Aspirin resistance and platelet turnover: A 25-year old issue

The evidence of an incomplete inhibition of platelet function by aspirin, despite therapeutic doses of the drug proved to be clinically effective are employed, was first reported in the ‘80s, in the frame of studies devoted to platelet turnover. Because inhibition of platelet aggregation by aspirin is irreversible, the return after an interval of time of the ability to form thromboxane by platelets in circulating blood should reflect the entry into the circulation of platelets whose cyclooxygenase activity has not been affected by aspirin. Based on this concept, the possibility of monitoring the entry of newly formed platelets into the circulation after aspirin ingestion was documented by measuring the return of thromboxane biosynthesis by platelets challenged in vitro by pairs of aggregating agents. The data obtained showed that platelets with intact cyclooxygenase activity could be detected into the circulation of control individuals as early as 4–6 h after aspirin ingestion, and at shorter time intervals in diabetic angiopathy. In the latter setting,the data allowed to conclude that “schedules of aspirin which may suffice in normals are not effective in patients with diabetic angiopathy, presumably because these patients have a high rate of entry of new platelets into the circulation”.