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血清血栓素 B2 而非可溶性 P-选择素水平可识别阿司匹林治疗期间持续存在血小板反应性的缺血性脑卒中患者。

Serum thromboxane B2 but not soluble P-selectin levels identify ischemic stroke patients with persistent platelet reactivity while on aspirin therapy.

机构信息

Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bengaluru, India.

Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bengaluru, India.

出版信息

Thromb Res. 2021 Dec;208:92-98. doi: 10.1016/j.thromres.2021.10.021. Epub 2021 Oct 28.

DOI:10.1016/j.thromres.2021.10.021
PMID:34742142
Abstract

BACKGROUND

Aspirin non-response due to persistent platelet reactivity has been associated with adverse vascular events. Light transmission aggregometry (LTA), the 'gold standard' for measuring the platelet response to aspirin therapy, is a cumbersome procedure and a simple and reliable alternative is required. Our aim was to explore whether serum thromboxane B2 (sTXB2) and soluble P-selectin can be used to identify patients who are at risk of increased platelet reactivity while on aspirin.

METHODS AND RESULTS

We recruited 293 ischemic stroke patients, taking aspirin for more than seven days, and performed LTA to classify them. Based on therapeutic serum salicylate levels, 63 patients were excluded due to suspected non-compliance, followed by ELISA measurement of TXB2 and P-selectin in serum. Accordingly, patients were classified into 'Responders' (n = 122, 53%), 'Semi-responders' (n = 76, 33%) and 'Non-responders' (n=32, 14%) by LTA. Patients who had platelet aggregation of ≥70% with 10μM ADP and ≥20% with 0.5mM AA were defined as 'Non-responders'. In comparison with 'Responders', 'Non-responders' had 8.63-fold increased risk of secondary vascular events (p = 0.008). ROC curve analysis revealed that sTXB2, at a cut-off level of >4.15 ng/mL, could distinguish the patient group with elevated platelet reactivity with a sensitivity of 84.3% (AUC = 0.84), and was in fair agreement with the LTA-based classification of patients. Soluble P-selectin levels, on the other hand, had no discriminatory ability.

CONCLUSION

We suggest sTXB2 measurement as an alternative to the LTA approach for identifying aspirin-treated ischemic stroke patients who are at risk of enhanced platelet reactivity and subsequent vascular events.

摘要

背景

由于血小板反应性持续存在导致的阿司匹林无反应与不良血管事件有关。光传输聚集测定(LTA)是测量阿司匹林治疗中血小板反应的“金标准”,但该方法繁琐,需要一种简单可靠的替代方法。我们的目的是探讨血清血栓素 B2(sTXB2)和可溶性 P 选择素是否可用于识别阿司匹林治疗中血小板反应性增强的高危患者。

方法和结果

我们招募了 293 例缺血性脑卒中患者,这些患者服用阿司匹林超过 7 天,并进行 LTA 分类。根据治疗性血清水杨酸盐水平,排除了 63 例疑似不依从的患者,随后进行了血清 TXB2 和 P-选择素的 ELISA 测量。因此,根据 LTA 将患者分为“反应者”(n=122,53%)、“半反应者”(n=76,33%)和“无反应者”(n=32,14%)。血小板聚集率≥70%的患者用 10μM ADP 和≥20%的患者用 0.5mM AA 定义为“无反应者”。与“反应者”相比,“无反应者”发生二次血管事件的风险增加了 8.63 倍(p=0.008)。ROC 曲线分析显示,sTXB2 在>4.15ng/mL 时可以区分血小板反应性升高的患者,其敏感性为 84.3%(AUC=0.84),与基于 LTA 的患者分类具有良好的一致性。相比之下,可溶性 P 选择素水平没有鉴别能力。

结论

我们建议采用 sTXB2 测量作为替代 LTA 的方法,用于识别阿司匹林治疗的缺血性脑卒中患者,这些患者存在增强的血小板反应性和随后发生血管事件的风险。

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