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Position Paper from the Second Maastricht Consensus Conference on Thrombosis

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Position Paper from the Second Maastricht Consensus Conference on Thrombosis Consensus Document 229 Atherothrombosis and Thromboembolism: Position Paper from the Second Maastricht Consensus Conference on Thrombosis H. M. H. Spronk1 T. Padro2 J. E. Siland3 J. H. Prochaska4 J. Winters5 A. C. van der Wal6 J. J. Posthuma1 G. Lowe7 E. d’Alessandro5,6 P. Wenzel8 D. M. Coenen9 P. H. Reitsma10 W. Ruf4 R. H. van Gorp9 R. R. Koenen9 T. Vajen9 N. A. Alshaikh9 A. S. Wolberg11 F. L. Macrae12 N. Asquith12 J. Heemskerk9 A. Heinzmann9 M. Moorlag13 N. Mackman14 P. van der Meijden9 J. C. M. Meijers15 M. Heestermans10 T. Renné16,17 S. Dólleman18 W. Chayouâ13 R. A. S. Ariëns12 C. C. Baaten9 M. Nagy9 A. Kuliopulos19 J. J. Posma1 P. Harrison20 M. J. Vries1 H. J. G. M. Crijns21 E. A. M. P. Dudink21 H. R. Buller22 Y. M.C. Henskens1 A. Själander23 S. Zwaveling1,13 O. Erküner21 J. W. Eikelboom24 A. Gulpen1 F. E. C. M. Peeters21 J. Douxfils25 R. H. Olie1 T. Baglin26 A. Leader1,27 U. Schotten4 B. Scaf1,5 H. M. M. van Beusekom28 L. O. Mosnier29 L. van der Vorm13 P. Declerck30 M. Visser31 D. W. J. Dippel32 V. J. Strijbis13 K. Pertiwi33 A. J. ten Cate-Hoek1 H. ten Cate1 1 Laboratory for Clinical Thrombosis and Haemostasis, 17Institute of Clinical Chemistry and Laboratory Medicine, University Cardiovascular Research Institute Maastricht (CARIM), Maastricht Medical Center Hamburg-Eppendorf, Hamburg, Germany University Medical Center, Maastricht, The Netherlands 18Department of Nephrology, Leiden University Medical Centre, 2 Cardiovascular Research Center (ICCC), Hospital Sant Pau, Leiden, The Netherlands Barcelona, Spain 19Tufts University School of Graduate Biomedical Sciences, 3 Department of Cardiology, University Medical Center Groningen, Biochemistry/Developmental, Molecular and Chemical Biology, Groningen, The Netherlands Tufts University School of Medicine, Boston, Massachusetts 4 Center for Cardiology/Center for Thrombosis and Hemostasis/ 20Institute of Inflammation and Ageing, University of Birmingham, DZHK, University Medical Center of the Johannes Gutenberg Birmingham, United Kingdom University Mainz, Mainz, Germany 21Department of Cardiology, Cardiovascular Research Institute 5 Department of Physiology, Cardiovascular Research Institute Maastricht Maastricht (CARIM), Maastricht University Medical Center, (CARIM), Maastricht University, Maastricht, The Netherlands Maastricht, The Netherlands 6 Department of Pathology, Academic Medical Center (AMC), 22Department of Vascular Medicine, Academic Medical Center Amsterdam, The Netherlands (AMC), Amsterdam, The Netherlands 7 Institute of Cardiovascular and Medical Sciences, University of 23Department of Public Health and Clinical Medicine, Umeå Glasgow, Glasgow, Scotland University, Umeå, Sweden 8 Department of Cardiology, Universitätsmedizin Mainz, Mainz, Germany 24 9 Department of Biochemistry, Cardiovascular Research Institute Department of Medicine, McMaster University, Hamilton, Ontario, Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands Canada 25 10Einthoven Laboratory, Leiden University Medical Center, Leiden, Department of Pharmacy, Thrombosis and Hemostasis Center, The Netherlands Faculty of Medicine, Namur University, Namur, Belgium 26 11Department of Pathology and Laboratory Medicine, University of Department of Haematology, Addenbrookes Hospital Cambridge, North Carolina, Chapel Hill, North Carolina, United States Cambridge, United Kingdom 27 12Thrombosis and Tissue Repair Group, Division of Cardiovascular and Davidoff Cancer Center, Rabin Medical Center, Institute of Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Hematology, Sackler Faculty of Medicine, Tel Aviv University, Medicine, School of Medicine, University of Leeds, Leeds, UK Petah Tikva, Tel Aviv, Israel 28 13Synapse, Maastricht, The Netherlands Department of Experimental Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. 14Department of Medicine, UNC McAllister Heart Institute, University 29 of North Carolina, Chapel Hill, North Carolina, United States Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, United States 15Department of Plasma Proteins, Sanquin, Amsterdam, 30 The Netherlands Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Leuven, Belgium 16Department of Molecular Medicine and Surgery, Karolinska 31 Institutet and University Hospital, Stockholm, Sweden, Bayer AG, Wuppertal, Germany 32Department of Neurology, Erasmus MC, Rotterdam, The Netherlands 33Department of Cardiovascular Pathology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands Thromb Haemost 2018;118:229–250. received Copyright © 2018 Schattauer DOI https://doi.org/ July 20, 2017 10.1160/TH17-07-0492. accepted after revision ISSN 0340-6245. October 30, 2017 230 Atherothrombosis and Thromboembolism Spronk et al. Address for correspondence Hugo ten Cate, MD, PhD, Laboratory for Clinical Thrombosis and Haemostasis, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, P.O. Box 616, UNS50: Box 8, 6200 MD Maastricht, The Netherlands (e-mail: [email protected]). Abstract Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including athero- sclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorpo- rated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1. Risk factors, biomarkers and plaque instability: In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in)stability; proteomic and metabolomics data are to be added to genetic information. 2. Circulating cells including platelets and atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; disease mechanism-based biomarkers need to be identified; experimental systems are needed that incorporate whole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation. 3. Coagulation proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin–angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet–fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences. 4. Preventive and acute treatment of atherothrombosis and arterial embolism; novel ways and tailoring? The role of protease-activated receptor (PAR)-4 vis à vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based Keywords antiplatelet therapy adjustment support development of practically feasible tests; risk fi fi This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. ► atherothrombosis scores for patients with atrial brillation need re nement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences ► arterial thrombosis in bleeding may have added value; all forms of oral anticoagulant treatment require ► coagulation better organization, including education and emergency access; laboratory testing still ► platelets needs rapidly available sensitive tests with short turnaround time. ► antiplatelet therapy 5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia–reperfusion: ► anticoagulants Biobanks specifically for thrombus storage and analysis are needed; further studies on ► atherosclerosis novel modified activated protein C–based agents are required including its cytoprotective ► ischaemic stroke properties; new avenues for optimizing treatment of patients with ischaemic stroke are fi ► atrial fibrillation needed, also including novel agents that modify brinolytic activity (aimed at plasmino- gen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor. ► myocardial infarction Thrombosis and Haemostasis Vol. 118 No. 2/2018 Atherothrombosis and Thromboembolism Spronk et al. 231 Introduction fat accumulation rather than overall obesity is responsible for increased cardiometabolic risk and isa better predictor for CVD, – During the second Maastricht Consensus Conference on including atrial fibrillation (AF) and heart failure.8 10 Ectopic fat Thrombosis (MCCT), atherothrombosis and cardiovascular refers to fat
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