INCREASED THROMBOXANE METABOLITES EXCRETION IN LIVER-CIRRHOSIS

An augmented systemic production of thromboxane (TX) A(2), as assessed by urinary excretion of the thromboxane metabolites, has been describ ed in severe liver cirrhosis. However, the significance of this findin g remains unclear since in liver cirrhosis a number of phenomena i.e. altered hepatic TXA(2) metabolism, increased intrasplenic platelet des truction, may affect TXA(2) entry into systemic circulation as well as its metabolism. In order to further clarify this, we measured both ma jor enzymatic metabolites of TXB2 in the urine of 44 patients affected by liver cirrhosis, subdivided in three classes on the basis of Child -Pugh criteria. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were assaye d with previously validated RIA techniques. The urinary excretion rate of 11-dehydro-TXB2 was significantly (p = 0.0001) increased in the ci rrhotic patients (673.5 pg/mg cr, median) in comparison with the contr ols (275 pg/mg cr, median) but no significant difference could be demo nstrated among the excretion rates of the three patient subgroups. The excretion rate of 2,3 dinor-TXB2 was also significantly (p = 0.0001) increased in the patients (824 pg/mg cr, median) in comparison with co ntrols (175 pg/mg cr, median), with a significant (p < 0.05) increase from class A (381 pg/mg cr) to class C (1337 pg/mg cr). The sum of the two enzymatic metabolites was significantly (p = 0.0001) increased in the cirrhotic patients in comparison to controls, with a progressive increase from class A (1003 pg/mg cr, median) to class C (2240 pg/mg c r, median). The urinary excretion of 2,3 dinor-TXB2 was significantly (p = 0.008) related to plasma prothrombin fragment 1+2 (F1+2). This st udy provides further evidence of increased thromboxane biosynthesis in liver cirrhosis. Moreover, we demonstrate intraliver shift of thrombo xane metabolic disposition, due to progressive liver decompensation, b ecause only the fraction undergoing beta-oxidation to 2,3-dinor-TXB2 w as progressively increased with the degree of liver failure. We, also, find a significant correlation between urinary excretion of 2,3-dinor -TXB2 and plasma F1+2, suggesting that clotting activation could partl y account for in vivo platelet activation.