Platelet lipid composition and platelet aggregation in human liver disease

Abnormal plasma lipoproteins in patients with liver disease are associated with an increase in erythrocyte cholesterol concentration and a raised erythrocyte cholesterol/phospholipid molar ratio. We hypothesized that their platelets would also have an increased cholesterol/phospholipid ratio and that this might affect aggregation in vitro. Platelet aggregates by adrenaline and ADP was measured in 34 patients with a variety of liver diseases and in 20 normal subjects and the values were related to platelet lipid composition. The platelet cholesterol/phospholipid ratio was 13% higher in the patients and correlated closely with erythrocyte cholesterol/phospholipid ratio. Platelet aggregation was reduced in most of the patients and inversely correlated with the cholesterol/phospholipid ratio. Cross-incubation and hemostasis studies indicated that there were no inhibitory factors present in the plasma; the defect was in the platelets. In contrast, other workers have shown that cholesterol-rich platelets, either from patients with Type IIa hyperlipoproteinemia or prepared in vitro, aggregate more readily than normal platelets. However, the phospholipid and fatty acid compositions of our patient platelets were also abnormal: the lecithin/sphingomyelin ratio was increased and was inversely correlated with aggregation; the proportion of arachidonic acid was decreased and positively correlated with the aggregation. In our patients with liver diseases the effects of the altered phospholipid and fatty acid composition presumably overrode those of the increased cholesterol content so that instead of enhanced aggregation, only reduced or normal aggregation was seen. We conclude that the reduced platelet aggregation seen in liver disease may reflect a decrease in arachidonic acid availability for prostaglandin and/or thromboxane production.