The Recovery of Platelet Cyclooxygenase Activity Explains Interindividual Variability in Responsiveness to Low-Dose Aspirin in Patients With and Without Diabetes.

Background: Interindividual variability in response to aspirin has been popularized as "resistance". We hypothesized that faster recovery of platelet cyclooxygenase-1 activity may explain incomplete thromboxane (TX) inhibition during the 24-hour dosing interval. Objective: Characterize the kinetics and determinants of platelet cyclooxygenase-1 recovery in aspirin-treated diabetic and non-diabetic patients. Patients/Methods: One-hundred type 2 diabetic and 73 non-diabetic patients on chronic aspirin 100 mg daily were studied. Serum TXB(2) was measured every 3 hours, between 12 and 24 hours after a witnessed aspirin intake, to characterize the kinetics of platelet cyclooxygenase-1 recovery. Patients with the fastest TXB(2) recovery were randomized to aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily, for 28 days and TXB(2) recovery was reassessed. Results and Conclusions: Platelet TXB(2) production was profoundly suppressed at 12 hours in both groups. Serum TXB(2) recovered linearly, with a large interindividual variability in slope. Diabetic patients in the third tertile of recovery slopes (≥0.10 ng/ml hr(-1) ) showed significantly higher mean platelet volume, body mass index, and younger age. Higher body weight was the only independent predictor of a faster recovery in non-diabetics. Aspirin 100 mg twice daily completely reversed the abnormal TXB(2) recovery in both groups. Interindividual variability in the recovery platelet cyclooxygenase activity during the dosing interval may limit the duration of the antiplatelet effect of low-dose aspirin in patients with and without diabetes. Inadequate thromboxane inhibition can be easily diagnosed and corrected by a twice daily regimen. © 2012 International Society on Thrombosis and Haemostasis.