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Thesis Explores Endocrine Determinants of the Haemostatic Hormone

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Thesis Explores Endocrine Determinants of the Haemostatic Hormone UvA-DARE (Digital Academic Repository) Endocrine determinants of haemostasis and thrombosis risk: Focus on thyroid hormone Elbers, L.P.B. Publication date 2016 Document Version Final published version Link to publication Citation for published version (APA): Elbers, L. P. B. (2016). Endocrine determinants of haemostasis and thrombosis risk: Focus on thyroid hormone. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:10 Oct 2021 Endocrine Determinants of Haemostasis and Thrombosis Risk – Risk Thrombosis and of Haemostasis Determinants Endocrine UITNODIGING Voor het bijwonen van de openbare verdediging van het proefschrift This thesis explores endocrine determinants of the haemostatic Endocrine Determinants of system and thrombosis risk with main focus on thyroid hormone. Haemostasis and It describes, in three parts, the effects of thyroid hormone on the Thrombosis Risk haemostatic system, the effects of thyroid hormone (mimetics) Focus on Thyroid Hormone on lipids and the effects of other hormones on the haemostatic system and thrombosis risk. door Laura Elbers Dinsdag 1 november om 12.00 uur Agnietenkapel Oudezijds Voorburgwal 231 te Amsterdam Laura Elbers Focus on Thyroid Hormone on Thyroid Focus Amstelvlietstraat 529 1096 GG Amsterdam 06-54618927 [email protected] Endocrine Determinants of Haemostasis and Thrombosis Risk Focus on Thyroid Hormone Paranimfen Marjolein Brekelmans [email protected] Laura Elbers Paula Wolvers [email protected] Laura Elbers Laura Endocrine determinants Endocrine of determinants haemostasis and thrombosis risk – Endocrine of determinants haemostasis and thrombosis risk – UITNODIGINGUITNODIGING VoorVoor het het bijwonen bijwonen van van de de openbare openbare verdedigingverdediging van van het het proefschrift proefschrift EndocrineEndocrine Determinants Determinants of of ThisThis thesis thesis explores explores endocrine endocrine determinants determinants of of the the haemostatic haemostatic HaemostasisHaemostasis and and systemsystem and and thrombosis thrombosis risk risk with with main main focus focus on on thyroid thyroid hormone. hormone. ThrombosisThrombosis Risk Risk It Itdescribes, describes, in in three three parts, parts, the the effects effects of ofthyroid thyroid hormone hormone on on the the FocusFocus on on Thyroid Thyroid Hormone Hormone haemostatichaemostatic system, system, the the effects effects of ofthyroid thyroid hormone hormone (mimetics)(mimetics) on on lipidslipids and and the the effects effects of ofother other hormones hormones on on the the haemostatic haemostatic system system andand thrombosis thrombosis risk. risk. doordoor Laura Laura Elbers Elbers DinsdagDinsdag 1 november 1 november omom 12.00 12.00 uur uur AgnietenkapelAgnietenkapel OudezijdsOudezijds Voorburgwal Voorburgwal 231 231 te teAmsterdam Amsterdam LauraLaura Elbers Elbers AmstelvlietstraatAmstelvlietstraat 529 529 Focus Focus on hormone thyroid Focus on hormone thyroid 10961096 GG GG Amsterdam Amsterdam 06-5461892706-54618927 [email protected]@amc.uva.nl EndocrineEndocrine Determinants Determinants of of Haemostasis Haemostasis and and Thrombosis Thrombosis Risk Risk ParanimfenParanimfen FocusFocus on on Thyroid Thyroid Hormone Hormone MarjoleinMarjolein Brekelmans Brekelmans [email protected]@amc.uva.nl PaulaPaula Wolvers Wolvers LauraLaura Elbers Elbers [email protected]@slz.nl Laura Laura Elbers Laura Elbers Endocrine Determinants of Haemostasis and Thrombosis Risk - Focus on Thyroid Hormone Academic thesis, University of Amsterdam, Amsterdam, The Netherlands ISBN: 978-94-6233-407-6 Author: Laura Elbers Cover design: From the project Heart Bloom by Rogier Arents and Bin Yu Lay-out and printing: Gildeprint – Enschede © Laura Elbers Printing of this thesis was financially supported by Stichting Klinisch Wetenschap- pelijk Onderzoek Slotervaartziekenhuis, Stichting tot Steun Promovendi Vasculaire Geneeskunde, Universiteit van Amsterdam, Novo Nordisk, LEO Pharma, Bayer BV and ChipSoft. Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged. Endocrine Determinants of Haemostasis and Thrombosis Risk - Focus on Thyroid Hormone ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus prof. dr. ir. K.I.J. Maex ten overstaan van een door het College voor Promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel op dinsdag 1 november 2016, te 12:00 uur door Laurentia Petronella Bernardina Elbers geboren te Gouda PROMOTIECOMMISSIE: Promotores: Prof. dr. D.P.M. Brandjes Universiteit van Amsterdam Prof. dr. E. Fliers Universiteit van Amsterdam Copromotores: Dr. V.E.A. Gerdes Universiteit van Amsterdam Prof. dr. S.C. Cannegieter Universiteit Leiden Overige leden: Dr. A. Boelen Universiteit van Amsterdam Prof. dr. S. Middeldorp Universiteit van Amsterdam Prof. dr. M. Goddijn Universiteit van Amsterdam Prof. dr. F.R. Rosendaal Universiteit Leiden Prof. dr. R.P. Peeters Erasmus Universiteit Rotterdam Prof. dr. M. den Heijer Vrije Universiteit Amsterdam Faculteit der Geneeskunde Voor mijn ouders CONTENTS Chapter 1 General introduction and outline of the thesis 11 Part I Thyroid hormone and the haemostatic system 21 Chapter 2 The influence of thyroid function on the coagulation 23 system and its clinical consequences Chapter 3 The effect of levothyroxine on expression of inflammation- 47 related genes in healthy subjects: a controlled randomized crossover study Chapter 4 The hypercoagulable state in hyperthyroidism is mediated 61 via the thyroid hormone β receptor pathway Chapter 5 Plasma levels of free thyroxine and the risk of major 79 bleeding in bariatric surgery Part II Thyroid hormone (mimetics) and lipids 95 Chapter 6 Thyroid hormone mimetics: the past, current status and 97 future challenges Chapter 7 Effects of supra-physiological levothyroxine dosages 111 on liver parameters, lipids and lipoproteins in healthy volunteers: a randomized controlled crossover study Part III Other hormones and the haemostatic system 129 Chapter 8 Variation in the glucocorticoid receptor gene and risk of 131 venous thromboembolism Chapter 9 Prolactin levels and haemostatic changes during pregnancy 149 and after delivery Chapter 10 Left-sided predominance of deep venous thrombosis in the 167 postpartum period Chapter 11 Coagulation and fibrinolysis in hyperparathyroidism 179 secondary to vitamin D deficiency Chapter 12 Effects of mineralocorticoid receptor antagonists on the 197 risk of thrombosis, bleeding and mortality: a meta-analysis of randomized controlled trials Author’s affiliations 229 PhD portfolio 235 List of publications 241 Summary and general discussion 245 Samenvatting en algemene discussie 255 Curriculum vitae 269 Dankwoord 273 1 General Introduction and Outline of the Thesis GENERAL INTRODUCTION In June 1905, Ernest Starling (1866-1927) first used the word ‘hormone’ which was derived from the Greek word ‘ormao’ meaning ‘to arouse or excite’ (1). Hor- mones were defined as ‘the chemical messengers which, speeding from cell to cell along the blood stream, may coordinate the activities and growth of different parts of the body’. During the subsequent 100 years, the knowledge on hormones has expanded widely and this led to various therapeutic options for various dis- eases (2). Hormones exert their action by binding to tissue-specific receptors. The hormone-receptor complex then increases or decreases gene transcription. By this mechanism, hormones may alter protein synthesis in various tissues. In this thesis we aimed to explore the hormonal influence on the haemostatic system and its potential clinical consequences. Haemostasis is the process that maintains the integrity of a closed circulatory system after vascular damage (3). Primary haemostasis is defined as the forma- tion of the primary platelet plug. Secondary haemostasis is the process of fibrin formation to stabilize the platelet plug. The process of dissolution of fibrin in blood clots is called fibrinolysis. These physiological processes may be unbalanced which results in pathology, e.g., arterial or venous thrombosis. The most common pre- sentations of venous thrombosis are deep vein thrombosis of the lower extremity and pulmonary embolism which can be life-threatening. Myocardial infarction and ischemic stroke are the most common presentations of arterial thrombosis. Hormones may influence the risk of both arterial and venous thrombosis via different mechanisms. The effect on arterial thrombosis is mainly indirect. For instance, thyroid hormone stimulates the clearance
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