Sarah Bos

12 CHAPTER 1 consistent on whether there is a hyper- or hypofibrinolytic state in patients with cirrhosis.(7,16–18) These differences might be explained by the variety in and poor reproducibility of assays on the fibrinolytic status in patients with cirrhosis. Hemostatic testing in liver disease Routine diagnostic tests of coagulation, such as prothrombin time (PT) and activated partial thromboplastin time (APTT), universally fail to test the hemostatic capacity of a blood sample, as these tests are only sensitive for plasma levels of procoagulant proteins. This is a particular concern in patients with liver diseases who have complex alterations in both pro- and anticoagulant pathways. The results of routine diagnostic tests of hemostasis, therefore have long been misinterpreted. Thrombomodulin-modified thrombin generation gives an accurate representation of the balance between pro- and anticoagulant factors. It has been shown that thrombin generation in patients with cirrhosis is equal or even better than that in healthy individuals, which contrasts sharply with the results from PT and APTT tests which are prolonged in patients.(14,19–22) Hemostatic complications in liver disease Patients with cirrhosis are vulnerable to both bleeding and thrombotic events. A relatively recent systematic review and meta-analysis showed in a cohort of 700.000 patients with cirrhosis and 1.5 million controls that patients with cirrhosis have a 1.7 fold increased risk of deep vein thrombosis and pulmonary embolism. (23) The prevalence of splanchnic vein thrombosis in patients with cirrhosis is 8 to 15%.(24,25) The incidence of venous thrombosis in cirrhosis correlates with the severity of the underlying disease.(26) Development of portal vein thrombosis increases the risk of disease deterioration and mortality.(26,27) In patients undergoing hepatobiliary surgery there is a prolonged hypercoagulable state with an increased risk of developing venous thombo-embolisms.(28) Bleeding complications in patients with cirrhosis are common, however many of the clinically relevant bleeds– i. e. variceal bleeds – are unrelated to hemostasis. These bleeding events are rather a signal of portal hypertension.(29) Anticoagulation in liver disease Low-molecular weight heparins (LMWH) are the standard-of-care treatment for portal vein thrombosis in cirrhosis. Patients with cirrhosis have substantially decreased levels of antithrombin impeding correct dosing. There is increasing enthusiasm for the use of direct oral anticoagulants (DOACs). These anticoagulants