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Altered platelet function in cirrhosis of the liver: Impairment of inositol lipid and arachidonic acid metabolism in response to agonists
Author(s) -
Laffi Giacomo,
Cominelli Fabio,
Ruggiero Marco,
Fedi Sandra,
Chiarugi Vincenzo P.,
La Villa Giorgio,
Pinzani Massimo,
Gentilini Paolo
Publication year - 1988
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840080625
Subject(s) - platelet , arachidonic acid , medicine , thromboxane a2 , endocrinology , cirrhosis , thromboxane , phospholipase a2 , platelet activation , thrombin , chemistry , biochemistry , enzyme
Hemorrhagic disorders are common in patients with liver cirrhosis and result from several factors including impaired platelet function. We evaluated platelet aggregation and arachidonic acid metabolism in response to standard agonists in platelet‐rich plasma from 12 cirrhotic patients with mild impairment of liver function (Child A), 12 patients with severe liver dysfunction (Child B and C) and 12 healthy subjects. Platelet aggregation and thromboxane A 2 production were consistently reduced in patients with severe liver impairment. To determine whether the platelet dysfunction is due to an intrinsic platelet defect or a circulating inhibitor, we measured platelet aggregation and thromboxane A 2 synthesis on washed platelets in healthy subjects and in Child B and C patients. The aggregating response of washed platelets in response to thrombin, collagen and arachidonic acid was markedly reduced, suggesting an intrinsic platelet defect. The biochemical events underlying platelet aggregation were investigated by prelabeling platelets with [1‐ 14 C]arachidonie acid. Thrombin‐induced activation of phospholipase C (measured as the release of [1‐ 14 C]phosphatidic acid) and phospholipase A 2 (measured as the release of [1‐ 14 C]arachidonic acid and its metabolites) was greatly impaired in platelets from patients with severe liver impairment. We conclude that in advanced cirrhosis there is a severe reduction in platelet aggregatory response to physiologic agonists due to an intrinsic platelet defect which is related to an impairment of the platelet transmembrane signaling mechanism induced by receptor stimulation.