Advanced cirrhosis is associated with reduced platelet function and altered renal function and sodium handling. Arachidonic acid (AA) metabolites contribute to platelet aggregation and to maintain the response to diuretics in advanced cirrhosis. In the present study, we tested the effects of a dietary supplementation for 8 weeks with a triacylglycerol (triglyceride) enriched in AA (ARASCO®; 4 g/day) or oleic acid (OA) on plasma and membrane fatty acid composition, platelet aggregation and renal prostaglandin (PG) metabolism. At baseline, all patients had reduced platelet aggregation. Patients treated with AA showed a significant increase in the percentage of AA in plasma lipids and membrane phospholipids. These changes were associated with an increased platelet aggregation in response to collagen (from 55.83±20.63 to 67.67±14.44%; P<0.05). At baseline, all urinary AA metabolites, including PGE2, 6-keto-PGF1α, 8-epi-PGF2α and 11-dehydro-thromboxane B2, were elevated in cirrhotic patients when compared with a group of normal subjects. After furosemide treatment, urinary excretion of 11-dehydro-thromboxane B2 increased significantly. Supplementation with AA did not result in any significant change in urinary PG excretion either before or after diuretic administration. The results of the present study show that dietary supplementation with AA effectively increases the levels of this fatty acid in plasma and membrane phospholipids and improves platelet aggregation. These data suggest a possible novel approach to the treatment of the haemostatic defect observed in these patients.
- platelet aggregation
- renal function
- © 2004 The Biochemical Society