UvA-DARE (Digital Academic Repository) Hypercoagulability in hematological malignancies Lauw, M.N. Link to publication Citation for published version (APA): Lauw, M. N. (2015). Hypercoagulability in hematological malignancies 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: http://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 (http://dare.uva.nl) Download date: 05 Jan 2019
ISBN 978-94-6169-709-7 Mandy N. Lauw Patients with cancer are at high risk for venous thrombosis, the undesired formation of blood clots within the veins. Historically, this high risk was mainly attributed to patients with solid tumors, but recent studies have indicated that the risk is at least as high or even higher in patients with hematological malignancies, such as lymphoma, multiple myeloma and leukemia, especially acute lymphoblastic leukemia. Venous thrombosis can cause life-long morbidity or can be fatal, and requires anticoagulant treatment with the accompanying risk of bleeding. Moreover, thrombosis can lead to suboptimal treatment of the malignancy, due to the necessity to interrupt, delay or even discontinue treatment. This thesis consists of three parts; in Part I, the relationship between venous thrombosis and cancer is highlighted and illustrated with a fascinating case. Part II focuses on two distinct risk factors for hypercoagulability, the JAK2V617F mutation and nucleosomes. In Part III, the incidence, pathogenesis and prevention of venous thrombosis in acute lymphoblastic leukemia are investigated. This thesis aims to increase insight in the risk factors and mechanisms behind the hypercoagulable state in hematological malignancies. This will help to improve prevention of venous thrombosis in patients with a hematological malignancy, particularly with acute lymphoblastic leukemia. Mandy N. Lauw Hypercoagulability in Hematological Malignancies Hypercoagulability in H ematological Malignancies Hypercoagulability in Hematological Malignancies Mandy N. Lauw
Hypercoagulability in Hematological Malignancies Mandy N. Lauw
Colofon Hypercoagulability in Hematological Malignancies PhD Thesis, University of Amsterdam, The Netherlands ISBN: 978-94-6169-709-7 Author: Mandy Nicole Lauw Lay-out, cover design and printing: Optima Grafische Communicatie, Rotterdam, The Netherlands Financial support by the AMC Graduate School, ZonMw and the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged. Printing of this thesis was financially supported by: Academisch Medisch Centrum /, Amgen bv, Aspen Netherlands bv, Bayer Healthcare bv, Boehringer Ingelheim bv, Bristol-Myers Squibb Oncology bv, Celgene bv, ChipSoft bv, CSL Behring bv, Daiichi Sankyo Nederland bv, Federatie van Nederlandse Trombosediensten, Janssen-Cilag bv, LEO Pharma bv, medi Nederland bv, Pfizer bv, Sanofi-Aventis Nederland bv, Sanquin Plasma Products bv, Servier Nederland Farma, Stichting AMSTOL, Stichting tot Steun Promovendi Vasculaire Geneeskunde, Takeda Nederland bv. Copyright 2015 Mandy N. Lauw, Amsterdam, The Netherlands All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means, without the explicit written permission of the author or the copyright owning journal.
Hypercoagulability in Hematological Malignancies ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad van doctor aan de op gezag van de Rector Magnificus prof. dr. D.C. van den Boom ten overstaan van een door het College van Promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel op vrijdag 4 september 2015, te 12:00 uur door Mandy Nicole Lauw geboren te Hilversum
Promotiecommissie Promotores: Prof. dr. S. Middeldorp Prof. dr. M.H.J. van Oers Copromotor: Dr. B.J. Biemond Overige leden: Prof dr. H.R. Büller Prof. dr. M.M. Levi Prof. dr. Y.B.W.E.M. Roos Prof. dr. F.W.G. Leebeek Prof. dr. S. Zweegman Dr. C.H. van Ommen Erasmus Universiteit Rotterdam Vrije Universiteit Amsterdam Faculteit der Geneeskunde
Our greatest glory is not in never falling, but in rising every time we fall. Confucius
Table of Contents Chapter 1 General introduction and Outline of the thesis 9 PART I Chapter 2 Chapter 3 Venous Thromboembolism and Cancer Cancer and venous thrombosis; Current comprehensions and future directions Semin. Thromb. Hemost. 2013 Jul;39(5):507-14. Leukemic transformation of essential thrombocythemia masked by recurrence of venous thromboembolism; A case report Submitted 27 45 PART II Chapter 4 Chapter 5 Chapter 6 Chapter 7 Hypercoagulability; JAK2V617F mutation and Nucleosomes Relevance of the JAK2V617F mutation in patients with deep vein thrombosis of the leg without overt myeloproliferative neoplasm Ann Hematol. 2012 Jan;91(1):103-7. Prevalence of JAK2V617F mutation in women with unexplained recurrent miscarriage J Thromb Haemost. 2010 Dec;8:2837 9. Circulating nucleosomes and neutrophil activation as risk factors for deep vein thrombosis Arterioscler Thromb Vasc Biol. 2013 Jan;33(1):147-51. Circulating nucleosomes, neutrophil activation and development of venous thrombosis in patients with multiple myeloma Submitted 57 69 77 89 6
PART III Chapter 8 Chapter 9 Chapter 10 Chapter 11 Chapter 12 Chapter 13 Venous Thromboembolism in Acute Lymphoblastic Leukemia Age is the main clinical risk factor for venous thromboembolism within a large cohort of children with acute lymphoblastic leukemia Submitted Clinical course of cerebral venous thrombosis in adults with acute lymphoblastic leukemia J Stroke Cerebrovasc Dis. 2015 Jul;24(7):1679-84. Cerebral venous thrombosis and thrombophilia; A systematic review and meta-analysis Semin Thromb Hemost. 2013 Nov;39(8):913-27. Venous thromboembolism in adults treated for acute lymphoblastic leukemia; Effect of fresh frozen plasma supplementation Thromb Haemost. 2013 Apr;109(4):633-42. Prophylaxis for venous thromboembolism during asparaginase therapy in patients treated for acute lymphoblastic leukemia Cochrane Database Syst Rev. 2015 Prevention of venous thromboembolism with low-molecularweight heparin in adults treated for acute lymphoblastic leukemia; HOVON-100 thromboprophylaxis study protocol Submitted 109 125 141 169 189 221 Chapter 14 Summary and Future perspectives 237 Chapter 15 Nederlandse samenvatting 251 Appendices Authors and Affiliations 265 List of Publications 279 Portfolio 279 Curriculum Vitae 283 Dankwoord 287 7