Sarah Bos

126 CHAPTER 7 in patients undergoing HPB-surgery, dosing of pro- or anticoagulant therapy is complicated. Better understanding of the efficacy of commonly used pro- and anticoagulant drugs is thereforewarranted. In chapter 6we assessed the efficacy of both pro- and anticoagulant drugs in plasma of patients undergoing HPB-surgery. (57) Patients undergoing HPB-surgery are hypercoagulable when assessed with thrombomodulin-modified thrombin generation testing. Assessment of the risk of bleeding or thrombosis in patients undergoing HPB-surgery is as difficult as in patients with cirrhosis. Although PT, platelet count, and an INR during or after the procedure may suggest a bleeding tendency, they do not appear to reflect the actual hemostatic status. As for patients with cirrhosis, patients undergoing HPB- surgery also have a higher risk of thrombosis with lower incidences of bleeding complications.(47,49,52,53,58,59) The commonly used anticoagulant drugs (LMWH, unfractionated heparin (UFH)) show slightly altered potencies in patients that undergo HPB-surgery. Especially of interest is the finding that standard dosages of LMWH and rivaroxaban suggest an insufficient anticoagulant effect, shown by an increased ETP compared to controls, in patients that undergo HPB-surgery. Next to enhanced thrombin generation it is also shown in chapter 6 that patients that underwent HPB-surgery more often have elevated levels of fibrinogen. Postoperative hypofibrinolysis (10) and a VWF/ADAMTS13 unbalance (60,61) may also contribute to the hypercoagulable state of these patients. Despite standard dosing of thromboprophylaxis the risk of VTE after partial hepatectomy is still increased.(47,49,54) Together with the data in this thesis, it might be suggested to increase the dose of thromboprophylaxis postoperatively. Increased dosages have been suggested in earlier studies, however, safety and efficacy of such an approach requires further study.(54,55) In specific clinical settings, such as orthopedic surgery, DOACs can be used as an alternative for LMWH as thromboprophylaxis. To date, the use of DOACs as thromboprophylaxis have not been extensively explored in general surgery, HPB- surgery or even in liver transplantation. A small phase 1 study showed that the concentration of rivaroxaban after bariatric surgery does not alter compared to values pre-operatively.(62) Clinical outcomes of rivaroxaban in this group are unfortunately not available. As described earlier, the main advantage of DOACs over LMWH is the mode of administration. DOACs also do not need to be monitored as for VKA and in some clinical settings LMWH as well. Besides, monitoring LMWH is troublesome after OLT and partial hepatectomy since antithrombin levels are frequently low with the risk of overdosing.(3,50,63) This thesis and previous in vitro studies show a substantially altered anticoagulant