INHIBITION OF THROMBIN GENERATION BY ASPIRIN IS BLUNTED IN HYPERCHOLESTEROLEMIA

Recent evidence indicates that aspirin inhibits thrombin generation in clotting blood. We noticed that this effect was less pronounced in pa tients with hypercholesterolemia. The aim of the study was to prove th is observation. The effects of aspirin on thrombin generation were eva luated in (1) 46 healthy volunteers, 2 hours after ingestion of a sing le, 500-mg dose and (2) 28 survivors of myocardial infarction who took 300 mg aspirin/d for 2 weeks. In both populations. two well-matched s ubgroups were distinguished, using a serum cholesterol level of 6.2 mm ol/L (240 mg/dL) and an LDL cholesterol level of 4.0 mmol/L (155 mg/dL ) as borderline. Thrombin generation was monitored ex vivo in blood em erging from a skin microvasculature injury and additionally, in a sing le-dose study in vitro in recalcified plasma. Aspirin depressed thromb in generation in the group of subjects with serum cholesterol <6.2 mmo l/L and LDL cholesterol <4.0 mmol/L but not in the group with high blo od cholesterol levels. Inhibitory effects of aspirin were more pronoun ced after the 2-week treatment than after a single dose. There was a s ignificant correlation between total serum cholesterol or LDL choleste rol and total amount of thrombin generated after aspirin treatment. In subjects with high blood cholesterol levels, thrombin generation was not affected by aspirin. Blunting of aspirin action in hypercholestero lemia might be explained by (1) alterations in platelet lipid-protein matrix that render their membrane proteins less accessible for acetyla tion by aspirin and (2) changes in composition and structure of plasma lipoproteins that diminish the chance of aspirin to interact with pro thrombin.