REDUCED EXPRESSION OF THROMBOPOIETIN IS INVOLVED IN THROMBOCYTOPENIA IN HUMAN AND RAT-LIVER CIRRHOSIS

It is widely accepted that thrombocytopenia associated with liver cirr hosis is caused by increased platelet destruction in the enlarged sple en, but this issue has not yet been analysed sufficiently in terms of platelet production. Thrombopoietin is produced mainly in the liver an d strongly promotes platelet production. We studied serum thrombopoiet in and the levels of its mRNA in liver tissue of cirrhotic patients an d also in a rat model of liver cirrhosis. Furthermore, to clarify the influence of the spleen, we investigated thrombopoietin mRNA in splene ctomized rats. The serum thrombopoietin level in humans with liver cir rhosis was not significantly reduced instead of thrombocytopenia. The expression of thrombopoietin mRNA in liver tissue decreased with the p rogression of liver cirrhosis in both patients and the rat model and n o compensatory expression was observed in other organs or nonparenchym al cells. The level of thrombopoietin mRNA did not differ significantl y in splenectomized cirrhotic rats before or after administration of d imethylnitrosamine, but was lower than that in splenectomized rats wit hout cirrhosis. We conclude that thrombocytopenia in liver cirrhosis i s caused not only by platelet destruction but also by decreased platel et production, perhaps due to reduction of thrombopoietin mRNA in the liver.