Khan Hamzah, Gallant Reid C, Zamzam Abdelrahman, Jain Shubha, Afxentiou Sherri, Syed Muzammil, Kroezen Zachary, Shanmuganathan Meera, Britz-McKibbin Philip, Rand Margaret L, Ni Heyu, Al-Omran Mohammed, Qadura Mohammad
Division of Vascular Surgery, St. Michael's Hospital, Toronto, ON M4B 1B3, Canada.
Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON M4B 1B3, Canada.
Diagnostics (Basel). 2020 Oct 26;10(11):871. doi: 10.3390/diagnostics10110871.
Acetylsalicylic acid (ASA), also known as aspirin, appears to be ineffective in inhibiting platelet aggregation in 20-30% of patients. Light transmission aggregometry (LTA) is a gold standard platelet function assay. In this pilot study, we used LTA to personalize ASA therapy ex vivo in atherosclerotic patients. Patients were recruited who were on 81 mg ASA, presenting to ambulatory clinics at St. Michael's Hospital ( = 64), with evidence of atherosclerotic disease defined as clinical symptoms and diagnostic findings indicative of symptomatic peripheral arterial disease (PAD), with an ankle brachial index (ABI) of <0.9 ( = 52) or had diagnostic features of asymptomatic carotid arterial stenosis (CAS), with >50% stenosis of internal carotid artery on duplex ultrasound ( = 12). ASA compliance was assessed via multisegmented injection-capillary electrophoresis-mass spectrometry based on measuring the predominant urinary ASA metabolite, salicyluric acid. LTA with arachidonic acid was used to test for ASA sensitivity. Escalating ASA dosages of 162 mg and 325 mg were investigated ex vivo for ASA dose personalization. Of the 64 atherosclerotic patients recruited, 8 patients (13%) were non-compliant with ASA. Of ASA compliant patients ( = 56), 9 patients (14%) were non-sensitive to their 81 mg ASA dosage. Personalizing ASA therapy in 81 mg ASA non-sensitive patients with escalating dosages of ASA demonstrated that 6 patients became sensitive to a dosage equivalent to 162 mg ASA and 3 patients became sensitive to a dosage equivalent to 325 mg ASA. We were able to personalize ASA dosage ex vivo in all ASA non-sensitive patients with escalating dosages of ASA within 1 h of testing.
乙酰水杨酸(ASA),又称阿司匹林,在20%至30%的患者中似乎无法有效抑制血小板聚集。光透射聚集测定法(LTA)是血小板功能检测的金标准。在这项初步研究中,我们使用LTA在体外对动脉粥样硬化患者的ASA治疗进行个性化调整。招募了正在服用81毫克ASA的患者,他们前往圣迈克尔医院的门诊诊所(n = 64),有动脉粥样硬化疾病的证据,定义为有临床症状和诊断结果表明有症状性外周动脉疾病(PAD),踝臂指数(ABI)<0.9(n = 52),或有无症状性颈动脉狭窄(CAS)的诊断特征,经双功超声检查颈内动脉狭窄>50%(n = 12)。通过基于测量主要尿ASA代谢物水杨尿酸的多段注射-毛细管电泳-质谱法评估ASA依从性。使用花生四烯酸的LTA来检测ASA敏感性。在体外研究了162毫克和325毫克递增的ASA剂量以进行ASA剂量个性化。在招募的64名动脉粥样硬化患者中,8名患者(13%)未依从ASA治疗。在依从ASA治疗的患者(n = 56)中,9名患者(14%)对其81毫克ASA剂量不敏感。对81毫克ASA不敏感的患者递增ASA剂量进行个性化ASA治疗表明,6名患者对相当于162毫克ASA的剂量变得敏感,3名患者对相当于325毫克ASA的剂量变得敏感。我们能够在测试后1小时内通过递增ASA剂量在体外对所有ASA不敏感患者进行ASA剂量个性化调整。