Sarah Bos

106 CHAPTER 6 in OLT(18,22), and cirrhosis(26,41). In vitro and ex vivo studies have demonstrated little to no prohemostatic effect of FFP by thrombin generation tests in patients with cirrhosis(25,42). Although prophylactic administration of FFP in HPB surgery is common, and leads to improvement of routine laboratory parameters such as the INR, the actual prohemostatic effect of FFP is questionable. More importantly, FFP can lead to circulating volume overload which may increase bleeding risk by increasing portal and central venous pressure. Given the poor evidence that FFP is clinically effective in prophylactic and treatment settings(23,24), a search for alternative prohemostatic options would be wise. Our data suggest PCCs to be effective in improving hemostatic capacity during HPB surgery, although the exaggerated responses in our in vitro test may warrant careful dosing. The advantage of PCCs over FFP is that PCCs lead to a much more robust increase in coagulation factor levels, as PCCs contain highly concentrated coagulation factors in a small volume. Our results are in line with a single-center retrospective study of liver transplant recipients, which showed that the administration of PCCs and/or fibrinogen concentrate guided viabedsidehemostatic testingwas safe andeffective as compared to an FFP/platelet concentrate-based approach(43). In addition, an in vitro study in which plasma samples taken during OLT were supplemented with PCC or FFP showed a better improvement of thrombin generating capacity by PCCs as assessed by modern thrombin generation testing(44). Although our data indicate a possible requirement for dose-adjustments of commonly used pro- and anticoagulant strategies in the HPB patient, we acknowledge the limitations of our in vitro approach. Thrombin generation is thus far only used in a research setting. It is a relatively cumbersome test and not yet ready for clinical use, although the automated test (Genesia) has been launched and whole blood thrombin generation tests that may be suitable as a point-of-care test are in development. In addition, it is unknown which level of ETP represents the optimal pro- or anticoagulant status, and therefore we do not have ETP target levels for management of thrombosis or bleeding. To incorporate dose adjustments in further studies we would need such information to be able to adjust the dosing of pro- or anticoagulants in this specific population. Our study is limited by a relatively low sample size and heterogenous cohorts. Our OLT cohort contains a large proportion of patients with cholestatic liver disease, which are known to be more hypercoagulable compared to patients with cirrhosis of other etiologies(45). In addition, our partial hepatectomy cohort consists of patients with and without an underlying malignancy, and these patients also differ in their baseline hemostatic status. Although we did not detect obvious differences between patients in responses to pro- or anticoagulant agents in these subgroups, we note our cohorts are too small for meaningful subgroup analyses.