Sarah Bos

120 CHAPTER 7 In this thesis, the hemostatic system of patients with cirrhosis has been studied in detail. Next to this, in vitro and in vivo studies of anticoagulation in cirrhosis have been performed. Finally, in collaboration with Kings College Hospital in London, in vitro studies on the effect of pro-and anticoagulant therapies have been performed in the plasma of liver transplant, and hepato-pancreatico-biliary (HPB) surgery patients. Patients with cirrhosis are at risk for both bleeding and thrombotic complications, andthesecomplicationsmayeitheroccur spontaneouslyorassociatedwith invasive procedures. In clinical practice, physicians often struggle with the indication for and dosages of both pro- and anticoagulant therapy in patients with cirrhosis to prevent or treat bleeding or thrombosis. Although high quality evidence is lacking, there is a need for clinical guidance for prevention and treatment of bleeding and thrombosis. Such guidance includes indications for treatment, drug of choice, and adequate dosing of these drugs. Importantly, treatment advice is complicated by possible alterations in drug efficacy and alterations in clearance of drugs. To come to a rational treatment advice, we first need to know whether the heterogenous group of patients with cirrhosis have uniform alterations on a hemostatic level. In chapter 2, an in-depth hemostatic profiling of primary hemostasis, secondary hemostasis and fibrinolysis was performed in a group of patients with mild cirrhosis associated with various underlying etiologies. Hemostatic profiles in cirrhosis The results in chapter 2 suggest that patients with Child-Turcotte-Pugh (CTP) A/B cirrhosis have an increased risk for thrombotic complications indicated by their prohemostatic state. These results are regardless of their etiology and once again this reinforces the altered balance in hemostasis in patients with cirrhosis.(1–3) Increasing evidence emerges that confirm that patients with cirrhosis have an increased risk for thrombotic events, notably venous thrombosis and portal vein thrombosis.(4–6) Literature on thrombin generation in cirrhosis varies. Whereas some studies show normal thrombin generating capacity, others reported increased levels of thrombin generation. One of the first papers to address the altered balance in cirrhosis is the key paper of Tripodi, which showed normal levels of thrombin generation in patients with cirrhosis.(7) Follow-up studies from other laboratories showed slightly different results. In these studies patients with cirrhosis regardless of their disease severity, expressed by MELD or CTP-score, are all characterized by increased thrombin generating capacity.(5,8–12) These results stress that patients with cirrhosis are not solely at risk for bleeding complications because of the often prolonged prothrombin time (PT) and low platelet levels .