Pathophysiology and management of hemostatic alterations in cirrhosis and liver transplantation Arshad, Freeha

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University of Groningen Pathophysiology and management of hemostatic alterations in cirrhosis and liver transplantation Arshad, Freeha IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2016 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Arshad, F. (2016). Pathophysiology and management of hemostatic alterations in cirrhosis and liver transplantation [Groningen]: Rijksuniversiteit Groningen Copyright Other than for strictly personal use, 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), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 11-01-2018

Pathophysiology and Management of Hemostatic Alterations in Cirrhosis and Liver Transplantation Freeha Arshad

The study described in Chapter 7 was partially funded by Sanquin Plasma Products B.V. For printing of this thesis, financial support of the following institutions and companies is gratefully acknowledged: Arshad, F Pathophysiology and management of hemostatic alterations in cirrhosis and liver transplantation Thesis, University of Groningen, the Netherlands E-publication available at https://epubs.ogc.nl/?epub=f.arshad ISBN (printed version): 978-94-6169-908-4 ISBN (electronic version): 978-94-6169-924-4 Copyright 2016 Freeha Arshad, the Netherlands All rights reserved. No parts of this thesis may be reproduced, stored in a retrieval system or transmitted in any form or by any means, without permission of the author. Cover design: Freeha Arshad Lay-out and printed by: Optima Grafische Communicatie, Rotterdam, the Netherlands

Pathophysiology and Management of Hemostatic Alterations in Cirrhosis and Liver Transplantation Proefschrift ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen op gezag van de rector magnificus prof. dr. E. Sterken en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op woensdag 7 september 2016 om 14.30 uur door Freeha Arshad geboren op 22 april 1984 te Amsterdam

Promotores Prof. dr. R. J. Porte Prof. dr. T. Lisman Copromotor Dr. M.T. de Boer Beoordelingscommissie Prof. dr. A.M.G.A. de Smet Prof. dr. J. Pirenne Prof. dr. K. Meijer

TABLE OF CONTENTS Chapter 1 General introduction and outline of this thesis 9 Part A. Hemostatic drugs in patients with cirrhosis Chapter 2 Infusion of DDAVP does not improve primary hemostasis in patients with cirrhosis Liver International. 2015;35:1809-1815. 21 Chapter 3 Differential in vitro inhibition of thrombin generation by anticoagulant drugs in plasma from patients with cirrhosis PlosOne. 2014;9:e88390; doi:10.1371/journal.pone.0088390. 35 Chapter 4 Routine coagulation assays underestimate levels of antithrombin-dependent but not of direct anticoagulant drugs in plasma from patients with cirrhosis British Journal of Haematology. 2013;163:666-673. 55 Part B. Blood loss and prevention of blood loss and RBC transfusion during liver transplantation Chapter 5 Physiology, prevention, and treatment of blood loss during liver transplantation In: Wagener G, editor. Liver Anesthesiology and Critical Care Medicine. Springer; 2012. p. 169-179. 73 Chapter 6 Red blood cell transfusion requirements during orthotopic liver transplantation have increased after market withdrawal of aprotinin Submitted for publication. 93 Chapter 7 Prothrombin complex concentrate in the reduction of blood loss during orthotopic liver transplantation: PROTON-trial BMC Surgery. 2013; 13: 22. 107

Chapter 8 Serum markers of portal hypertension are associated with blood loss and transfusion requirements during orthotopic liver transplantation Submitted for publication. 131 Part C. The hemostatic status of the liver transplant recipient Chapter 9 Hypercoagulability as a contributor to thrombotic complications in the liver transplant recipient Liver International. 2013;33:820-827. 145 Chapter 10 Abnormal hemostatic function one year after orthotopic liver transplantation can be fully attributed to endothelial cell activation F1000. 2014;3:103. doi:10.12688/f1000research.3980.2. 163 Chapter 11 Summary 181 Chapter 12 Discussion and future perspectives 189 Nederlandse samenvatting 205 List of publications 213 Dankwoord 219 Biography 201 List of abbreviations 229