Sarah Bos

88 CHAPTER 6 Abstract Background : in vitro efficacy of pro- and anti-hemostatic drugs is profoundly different in patients with compensated cirrhosis and in those who have cirrhosis and are critically ill. Objectives: Here we assessed the efficacy of pro- and anticoagulant drugs in plasma of patients undergoing hepato-pancreato-biliary (HPB) surgery, which is associated with unique hemostatic changes. Methods : we performed in vitro analyses on blood samples of 60 patients under- going HPB surgery and liver transplantation: 20 orthotopic liver transplantation (OLT), 20 partial hepatectomies and 20 pylorus-preserving pancreaticoduodenec- tomies (PPPD). We performed thrombin generation experiments before and after in vitro addition of fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), recombinant factor VIIa (rFVIIa), low-molecular weight heparin (LMWH), un- fractionated heparin, dabigatran, and rivaroxaban. Results : we showed that patients undergoing HPB surgery are in a hypercoagulable state by thrombin generation testing. FFP and rFVIIa had minimal effects on thrombin generation, whereas PCC had a more pronounced procoagulant effect in patients compared to controls. Dabigatran showed a more pronounced anticoagulant effect in patients compared to controls while rivaroxaban and LMWH had a decreased anticoagulant effect in patients. Conclusion : we demonstrate profoundly altered in vitro efficacy of commonly used anticoagulants, in patients undergoing HPB surgery as compared to healthy controls, which may have implications for anticoagulant dosing in the early post- operative period. In the correction of perioperative bleeding complications, PCCs appear much more potent than FFP or rFVIIa, and PCCs may require conservative dosing and caution in use in patients undergoing HPB surgery.