Sarah Bos

13 General introduction 1 are the recommended treatment for venous thromboembolism and atrial fibrillation in the general population.(30,31) DOACs have several advantages over vitamin K antagonists (VKA) and LMWH. The administration is in tablet form, with no requirement of laboratory monitoring. The evidence on the use of DOACs in cirrhosis patients is still very limited as they were excluded from the large phase III trials that evaluated the efficacy and safety of DOACs. Currently DOACs are still contraindicated in patients with advanced liver disease accompanied with coagulopathy and clinically relevant bleeding risk . Even though study sizes are quite small, current pharmacokinetic and in vitro studies show encouraging safety data, providing basis for further studies on the use of DOACs in cirrhosis.(32–34) Procoagulants in liver disease Treatment of bleeding complications in patients with cirrhosis traditionally are addressed as any other form of bleeding complication with the transfusion of packet cells, fresh frozen plasma (FFP), and sometimes even platelet concentrates guided by routine diagnostic test. The transfusion of large volumes may, in fact, be counterproductive as it leads to fluid overload and a increases portal venous pressure. Improving hemostasis guided via routine diagnostic potentially leads to the use of an overload of procoagulant products, which can lead to transfusion related complications.(35) Aim of this thesis The main focus of this thesis is gaining insight in potential differences of the hemostatic balance of all etiologies of cirrhosis and presenting the effects of currently available drugs that are indicated for preventing or treating thrombosis and bleeding in patients with liver disease and in patients undergoing hepato- pancreatico-biliary surgery (HPB-surgery). First this thesis will show an detailed study on the specific hemostatic status of cirrhosis and the different etiologies. Next the in vitro effect of the most commonly used anticoagulant and procoagulant drugs in patients with cirrhosis will be described. Furthermore the potency of one of the direct oral anticoagulant in cirrhosis will be described. In the second part of this thesis the emphasis is gaining insight in the hemostasis in HPB surgery. At first a detailed overview of the incidence and prevalence of hemostatic complications and the possible therapeutic options will be given, This will be followed by a trial on the in vitro effect of the mainly used pro- and anticoagulant therapies in HPB surgery.