Fibrin clot properties and thrombus composition in cirrhosis

Abstract

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 patients with cirrhosis. Patients with mild cirrhosis have increased thrombin generation capacity and plasma fibrinogen levels, which may be balanced by delayed fibrin polymerization and decreased factor XIII levels. With progressing illness, plasma fibrinogen levels decrease, but thrombin generation capacity remains elevated. Fibrinogen is susceptible 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 stability 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.

Keywords: cirrhosis; fibrin; fibrinogen; fibrinolysis; thrombosis.

Figure 1

Fibrin formation and fibrinogen properties in patients with cirrhosis. Created with BioRender. FXIII, factor XIII

Figure 2

Composition of nonmalignant portal vein thrombi in patients with cirrhosis. Top panels: MSB-stained section (left) of an extrahepatic portal vein thrombus showing intimal hyperplasia with some hemorrhage, but no fibrin. The scanning electron microscopy images of the same thrombus sample (middle and right images of the upper panel ) show collagen bundles, but no fibrin and few erythrocytes. Bottom panel: MSB-stained section (left) of a portal vein thrombus showing intimal hyperplasia with a fibrin-rich thrombus within the lumen of the vessel. The scanning electron microscopy images (middle and right images of the lower panel) show a fibrin mesh with erythrocytes entrapped. Note that most erythrocytes are in their biconcave shape and not in a polyhedral shape that is often observed in contracted blood clots or thrombi. MSB, Martius Scarlet Blue