Fibrin clot properties and thrombus composition in cirrhosis

Patients with cirrhosis frequently acquire profound hemostatic alterations, which may affect thrombus quality and composition-factors that determine the susceptibility to embolization and fibrinolysis. In this narrative review, we describe in vitro studies on fibrin clot formation and quantitative and qualitative changes in fibrinogen in patients with cirrhosis, and describe recent findings on the composition of portal vein thrombi in pa-tients with cirrhosis. Patients with mild cirrhosis have increased thrombin generation capacity and plasma fibrinogen levels, which may be balanced by delayed fibrin poly-merization and decreased factor XIII levels. With progressing illness, plasma fibrinogen levels decrease, but thrombin generation capacity remains elevated. Fibrinogen is sus-ceptible to posttranslational protein modifications and is, for example, hypersialylated and carbonylated in patients with cirrhosis. Despite changes in thrombin generation, factor XIII levels and the fibrinogen molecule, fibrin fiber thickness, and density are normal in patients with cirrhosis. Paradoxically, fibrin clot permeability in patients with cirrhosis is decreased, possibly because of posttranslational protein modifications. Most patients have normal fibrinolytic potential. We have recently demonstrated that portal vein thrombosis is likely a misnomer as the material that may obstruct the cirrhotic portal vein frequently consists of a thickened portal vein wall, rather than a true thrombus. Patients with cirrhosis often have thrombocytopenia and anemia, which may also affect clot sta-bility and composition, but the role of cellular components in clot quality in cirrhosis has not been extensively studied. Finally, we summarize abstracts on fibrin formation and clot quality that were presented at the ISTH 2022 meeting in London.

Automated summary

Patients with cirrhosis exhibit hemostatic alterations that affect clot quality and composition. In this review, we discuss in vitro studies on fibrin clot formation and changes in fibrinogen in cirrhosis patients. Additionally, we present recent findings on portal vein thrombi in cirrhosis patients. Thrombin generation capacity and plasma fibrinogen levels are increased in mild cirrhosis, but there is delayed fibrin polymerization and decreased factor XIII levels. As the disease advances, plasma fibrinogen levels decrease, but thrombin generation capacity remains elevated. Fibrinogen undergoes posttranslational protein modifications in cirrhosis patients. Fibrin clot permeability is decreased in cirrhosis patients, possibly due to these modifications. Most patients have normal fibrinolytic potential. Portal vein thrombosis in cirrhosis is often a misnomer, as it is often a thickened portal vein wall rather than a true thrombus. Platelet and anemia in cirrhosis may also impact clot stability and composition, but further research is needed. Finally, we summarize abstracts presented at the ISTH 2022 meeting in London on fibrin formation and clot quality.