathogenesis of acute venous thromboembolism - results from clinical observation studies.

EBioMedicine 2020 Oct 10;60:102978. Epub 2020 Sep 10.

Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Germany; Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Germany; DZHK (German Center for Cardiovascular Research), Partner Site RhineMain, Mainz, Germany.

Background: The pathogenesis of arterial and venous thrombosis is in large part interlaced. How much platelet phenotype relates to acute venous thromboembolism (VTE) independent of the underlying cardiovascular profile is presently poorly investigated.

Methods: Platelet count and mean platelet volume (MPV), platelet aggregation in whole blood and platelet rich plasma (PRP), platelet-dependent thrombin generation (TG) and platelet surface activation markers were measured under standardized conditions. Machine learning was applied to identify the most relevant characteristics associated with VTE from a large array (N = 58) of clinical and platelet-related variables.

Findings: VTE cases (N = 159) presented with lower platelet count and MPV vs controls (N = 140). Whole blood aggregation showed shorter collagen/Epinephrine closure times in cases, particularly within acetylsalicylic acid (ASA) users. Within ASA users, higher PRP aggregation after adenosine diphosphate (ADP), epinephrine, collagen and arachidonic acid was observed in cases vs controls. Within non-ASA and/or subjects on anticoagulants, cases presented with lower aggregation after ADP and collagen vs controls. Lower platelet-dependent TG, higher CD63 on resting and lower PAC-1 expression after collagen/ADP in-vitro stimulated platelets further characterized VTE cases vs controls, independent of therapy. Lasso regression analysis identified 26 variables associated with VTE of which 69% were platelet-related.

Interpretation: Comprehensive phenotyping of platelet function identified a large proportion of low responders to ASA in VTE cases. Lower platelet-dependent TG and lower platelet reactivity after ex-vivo stimulation characterized the "platelet exhausted syndrome" in cases. Finally, from a large array of covariates including clinical risk factors, platelet biomarkers comprised 69% of all selected variables differentiating VTE cases vs controls.

Funding: German Federal Ministry of Education and Research, CTH-Mainz and Bayer AG.
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http://dx.doi.org/10.1016/j.ebiom.2020.102978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494681PMC
October 2020

Characterization of Thrombin Generation Curve Shape in Presence of Platelets from Acute Venous Thromboembolism Patients.

J Clin Med 2020 Sep 7;9(9). Epub 2020 Sep 7.

Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.

Anticoagulant therapy, the cornerstone treatment in acute venous thromboembolism (VTE), strongly impacts thrombin generation (TG). Until now, the appearance of the TG curve in platelet rich plasma (PRP) from patients with acute VTE has not been investigated. We analyzed the shape of TG curves measured in PARP of 180 acute VTE patients. Normal shape of TG curves was observed in 110 patients, 50 patients showed no TG and 20 patients showed biphasic TG curve. The linear regression analysis, adjusted for age, sex, VTE clinical phenotypes and therapy showed that the appearance of biphasic curves is significantly associated with female sex, presence of cancer and therapy with Factor Xa inhibitors. This study demonstrated that despite taking anticoagulants, TG in presence of platelets is still present in the majority of acute VTE patients. Appearance of unusual TG curves is strongly related to the intake of anti-Factor Xa inhibitors. The clinical relevance of biphasic TG curve appearance requires further investigation.
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http://dx.doi.org/10.3390/jcm9092892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563134PMC
September 2020

GARFIELD-AF: a worldwide prospective registry of patients with atrial fibrillation at risk of stroke.

Future Cardiol 2021 01 22;17(1):19-38. Epub 2020 Jul 22.

Department of Clinical Research, Thrombosis Research Institute, London SW3 6LR, UK.

The Global Anticoagulant Registry in the Field-Atrial Fibrillation (GARFIELD-AF) examined real-world practice in a total of 57,149 (5069 retrospective, 52,080 prospective) patients with newly diagnosed AF at risk of stroke/systemic embolism, enrolled at over 1000 centers in 35 countries. It aimed to capture data on AF burden, patients' clinical profile, patterns of clinical practice and antithrombotic management, focusing on stroke/systemic embolism prevention, uptake of new oral anticoagulants, impact on death and bleeding. GARFIELD-AF set new standards for quality of data collection and analysis. A total of 36 peer-reviewed articles were already published and 73 abstracts presented at international congresses, covering treatment strategies, geographical variations in baseline risk and therapies, adverse outcomes and common comorbidities such as heart failure. A risk prediction tool as well as innovative observational studies and artificial intelligence methodologies are currently being developed by GARFIELD-AF researchers. NCT01090362 (ClinicalTrials.gov).
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http://dx.doi.org/10.2217/fca-2020-0014DOI Listing
January 2021

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

Isolated Pulmonary Embolism Is Associated With a High Risk of Arterial Thrombotic Disease: Results From the VTEval Study.

Chest 2020 07 23;158(1):341-349. Epub 2020 Mar 23.

Department of Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany. Electronic address:

Background: Isolated PE is associated with a higher burden of atherosclerotic disease than other manifestations of VTE.

Research Question: We hypothesized that the presence of isolated PE may signal a chronically elevated risk of arterial thrombotic disease.

Study Design And Methods: Data from the VTEval Study, a prospective cohort study enrolling individuals with clinical suspicion and imaging-based diagnosis or exclusion of VTE, were analyzed. Patients with PE received whole-leg ultrasonography to assess presence of DVT. Regularized logistic regression identified features that discriminate between isolated PE and other VTE phenotypes at clinical presentation. Survival analyses were performed to evaluate the crude and adjusted 3-year risks of arterial thrombotic disease, recurrent VTE, and death.

Results: The sample comprised 510 patients. Isolated PE patients (n = 63) had a distinct clinical profile from patients with other VTE phenotypes (n = 447). COPD, peripheral artery disease, atrial fibrillation, and coronary artery disease were significantly more prevalent among patients with isolated PE. Isolated PE patients had significantly higher risk (incidence rate ratio vs DVT-associated PE, 3.7 (95% CI, 1.3-10.8, P = .009); vs isolated DVT, 4.8 (1.7-14.3, P = .001) of arterial thrombotic events (ie, myocardial infarction, stroke/transient ischemic attack). After adjustment for clinical profile and medication intake, the risk of arterial thrombotic events for patients with isolated PE remained quadruple that of other VTE phenotypes (hazard ratio [HR], 3.8 [1.3-10.9], P = .01).

Interpretation: Patients with isolated PE are at higher risk for arterial thrombosis and may require screening for arterial disease and development of novel therapeutic strategies.

Clinical Trial Registration: NCT02156401.
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http://dx.doi.org/10.1016/j.chest.2020.01.055DOI Listing
July 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

Specialized Management of Oral Anticoagulation Therapy Improves Outcome in Patients with Chronic Renal Insufficiency.

J Clin Med 2020 Feb 28;9(3). Epub 2020 Feb 28.

Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.

Oral anticoagulation (OAC) is effective at preventing and treating thromboses and thromboembolism in patients with normal renal function. We aimed to research the impact of severe renal failure (RF) on patient outcome and to determine the potential benefit of caring for these patients in a specialized coagulation service (CS). A total of 1516 usual medical care patients and 756 CS-managed patients of the thrombEVAL multicenter (21 centers), prospective, cohort study (NCT01809015) were analyzed in a 3-year follow-up. Patients with RF (serum creatinine >3 mg/dL, no renal replacement therapy) were compared to patients without RF in usual care and a CS. The fluctuations in the international normalized ratios were significantly lower in CS-managed patients, and regardless of treatment in usual care or a CS, the time in therapeutic range was significantly lower in RF patients. Cox regression-adjusted hazard ratios for long-term outcome (1.5, 95% CI: 1.22-1.83, < 0.001), death (1.62, CI: 1.27-2.08, < 0.001), and hospitalization (1.21, CI: 1.02-1.44, = 0.032) were significantly higher in RF patients in usual care. Furthermore, there was a trend of more bleeding events in RF patients. CS-treated patients had significantly lower adjusted hazard ratios for death (0.24, CI: 0.14-0.39, < 0.001), hospitalizations (0.41, CI: 0.34-0.5, < 0.001), clinically relevant bleeding (0.29, CI: 0.18-0.47, < 0.001), and major bleeding (0.33, CI: 0.18-0.59, < 0.001). Thus, patients who required oral anticoagulation therapy benefitted significantly from being managed in a specialized coagulation service, regardless of their renal function.
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http://dx.doi.org/10.3390/jcm9030645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141283PMC
February 2020

Mortality risk in atrial fibrillation: the role of aspirin, vitamin K and non-vitamin K antagonists.

Int J Clin Pharm 2019 Dec 8;41(6):1536-1544. Epub 2019 Oct 8.

Department of Clinical Pharmacy and Toxicology, Maastricht University, Maastricht, The Netherlands.

Background As an alternative to vitamin K antagonist and low-dose aspirin (< 325 mg), non-vitamin K oral anticoagulants are available for the prevention of stroke in patients with atrial fibrillation. However, the mortality risk associated with these drugs in daily practice remains unclear. Objective To evaluate the risk of all-cause mortality associated with non-Vitamin K antagonist oral anticoagulants, vitamin K antagonists or aspirin in patients with atrial fibrillation. Setting A cohort study conducted among atrial fibrillation patients using the UK Clinical Practice Research Datalink (March 2008-October 2014). Method New users of vitamin K antagonists, non vitamin K oral anticoagulants, low-dose aspirin, or combination therapy were followed from the date of first prescription to the date of death, as recorded in the UK datalink. Cox proportional hazard models estimated the hazard ratio (HR) of all-cause mortality for users of NOACs, aspirin, or combination use, as compared to vitamin K antagonist. Analyses were adjusted for confounders. Main outcome measure All-cause mortality. Results We identified 31,497 patients. Non vitamin K antocoagulant use (adjusted HR [aHR] = 1.42; 95% Confidence Interval [CI] 1.18-1.71) and aspirin use (aHR = 1.64; 95% CI 1.57-1.77) were both significantly associated with a higher mortality risk than use of vitamin K antagonists. The higher mortality risk for the non vitamin K anticoagulant use was observed in men (aHR = 1.72; 95% CI 1.25-2.36), but not in women (aHR = 1.28; 95% CI 0.92-1.79. Compared to  vitamin K antagonists, mortality risk associated with the non vitamin K anticoagulants and aspirin use was significantly increased in patients with higher stroke risk (CHADS-VASc > 2). Conclusion Non vitamin K oral anticoagulants are  associated with a higher risk on all-cause mortality, particularly in men and in patients with higher stroke risk.
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http://dx.doi.org/10.1007/s11096-019-00916-1DOI Listing
December 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

Relevance of Polypharmacy for Clinical Outcome in Patients Receiving Vitamin K Antagonists.

J Am Geriatr Soc 2019 03 11;67(3):463-470. Epub 2018 Dec 11.

Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Background: Although polypharmacy is associated with a negative clinical outcome in various settings and commonly observed in patients receiving oral anticoagulation therapy, evidence on the relevance for the clinical outcome of anticoagulated patients is currently limited. The aim of the study was to investigate the effect of polypharmacy on the clinical outcomes among patients taking phenprocoumon.

Design: Prospective cohort study.

Setting: Regular medical care.

Participants: Information on 2011 individuals receiving vitamin K antagonists was available for analysis from the prospective multicenter thrombEVAL study.

Measurements: Data were obtained from clinical visits, computer-assisted interviews, and laboratory measurements. Information on clinical outcome was obtained during a 3-year follow-up period and subsequently validated via medical records.

Results: The prevalence of polypharmacy (five drugs or more) was 84.1% (n = 1691). Quality of anticoagulation therapy assessed by time in therapeutic range was lower in individuals on five to eight drugs and nine drugs or more (70.7% and 64.7%, respectively) compared with subjects without polypharmacy (73.4%). In addition, a significantly higher variability of international normalized ratio measurements was found in the presence of polypharmacy. The cumulative incidence of bleeding, hospitalization, and all-cause mortality, but not for thromboembolic events, increased across groups of medication. In adjusted Cox regression analysis, polypharmacy is an independent risk factor for bleeding (hazard ratio [HR] = 1.62; 95% confidence interval [CI] = 1.04-2.52; p = .033); hospitalization (HR = 1.60; 95% CI = 1.26-2.03; p < .001; and all-cause mortality (HR = 2.16; 95% CI = 1.43-3.27; p < .001) in a dose-dependent relationship. Per additional drug, bleeding risk was increased by 4%.

Conclusions: Polypharmacy influences the quality of anticoagulation therapy and translates into an elevated risk of adverse events in anticoagulated patients. This suggests that additional medication intake in such patients should be critically reviewed by physicians, and it highlights the importance of initiating investigations aimed at reducing multiple medication intake. J Am Geriatr Soc 67:463-470, 2019.
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http://dx.doi.org/10.1111/jgs.15712DOI Listing
March 2019

Secondary prophylaxis decision-making in venous thromboembolism: interviews on clinical practice in thirteen countries.

Res Pract Thromb Haemost 2017 Jul 20;1(1):41-48. Epub 2017 Jun 20.

Department of Epidemiology Maastricht University Masstricht The Netherlands.

Objectives: Secondary prevention of venous thromboembolism (VTE) remains a topical and contentious point of debate for thrombosis experts around the globe. This discussion centers around two aspects: optimum treatment duration and which type and dosage of thromboprophylaxis to prescribe. Collectives of thrombosis experts have tried to steer the debate by issuing periodical best-practice guidelines. However, the lack of adherence to said guidelines is such that there is a growing body of research devoted to this very problem. Most of the studies on the subject retrospectively observe a single setting, which leaves important questions as to the generalizability of their findings. As each setting appears to face its own unique challenges, the overarching question of why there is so much variance between physicians when it comes to the secondary prevention of VTE is never fully addressed.

Methods: For this study, we asked thirteen senior-level physicians representing equally as many countries about the current state of clinical practice regarding the secondary prevention of VTE.

Results: The discussion identifies several barriers to adequate VTE prevention, and hints at area-specific idiosyncrasies that may explain why physicians from different locales treat VTE patients differently.

Conclusion: Universal treatment guidelines may not fully translate to clinical practice in many areas, and that promoting local guidelines to supplement the universal guidelines may be beneficial.
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http://dx.doi.org/10.1002/rth2.12014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058202PMC
July 2017

Determinants of treatment duration in the prevention of recurrent venous thromboembolism: a protocol for a balanced vignette experiment.

BMJ Open 2017 05 10;7(5):e015231. Epub 2017 May 10.

Department of Epidemiology, Maastricht University Medical Center, Maastricht, The Netherlands.

Introduction: Venous thromboembolism (VTE) is a condition that annually occurs in approximately 1‰ of the world's population. Patients who have already had a VTE are at elevated risk for a recurrent VTE. Recurrent events increase the risk of long-term sequelae and can be fatal. Adequate secondary prophylaxis is thus needed to prevent such events. Patients with VTE are often prone to bleeding, and pharmacological prophylaxis exacerbates bleeding risk. Expert opinions on the optimum duration of secondary prophylaxis in VTE still vary substantially. The existence of treatment guidelines has not led to uniformity of VTE secondary prophylaxis strategies, which means that physicians still adhere to individual risk calculi in determining treatment duration.

Methods And Analysis: The aim of this study is to establish what factors lie at the root of this variance in VTE secondary prophylactic treatment strategies, and what risk factors are deemed of particular importance in determining the perceived risks and benefits of variable treatment durations. To do this, we created a survey based on a D-efficient and G-efficient balanced experimental vignette design. This protocol covers all aspects of how this survey was set up and how it was implemented. The analysis of the experimental data will be carried out using mixed-effects methods, which are beneficial in scenarios with high interindividual variance and correlated (eg, repeated-measures) responses. We propose the use of maximal random effects structures insofar as possible.

Ethics And Dissemination: All data are de-identified, and any identifying characteristics of the respondents will not be reported in a final manuscript or elsewhere. A paper describing the expert interviews is currently under peer review. A manuscript that contains the analysis of the results of the experiment described in this protocol is being drafted, and will also be submitted to a peer-reviewed journal.
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http://dx.doi.org/10.1136/bmjopen-2016-015231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777455PMC
May 2017
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