Faculty of Pharmacy, Hôpital du Sacré-Cœur de Montréal, Montréal, Canada.
Int J Cardiol. 2011 Jul 1;150(1):39-44. doi: 10.1016/j.ijcard.2010.02.025. Epub 2010 Mar 7.
Platelets, long believed to be incapable of de novo protein synthesis, may retain their ability to form the cyclooxygenase (COX) enzyme once it has been inactivated by aspirin. This may explain the inefficacy of the drug to induce sustained platelet inhibition in certain patients. We evaluated the stability of platelet inhibition following once-daily enteric-coated aspirin administration.
Platelet responsiveness to aspirin was evaluated in 11 stable coronary artery disease patients on chronic aspirin therapy before and 1, 3, 8, and 24h after observed ingestion of 80-mg enteric-coated aspirin. Inhibition of the COX pathway was measured pharmacologically through plasma thromboxane (Tx) B(2) levels, and functionally by light transmission aggregometry in response to arachidonic acid. COX-independent platelet activity was measured in response to adenosine diphosphate, epinephrine and collagen.
Plasma TxB(2) levels showed profound inhibition of TxA(2) formation, which was stable throughout 24h, in all but 1 subject. This subject had optimal response to aspirin (inhibition of platelet TxA(2) production within 1h), but recovered the ability to synthesize TxA(2) within 24h of aspirin ingestion. Arachidonic acid-induced platelet aggregation closely mirrored TxB(2) formation in this patient, portraying a functional ability of the platelet to aggregate within 24h of aspirin ingestion. COX-independent platelet aggregation triggered TxA(2) production to a similar extent in all patients, likely through signal-dependent protein synthesis.
COX-dependent platelet activity is recovered in certain individuals within 24h of aspirin administration. Further research should consider increasing aspirin dosing frequency to twice daily, to allow sustained inhibition in such subjects.
长期以来，血小板被认为不能从头合成蛋白质，但一旦被阿司匹林失活，它可能仍然能够形成环氧化酶（COX）酶。这可能解释了为什么在某些患者中，阿司匹林不能有效地诱导持续的血小板抑制。我们评估了每日一次肠溶阿司匹林给药后血小板抑制的稳定性。
在 11 名稳定型冠状动脉疾病患者接受慢性阿司匹林治疗的情况下，在观察到服用 80mg 肠溶阿司匹林后 1、3、8 和 24 小时，评估了阿司匹林对血小板的反应性。通过测量血浆血栓素（Tx）B2 水平，通过光传输聚集测定法测量对花生四烯酸的反应性，从药理学上评估 COX 途径的抑制。通过对腺苷二磷酸、肾上腺素和胶原的反应，测量 COX 非依赖性血小板活性。
除 1 例患者外，所有患者的血浆 TxB2 水平均显示出对 TxA2 形成的强烈抑制，这种抑制在 24 小时内保持稳定。该患者对阿司匹林的反应最佳（在 1 小时内抑制血小板 TxA2 生成），但在服用阿司匹林后 24 小时内恢复了合成 TxA2 的能力。在该患者中，花生四烯酸诱导的血小板聚集与 TxB2 形成非常相似，表现出在服用阿司匹林后 24 小时内血小板聚集的功能能力。在所有患者中，COX 非依赖性血小板聚集引发 TxA2 生成的程度相似，可能通过信号依赖性蛋白质合成。
在某些个体中，COX 依赖性血小板活性在服用阿司匹林后 24 小时内恢复。进一步的研究应考虑增加阿司匹林的给药频率至每日两次，以允许在这些患者中持续抑制。
