Relationship between Platelet Membrane Lipid Compositions and Platelet Aggregability in Alcoholic Liver Disease

Abstract

We studied the relationship between changes in platelet aggregability and platelet membrane lipid in alcoholic liver disease. The maximal rate of ADP‐induced platelet aggregation was significantly increased in the alcoholic liver disease group than in the control group. No significant difference was observed in the maximal rate of collagen‐induced platelet aggregation. However, a lag time required for the start of platelet aggregation was significantly shortened in the alcoholic liver disease group, indicating increased platelet aggregability. Results of the platelet aggregation test suggested that alcoholic liver disease patients have their platelet aggregation affected by the abnormality of prostaglandin metabolism. The alcoholic liver disease group was further divided into two subgroups: the hyperaggregation group and the unchanged aggregation group. Both free cholesterol and phospholipid in the platelet membrane were significantly increased in the alcoholic liver disease group. In phospholipid compositions, phosphatidylserine plus phosphatidylinositol were significantly decreased in the alcoholic liver disease group, whereas a significant decrease in phosphatidylserine plus phosphatidylinositol was observed in the hyperaggregation group of alcoholic liver disease. Analysis of fatty acid compositions of platelet membrane showed significantly decreased palmitic acid in the alcoholic group. There was no significant change of arachidonic acid, which directly affects platelet aggregation. Eicosapentaenoic acid significantly decreased in the alcoholic liver disease group, but there was no difference in docosahexaenoic acid. Meanwhile, the thrombogenic index, calculated from the fatty acids of platelet membrane, showed no difference between the alcoholic liver disease group and the control group. However, the thrombogenic index was significantly increased in the hyperaggregation group than in the unchanged aggregation group. These data suggested that platelet aggregation is affected by not only a change in arachidonic acid, but also changes in fatty acid compositions of the platelet membrane.

The use of recombinant factor VIIa in liver diseases

“…Defective platelet aggregation and reduced platelet production of thromboxane-A2, a metabolite of arachidonic acid, are common findings in patients with cirrhosis [30], along with storage pool deficiency and abnormalities of the platelet GPIIb [31,32] Although both free cholesterol and phospholipids in platelet membranes are increased and palmitic acid is decreased in alcoholic liver disease, no significant changes in arachidonic acid has been observed [33]. Elevated platelet-activating factor (PAF) levels were found in human cirrhotic livers when compared with noncirrhotic tissues, thus confirming previous results obtained in experimental animal models of cirrhosis [34,35].…”

Severe Prolongation of the INR in Spur Cell Anemia of Cirrhosis: True-True and Related?

“…Smeets et al also found cholesterol to increase the activity of lipid vesicles, with a composition mimicking the outer leaflet of the plasma membrane of the activated platelet (16). Further support is provided by Watanabe et al, who showed that among patients with alcoholic liver disease, increased cholesterol in platelet membranes correlates with hyperaggregation (17). We hypothesize that although patients with spur cell anemia have advanced liver disease with low production of extrinsic pathway clotting factors, they may actually be hypercoagulable, causing an absence of bleeding despite elevation of the PT-INR.…”

Comparative Effects ofα-,β-, andγ-Carbolines on Platelet Aggregation and Lipid Membranes

“…The present results suggest that platelet hypoaggregability might be induced in smokers and alcoholics by γ - and β -carbolines. However, the influences of cigarette smoking and alcohol consumption on platelet aggregation have been conflicting, with some studies reporting a reduction of aggregability [ 1 – 7 ] but others an enhancement of aggregability [ 8 – 11 ]. In contrast to fluid membranes (with increased fluidity) induced by AD γ C and AM γ C, rigid membranes (with decreased fluidity) show the enhanced platelet aggregability in response to epinephrine and thrombin [ 40 , 41 ].…”

“…While the enhanced platelet aggregability could be found in chronic smokers, subjects who had smoked 10 ± 2 cigarettes per day for 7–10 years showed the decreased fluidity of platelets, which was due to an increase of cholesterol in platelet membranes [ 58 ]. Platelet aggregability in response to ADP and collagen was enhanced in alcoholics with increasing cholesterol in platelet membranes [ 11 ]. The conflicting phenomena, hypoaggregability and hyperaggregability, associated with cigarette smoking and alcohol consumption appear to be explained by the biphasic effects of membrane fluidity changes.…”

“…The platelets of alcoholics are initially hypoaggregable but become hyperaggragable after the cessation of drinking [ 10 ]. ADP-induced platelet aggregation is increased in alcoholics [ 11 ].…”