The recovery of platelet cyclooxygenase activity explains interindividual variability in responsiveness to low-dose aspirin in patients with and without diabetes
The recovery of platelet cyclooxygenase activity explains interindividual variability in responsiveness to low-dose aspirin in patients with and without diabetes
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DOI：
10.1111/j.1538-7836.2012.04723.x
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发表时间：
2012-07-01
影响因子：
10.4
通讯作者：
Patrono, C.
中科院分区：
文献类型：
--
作者：
Rocca, B.;Santilli, F.;Patrono, C.
另见Lordkipanidze M，Harrison P.阿司匹林一天两次保持新的考克斯-1在海湾。本书第12179页。摘要背景。个体间对阿司匹林反应的差异被认为是抵抗。我们假设，血小板环氧合酶-1活性的快速恢复可能解释在24小时给药间隔期间血栓素（TX）抑制不完全。Objective.研究阿司匹林治疗的糖尿病和非糖尿病患者血小板环氧合酶-1恢复的动力学和决定因素。患者/方法研究了100例2型糖尿病患者和73例非糖尿病患者，长期服用阿司匹林100 mg/d。观察阿司匹林摄入后12 ~ 24 h，每3 h测量一次血清TXB 2，以表征血小板环氧合酶-1恢复的动力学。TXB 2恢复最快的患者随机接受阿司匹林100 mg每日一次、200 mg每日一次或100 mg每日两次治疗28天，并重新评估TXB 2恢复情况。结果和结论。血小板TXB_2的产生在12小时在两组中被深深地抑制。血清TXB_2恢复呈线性，斜率个体间变异较大。恢复斜率第三个三分位数（= 0.10 ng mL-1 h-1）的糖尿病患者显示平均血小板体积和体重指数显著较高，且年龄较小。较高的体重是非糖尿病患者恢复较快的唯一独立预测因素。阿司匹林100 mg每日2次完全逆转两组TXB 2的异常恢复。给药间隔期间血小板环加氧酶活性恢复的个体间差异可能会限制低剂量阿司匹林对糖尿病患者和非糖尿病患者抗血小板作用的持续时间。血栓素抑制不足可以很容易地测量和纠正，每天两次的方案。
See also Lordkipanidze M, Harrison P. Aspirin twice a day keeps new COX-1 at bay. This issue, pp 12179. Summary 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-h dosing interval. Objective. To 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 TXB2 was measured every 3 h, between 12 and 24 h after a witnessed aspirin intake, to characterize the kinetics of platelet cyclooxygenase-1 recovery. Patients with the fastest TXB2 recovery were randomized to aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily, for 28 days and TXB2 recovery was reassessed. Results and Conclusions. Platelet TXB2 production was profoundly suppressed at 12 h in both groups. Serum TXB2 recovered linearly, with a large interindividual variability in slope. Diabetic patients in the third tertile of recovery slopes (= 0.10 ng mL-1 h-1) showed significantly higher mean platelet volume and 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 TXB2 recovery in both groups. Interindividual variability in the recovery of 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 measured and corrected by a twice daily regimen.