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1. Antithrombotic Therapy: Prevention and Treatment of Atherosclerosis and Atherothrombosis

Author

Olie, R. H., van der Meijden, P. E. J., Spronk, H. M. H., ten Cate, H., Barrett, James E., Editor-in-Chief, Flockerzi, Veit, Editorial Board Member, Frohman, Michael A., Editorial Board Member, Geppetti, Pierangelo, Editorial Board Member, Hofmann, Franz B., Editorial Board Member, Kuner, Rohini, Editorial Board Member, Michel, Martin C., Editorial Board Member, Page, Clive P., Editorial Board Member, Wang, KeWei, Editorial Board Member, von Eckardstein, Arnold, editor, and Binder, Christoph J., editor

Published
2022
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4. Lupus anticoagulant associates with thrombosis in patients with COVID-19 admitted to intensive care units

Author

Noordermeer, Tessa, Schutgens, Roger E. G., Visser, Chantal, Rademaker, Emma, de Maat, Moniek P. M., Jansen, A. J. Gerard, Limper, Maarten, Cremer, Olaf L., Kruip, Marieke J. H. A., Endeman, Henrik, Maas, Coen, de Laat, Bas, Urbanus, Rolf T., van de Beek, D., Brouwer, M. C., de Bruin, S., Coppens, M., van Es, N., van Haaps, T. F., Juffermans, N. P., Muller, M. C. A., Vlaar, A. P. J., Hertogh, C. M. P. M., Heunks, L. M. A., Hugtenburg, J. G., van Kooten, J., Nossent, E. J., Smulders, Y., Tuinman, P. R., Noordegraaf, A. Vonk, Grootenboers, M. J. J. H., van Guldener, C., Kant, M., Lansbergen, A., Faber, J., Hajer, G., Stemerdink, A., van den Akker, J., Bierings, R., Endeman, H., Goeijenbier, M., Hunfeld, N. G. M., van Gorp, E. C. M., Gommers, D. A. M. P. J., Koopmans, M. P. G., Kruip, M. J. H. A., Kuiken, T., Langerak, T., Leebeek, Lauw, M. N., de Maat, M. P. M., Noack, D., Paats, M. S., Raadsen, M. P., Rockx, B., Rokx, C., Schurink, C. A. M., Tong-Minh, K., van den Toorn, L., den Uil, C. A., Visser, C., Boutkourt, F., Roest, T., Douma, R. A., de Haan, L. R., ten Wolde, M., Bemelmans, R. H. H., Festen, B., Stads, S., de Jager, C. P. C., Simons, K. S., Antoni, M. L., Bos, M. H., Burggraaf, J. L. I., Cannegieter, S. C., Eikenboom, H. C. J., den Exter, P. L., Geelhoed, J. J. M., Huisman, M. V., de Jonge, E., Kaptein, F. H. J., Klok, F. A., Kroft, L. J. M., Lijfering, W. M., Nab, L., Ninaber, M. K., Putter, H., Ramai, S. R. S., da Rocha Rondon, A. M., Roukens, A. H. E., Stals, M. A. M., Versteeg, H. H., Vliegen, H. W., van Vlijmen, B. J. M., van de Berg, T., Bruggemann, R., van Bussel, B. C. T., ten Cate, H., ten Cate-Hoek, A., Hackeng, T. M., Henskens, ir. Y., Hulshof, A., Mulder, M., Olie, R. H., Schurgers, L., Spaetgens, B., Spronk, H., Spruit, M. A., Winckers, K., Nieuwenhuizen, L., Franken, B., Schrover, I. M., de Waal, E. G. M., Beishuizen, A., Cornet, A., Krabbe, J., Kramers, K., Leentjens, J., de Mast, Q., Middeldorp, S., Brouwer, R. E., Ellerbroek, J. L. J., Tijmensen, J., Hovens, M. M. C., Oostdijk, E. A. N., Westerhof, B. D., Faber, L. M., van den Biggelaar, M., Meijers, J. C. M., Voorberg, J., Kevenaar, M. E., Soei, Y. L., Wils, E. J., Croles, F. N., de Laat, B., Kamphuisen, P. W., Vink, R., Lisman, T., Meijer, K., van Tichelaar, Y. I. G., Cremer, O. L., Geersing, G., Kaasjager, H. A. H., Kusadasi, N., Huisman, A., Maas, C., Nijkeuter, M., Schutgens, R. E. G., Creveldkliniek, Van, Urbanus, R. T., Westerink, J., Faber, H. J., Koster, S. C. E., van Montfort, P., van Twist, D. J. L., RS: Carim - B01 Blood proteins & engineering, Biochemie, Hematology, Intensive Care, Neurology, ANS - Neuroinfection & -inflammation, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, AII - Inflammatory diseases, Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, Graduate School, ACS - Microcirculation, Medical Microbiology and Infection Prevention, ARD - Amsterdam Reproduction and Development, Experimental Vascular Medicine, Landsteiner Laboratory, ACS - Atherosclerosis & ischemic syndromes, Elderly care medicine, APH - Aging & Later Life, Clinical pharmacology and pharmacy, APH - Health Behaviors & Chronic Diseases, Pulmonary medicine, Internal medicine, ACS - Diabetes & metabolism, Intensive care medicine, General practice, and Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], lupus anticoagulant, risk factor, critically ill, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], COVID-19, Hematology, thrombosis, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18]
Abstract

Contains fulltext : 286889.pdf (Publisher’s version ) (Open Access) BACKGROUND: Thrombosis is a frequent and severe complication in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) is a strong acquired risk factor for thrombosis in various diseases and is frequently observed in patients with COVID-19. Whether LA is associated with thrombosis in patients with severe COVID-19 is currently unclear. OBJECTIVE: To investigate if LA is associated with thrombosis in critically ill patients with COVID-19. PATIENTS/METHODS: The presence of LA and other antiphospholipid antibodies was assessed in patients with COVID-19 admitted to the ICU. LA was determined with dilute Russell's viper venom time (dRVVT) and LA-sensitive activated partial thromboplastin time (aPTT) reagents. RESULTS: Of 169 patients with COVID-19, 116 (69%) tested positive for at least one antiphospholipid antibody upon admission to the ICU. Forty (24%) patients tested positive for LA; of whom 29 (17%) tested positive with a dRVVT, 19 (11%) tested positive with an LA-sensitive aPTT, and 8 (5%) tested positive on both tests. Fifty-eight (34%) patients developed thrombosis after ICU admission. The odds ratio (OR) for thrombosis in patients with LA based on a dRVVT was 2.5 (95% confidence interval [CI], 1.1-5.7), which increased to 4.5 (95% CI, 1.4-14.3) in patients at or below the median age in this study (64 years). LA positivity based on a dRVVT or LA-sensitive aPTT was only associated with thrombosis in patients aged less than 65 years (OR, 3.8; 95% CI, 1.3-11.4) and disappeared after adjustment for C-reactive protein. CONCLUSION: Lupus anticoagulant on admission is strongly associated with thrombosis in critically ill patients with COVID-19, especially in patients aged less than 65 years.

Published
2022

7. Atherothrombosis and Thromboembolism : Position Paper from the Second Maastricht Consensus Conference on Thrombosis

Author

Spronk, H. M. H., Padro, T., Siland, J. E., Prochaska, J. H., Winters, J., van der Wal, A. C., Posthuma, J. J., Lowe, G., d'Alessandro, E., Wenzel, P., Coenen, D. M., Reitsma, P. H., Ruf, W., van Gorp, R. H., Koenen, R. R., Vajen, T., Alshaikh, N. A., Wolberg, A. S., Macrae, F. L., Asquith, N., Heemskerk, J., Heinzmann, A., Moorlag, M., Mackman, N., van der Meijden, P., Meijers, J. C. M., Heestermans, M., Renne, T., Dolleman, S., Chayoua, W., Ariens, R. A. S., Baaten, C. C., Nagy, M., Kuliopulos, A., Posma, J. J., Harrison, P., Vries, M. J., Crijns, H. J. G. M., Dudink, E. A. M. P., Buller, H. R., Henskens, Y. M. C., Själander, Anders, Zwaveling, S., Erkuner, O., Eikelboom, J. W., Gulpen, A., Peeters, F. E. C. M., Douxfils, J., Olie, R. H., Baglin, T., Leader, A., Schotten, U., Scaf, B., van Beusekom, H. M. M., Mosnier, L. O., van der Vorm, L., Declerck, P., Visser, M., Dippel, D. W. J., Strijbis, V. J., Pertiwi, K., ten Cate-Hoek, A. J., ten Cate, H., Spronk, H. M. H., Padro, T., Siland, J. E., Prochaska, J. H., Winters, J., van der Wal, A. C., Posthuma, J. J., Lowe, G., d'Alessandro, E., Wenzel, P., Coenen, D. M., Reitsma, P. H., Ruf, W., van Gorp, R. H., Koenen, R. R., Vajen, T., Alshaikh, N. A., Wolberg, A. S., Macrae, F. L., Asquith, N., Heemskerk, J., Heinzmann, A., Moorlag, M., Mackman, N., van der Meijden, P., Meijers, J. C. M., Heestermans, M., Renne, T., Dolleman, S., Chayoua, W., Ariens, R. A. S., Baaten, C. C., Nagy, M., Kuliopulos, A., Posma, J. J., Harrison, P., Vries, M. J., Crijns, H. J. G. M., Dudink, E. A. M. P., Buller, H. R., Henskens, Y. M. C., Själander, Anders, Zwaveling, S., Erkuner, O., Eikelboom, J. W., Gulpen, A., Peeters, F. E. C. M., Douxfils, J., Olie, R. H., Baglin, T., Leader, A., Schotten, U., Scaf, B., van Beusekom, H. M. M., Mosnier, L. O., van der Vorm, L., Declerck, P., Visser, M., Dippel, D. W. J., Strijbis, V. J., Pertiwi, K., ten Cate-Hoek, A. J., and ten Cate, H.

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 atherosclerosis. 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 incorporated 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; diseasemechanism-based biomarkers need to be identified; experimental systems are needed that incorporatewhole-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 b

Published
2018
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8. Direct oral anticoagulants: When to consider laboratory testing?

Author

ten Cate, H., Olie, R. H., ten Cate-Hoek, A. J., Henskens, Y. M. C., ten Cate, H., Olie, R. H., ten Cate-Hoek, A. J., and Henskens, Y. M. C.

Abstract

Introduction: Direct oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic stroke, as well as for prevention and treatment of venous thromboembolism. Dose adjustment based on laboratory testing is not required; however, there are several potential situations that deserve insight into a DOAC plasma activity level. Methods: Based on a series of real-life case descriptions, we discuss indications for dedicated DOAC testing, as well as the interpretation and consequences. Results: Testing of DOACs in selected patients may help to better interpret acute situations such as bleeding or thrombosis while on anticoagulation, but also suspected drug failure, drug accumulation, or lack of adherence. Conclusion: The 24/7 availability of target-specific tests with adequate calibration is recommended to support the clinician in the interpretation and where needed adjustment of the management of patients on DOACs. The relevance of laboratory-guided DOAC management, particularly in the elderly, merits further study.

Published
2018

12. Atherothrombosis and Thromboembolism: Position Paper from the Second Maastricht Consensus Conference on Thrombosis.

Author

Spronk HMH, Padro T, Siland JE, Prochaska JH, Winters J, van der Wal AC, Posthuma JJ, Lowe G, d'Alessandro E, Wenzel P, Coenen DM, Reitsma PH, Ruf W, van Gorp RH, Koenen RR, Vajen T, Alshaikh NA, Wolberg AS, Macrae FL, Asquith N, Heemskerk J, Heinzmann A, Moorlag M, Mackman N, van der Meijden P, Meijers JCM, Heestermans M, Renné T, Dólleman S, Chayouâ W, Ariëns RAS, Baaten CC, Nagy M, Kuliopulos A, Posma JJ, Harrison P, Vries MJ, Crijns HJGM, Dudink EAMP, Buller HR, Henskens YMC, Själander A, Zwaveling S, Erküner O, Eikelboom JW, Gulpen A, Peeters FECM, Douxfils J, Olie RH, Baglin T, Leader A, Schotten U, Scaf B, van Beusekom HMM, Mosnier LO, van der Vorm L, Declerck P, Visser M, Dippel DWJ, Strijbis VJ, Pertiwi K, Ten Cate-Hoek AJ, and Ten Cate H

Subjects
Anticoagulants therapeutic use, Biomarkers blood, Blood Coagulation, Erythrocytes metabolism, Factor VIII metabolism, Factor XII metabolism, Factor XIII metabolism, Humans, Macrophages metabolism, Netherlands, Phenotype, Plaque, Atherosclerotic blood, Plaque, Atherosclerotic diagnosis, Plaque, Atherosclerotic therapy, Polyphosphates metabolism, Risk Factors, Signal Transduction, Thromboembolism blood, Thromboembolism diagnosis, Thrombosis diagnosis, Thromboembolism therapy, Thrombosis blood, Thrombosis therapy
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 atherosclerosis. 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 incorporated 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 antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time. 5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia-reperfusion: Biobanks specifically for thrombus storage and analysis are needed; further studies on novel modified activated protein C-based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor., Competing Interests: None declared., (Schattauer GmbH Stuttgart.)

Published
2018
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