Platelet lipid composition and platelet aggregation

Abnormal plasma lipoproteins in patients with liver disease are associated with an increase in erythrocyte cholesterol concentration and a raised erythrocyte cholesteroVphosphoEpid molar ratio. We hypothesized that their platelets would also have an increased cholesteroVphospholipid ratio and that this might affect aggregation in vitro. Platelet aggregation 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 cholesteroVphospholipid ratio was 13% higher in the patients and correlated closely with erythrocyte cholesteroVphospholipid ratio. Platelet aggregation was reduced in most of the patients and inversely correlated with the cholesteroVphospholipid 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 lecithidsphingomyelin 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.a 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.-Owen, J. S., R. A. Hutton, R. C. Day, K. R. Bruckdorfer, and N. McIntyre. Platelet lipid composition and platelet aggregation in human liver disease. J. Lipid Res. 1981. 22: 423-430. Supplementary key words arachidonic acid . membrane fluidity . platelet cholesterol * platelet phospholipids In many patients with liver disease erythrocyte cholesterol and phosphatidylcholine concentrations are increased and the cholesterol/phospholipid ratio is raised (1). T h e excess lipid is acquired from the abnormal plasma lipoproteins (2, 3) and the resulting decrease in membrane fluidity (4,5) is associated with an abnormal permeability to sodium (6) and with an enhanced ability of the cells to fuse in vitro in the presence of a chemical fusogen (7). We have suggested that similar membrane lipid changes may occur in other cells and affect their function (3). Incubation of platelets with cholesterol-rich liposomes increases their cholesterol content and their cholesterol/phospholipid molar ratio (8). These changes are accompanied by a decrease in membrane fluidity (9). The platelets of patients with Type IIa hyperlipoproteinemia also have a raised cholesterol/ phospholipid ratio (10). In both cases the platelets exhibit increased sensitivity to the aggregating agents ADP and adrenaline (8, 10). In this study we have tested the hypothesis that platelets from patients with liver disease might have an increased cholesteroYphospholipid ratio and that this might affect their ability to