Sarah Bos

105 Efficacy of pro- and anticoagulant strategies in plasma 6 clinical observations onmild bleeding inmany patients, even those with preexisting liver failure(18), and confirms thrombotic risk following HPB surgery(7–11,32). We also demonstrated altered potency of commonly used anticoagulant drugs with comparable to enhanced anticoagulant effects for UFH, LMWH and dabigatran, and profoundly decreased anticoagulant effects of rivaroxaban. Despite the increased anticoagulant effects of dabigatran and heparins, absolute on-drug thrombin generation was higher in patients compared to controls, particularly in case of LMWH. The anticoagulant effect of rivaroxaban was substantially lower in patients compared to controls with on-drug thrombin generation levels that substantially exceeded off-drug thrombin generation in controls. Our results therefore suggest an insufficient anticoagulant effect of standard dosages of LMWH and rivaroxaban in patients that undergo HPB surgery. Finally, we found no appreciable procoagulant effects of FFP and rFVIIa in patients and controls, but significant procoagulant activity of PCCs. The relative prohemostatic effect of PCCs appeared to be higher in liver transplant recipients compared to controls. We also found elevated fibrinogen levels, mainly after oncological surgery, which could be considered as an additional thrombotic risk factor(33,34). In light of the published data on increased risk of VTE after partial hepatectomy in the presence of optimal thrombosis prophylaxis with LWMH(7,8,11) and our current data, it may be justified to increase the LMWH dose early after HPB surgery, although clinical studies are requires to assess safety and efficacy of such an approach. Dose-adjustments have been previously proposed for patients undergoing partial hepatectomy(1,11), but no clinical studies have yet assessed this approach. Besides enhanced thrombin generation and hyperfibrinogenemia, patients that underwent HPB surgery are characterized by a persistent postoperative hypofibrinolysis(35) and a VWF/ADAMTS13 unbalance(36,37), which further contribute to the hypercoagulable state of these patients. Direct oral anticoagulants (DOACs) are replacing LMWH in thromboprophylaxis after orthopedic surgery, but use of DOACs in other surgical settings has not been extensively explored. The major advantage of DOACs over LMWH is the mode of administration, and an additional advantage in the HPB surgery setting is the independence of antithrombin, which is frequently low after OLT and major partial hepatectomy. However, given the substantially altered anticoagulant effects of the Xa-directed DOAC rivaroxaban, and the IIa-directed DOAC dabigatran, careful use is warranted in clinical application of these drugs in the surgical HPB setting, preferably guided by well-designed clinical studies. Our data on prohemostatic strategies show that rFVIIa and FFP have little to no in vitro prohemostatic effect. These results are in line with clinical data on the use of rFVIIa inHPB surgery(40), andwith increasing data arguing against liberal use of FFP