Increased Thromboxane Metabolites Excretion in Liver Cirrhosis

Giovanni Davì; Domenico Ferro; Stefania Basili; Luigi Iuliano; Caterina Camastra; Carlo Giammarresi; Stella Santarone; Bianca Rocca; Raffaele Landolfi; Giovanni Ciabattoni; Corrado Cordova; Francesco Violi

doi:10.1055/s-0037-1615058

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 79(04): 747-751
DOI: 10.1055/s-0037-1615058

Rapid Communication

Schattauer GmbH

Increased Thromboxane Metabolites Excretion in Liver Cirrhosis

Giovanni Davì

¹From the Departments of Medicine, Universities of Chieti, Rome

,

Domenico Ferro

²From the Departments of Medicine, “La Sapienza”, Rome

,

Stefania Basili

²From the Departments of Medicine, “La Sapienza”, Rome

,

Luigi Iuliano

²From the Departments of Medicine, “La Sapienza”, Rome

,

Caterina Camastra

²From the Departments of Medicine, “La Sapienza”, Rome

,

Carlo Giammarresi

¹From the Departments of Medicine, Universities of Chieti, Rome

,

Stella Santarone

¹From the Departments of Medicine, Universities of Chieti, Rome

,

Bianca Rocca

³From the Departments of Medicine, Rome Catholic University, Italy

,

Raffaele Landolfi

³From the Departments of Medicine, Rome Catholic University, Italy

,

Giovanni Ciabattoni

⁴From the Departments of Medicine, Institute of Pharmacology, Catholic University of Rome, Italy

,

Corrado Cordova

²From the Departments of Medicine, “La Sapienza”, Rome

,

Francesco Violi

²From the Departments of Medicine, “La Sapienza”, Rome

› Author Affiliations

Abstract

Summary

An augmented systemic production of thromboxane (TX) A₂, as assessed by urinary excretion of the thromboxane metabolites, has been described in severe liver cirrhosis. However, the significance of this finding remains unclear since in liver cirrhosis a number of phenomena i.e. altered hepatic TXA₂ metabolism, increased intrasplenic platelet destruction, may affect TXA₂ entry into systemic circulation as well as its metabolism. In order to further clarify this, we measured both major 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 assayed with previously validated RIA techniques.

The urinary excretion rate of 11-dehydro-TXB₂ was significantly (p = 0.0001) increased in the cirrhotic patients (673.5 pg/mg cr, median) in comparison with the controls (275 pg/mg cr, median) but no significant difference could be demonstrated 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 controls (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 cr, median). The urinary excretion of 2,3 dinor-TXB₂ was significantly (p = 0.008) related to plasma prothrombin fragment 1+2 (F1+2).

This study provides further evidence of increased thromboxane biosynthesis in liver cirrhosis. Moreover, we demonstrate intraliver shift of thromboxane metabolic disposition, due to progressive liver decompensation, because only the fraction undergoing β-oxidation to 2,3-dinor-TXB₂ was 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 partly account for in vivo platelet activation.

Full Text

References

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