Sarah Bos

66 CHAPTER 5 Hemostatic changes during and after hepatobiliary surgery Patients undergoing hepatobiliary surgery may have an intact hemostatic system before the procedure, for example, patients requiring a partial hepatectomy for metastasized colon cancer, or patients with a metabolic disorder requiring liver transplantation. However, frequently the hemostatic function is already substantially compromised, such as patients with cirrhosis requiring partial hepatectomy or liver transplantation. The hemostatic changes of patients with cirrhosis have been reviewed extensively elsewhere.(11–13) In short, despite alterations in routine indices of hemostasis such as the platelet count and the prothrombin time (PT), patients with cirrhosis appear to be in hemostatic balance due to a concomitant decline in pro- and antihemostatic drivers.(13) During hepatobiliary surgery, substantial (additional) changes in the hemostatic system occur. These are likely due to a combination of factors. On the one hand, there is consumption induced by surgical damage and reperfusion injury during liver transplantation, hemodilution, decreased or absent synthesis of liver-derived hemostatic components following partial hepatectomy or during the anhepatic phase of liver transplantation.(14,15) On the other hand, there is a decreased or absent clearance of activated hemostatic proteins when functional liver volume becomes compromised.(14,15) Such changes lead to further abnormalities in routine diagnostic tests of hemostasis. We will summarize new insights into the development of hemostatic abnorm- alities during partial hepatectomy and liver transplantation below. Primary Hemostasis The platelet count decreases during and after partial hepatectomy and liver transplantation, reaching a nadir around day 3, after which it rapidly increases to supraphysiological levels.(16–18) An imbalance in the von Willebrand factor (VWF)/ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) axis has been suggested to compensate (in part) for the thrombocy- topenia of cirrhosis and acute liver failure.(19,20) A similar mechanism likely acts during and after partial hepatectomy and liver transplantation, as high VWF, low ADAMTS13, and enhanced VWF-dependent in vitro platelet adhesion have been observed in plasma samples taken during and after both procedures. (21–23) High levels of VWF likely relate to endothelial cell activation, whereas decreased ADAMTS13 is likely due to a combination of hemodilution, consumption, and decreased hepatic synthesis. The imbalanced VWF/ ADAMTS13 axis may not only compensate for the thrombocytopenia during these procedures but may contribute to thrombotic risk.(24) Indeed, imbalanced VWF/ADAMTS13 has been shown to be a risk factor for arterial thrombosis in the general population. (25,26) Interestingly, a VWF/ADAMTS13 imbalance also develops during pancreas resection,(22) although to a lesser extent as compared with the imbalance