Sarah Bos

127 General discussion 7 effect of several DOACs.(16,64) Before any clinical application of these drugs in the prevention or treatment of VTE’s can be recommended, further efficacy, safety and dose finding studies are warranted. Data on procoagulant therapy in HPB-surgery patients is quite clear, there is no increase in coagulation potential, assessed by thrombin generation tests, after the administration of fresh frozen plasma (FFP) and recombinant factor VIIa (rFVIIa) in patients and controls. There is however a significant procoagulant effect of prothrombin complex concentrate (PCC) on thrombin generation in patients undergoing liver transplantation.(65,66) A previous study on the use of rFVIIa in HPB-surgery patients show similar results.(67) There is surmounting data against the use of FFP in patients with cirrhosis and in patients undergoing OLT.(68–71) There is almost no prohemostatic effect of FFP shown by thrombin generation in patients with cirrhosis.(72,73) Although it may lead to the normalization of routine coagulation parameters such as the INR, the actual effect of FFP on hemostasis is questionable. It has to be noted that the administration of FFP can have possible side effects such as volume overload leading to an increased portal pressure and an increased risk of bleeding events. The clinical effect of FFP on hemostasis has little to no evidence, in this light alternative prohemostatic options should be explored.(74,75) PCCmight be a suitable option as an alternative to FFP. The data of chapter 6 shows that PCC is effective in improving hemostatic capacity in HPB-surgery patients. Additionally PCC has a highly concentrated amount of coagulation factors in a small volume. The exaggerated in vitro response of PCC seen in chapter 6 might warrant careful use and dosing of these drugs. Earlier thrombin generation testing supports the use of PCC versus FFP in samples taken from patients during OLT (66). The in vitro approach in chapter 6 limits extrapolation of our results to the clinical in vivo setting. Thrombin generation is only used for research settings. There is no data on which level of ETP represents the optimal value for anticoagulation or procoagulation in a patient. Bed side testing of hemostasis would further facilitate implementation of new anti- and procoagulant strategies. To date there is only one study on whole blood bed side testing and one study on automated thrombin generation.(76,77) Clinical implications of these findings need to be explored in further larger studies.