Platelet Function in Experimental Models of Liver Cirrhosis

(1) Background: Platelet function is commonly altered in liver cirrhosis. In experimenta models of liver cirrhosis we have analyzed the mechanisms of this defective function. (2) Methods: Experiments were performed in a model of liver cirrhosis by bile duct-ligation in washed platelets by means of fluorescence spectroscopy with fura-2. (3) Results: We have found several alterations compatible with the existence of a hyperaggregatory state. These alterations are related to a defective platelet calcium handling, specifically to an enhanced intracellular calcium release evoked by thrombin and an increased amount of calcium stored in the intracellular organelles and are present before the appearance of ascites. Homocysteine plays a role in this enhanced platelet aggregation response, probably through an enhanced formation of reactive oxygen species, which is prevented by Folic acid pretreatment. Bile acids show a tendency to reduce calcium movements across platelet membranes which would reduce this hyperaggregatory state characterisitic of the non-ascitic phase of the disease. (4) Conclusions: In experimental models of liver cirrhosis, we have found platelet function alterations related to an increased calcium release secondary to an increased amount of calcium stored in the intracellular organelles. These alterations are related to a higher homocysteine sensitivity that induces an enhanced production of reactive oxygen species. Chronic treatment with folic acid eliminates those alterations, and it can be of interest to minimize risks associated with thrombotic events in cirrhosis.