Individual variation in the effects of ASA on platelet function: implications for the use of ASA clinically.
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OBJECTIVE: To determine whether acetylsalicylic acid (ASA) inhibits hemostasis and platelet function in some individuals (ASA responders) but not in others (ASA nonresponders). DESIGN: In this two-part study, part 1 was a randomized, double-blind crossover study of the effects of various single doses of ASA (80 to 1300 mg) on primary hemostasis and platelet function. Part 2 was a prospective cohort study of the effects of a chronic dose of ASA (325 mg) on primary hemostasis and platelet function. SETTING: A hospital research laboratory and a cardiac care ward. SUBJECTS: Part 1: 10 healthy volunteers (five male, five female). Part 2: 40 consecutive patients undergoing elective coronary artery bypass grafting (CABG). RESULTS: Part 1: ASA, in a dose-related manner, prolonged the bleeding time in 60% of volunteers (ASA responders), which was associated with decreases in platelet thromboxane (Tx) A2 and 12-hydroxyeicosatetraenoic acid (12-HETE) synthesis and in platelet aggregation and adhesion. However, in volunteers whose bleeding time was not prolonged (ASA nonresponders), platelet 12-HETE synthesis and platelet adhesion were unchanged or increased (P < 0.001), despite platelet TxA2 and platelet aggregation being inhibited. Part 2: similarly, 58% of the CABG patients were ASA responders and all of their platelet biochemistry and function tests were inhibited, while in the CABG patient ASA nonresponders (no prolongation of bleeding time), platelet 12-HETE and platelet adhesion were increased (P < 0.001).
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