Sarah Bos

102 CHAPTER 6 until day 6. Antithrombin levels were normal in patients at the start of surgery, but decreased during surgery and did not fully normalize until day 6 (supplementary figure 3). Patients generated more thrombin as compared to controls throughout the procedure, which is in contrast with our previously published data(19), in which we reported normal thrombin generation (Supplementary table 3). The pro-hemostatic drugs and anticoagulants that were tested in the samples from patients undergoing OLT and partial hepatectomy were also added to the samples taken from patients during and after PPPD. Absolute ETP levels in absence and presence of the pro- and anticoagulant drugs are shown in figure 5 and 6. Statistical differences indicated are differences in proportional change in ETP upon addition of pro- or anticoagulants between controls and patients. Supplementary table 3 shows absolute ETP values and percentual differences between ETP values in absence and presence of pro- or anticoagulant agents, with significance levels relative to the healthy control group. Addition of pooled normal plasma or rFVIIa had very little effect on total thrombin generation in patients and controls. In contrast, the addition of PCC increased thrombin generation to a similar extent in patients and controls, but total thrombin generation in the presence of PCC was much higher in patients as a result of elevated thrombin generation compared to controls in the absence of drug. The effects of the anticoagulants in the plasma of patients after PPPD are similar to the effect described in the patients after partial hepatectomy, with heparins and dabigatran exerting similar to increased anticoagulant potency in patients compared to controls, but with higher absolute ETPs in presence of drug in patients, particularly with LMWH. Rivaroxaban had very poor anticoagulant effects both in relative and absolute terms.

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