■评估血小板功能是诊断出血性疾病和评估抗血小板药物疗效的关键。然而,在解释血小板反应性的测量时,有一种流行的“一刀切”的方法,任意截止值通常来自健康的志愿者反应。
■我们的目的是比较常用的血小板反应性测定法。
■从弗雷明汉心脏研究中获得的血液和富含血小板的血浆(N=3429)使用5种血小板测定法中的一系列激动剂进行测定:光透射聚集测定法,优化的聚集测定法,多平板阻抗聚合法(罗氏诊断),总血栓形成分析系统,和流式细胞术。使用线性混合效应模型,我们确定了分析前和技术因素对血小板反应性特征的调节作用.
■在所有测定中都看到了血小板性状的强测定内相关性,特别是多层速度(r=0.740;瑞斯托霉素与花生四烯酸)。相比之下,仅观察到中等的测定间相关性(r=0.375;二磷酸腺苷OptimulEmax与光透射聚集法曲线下大面积)。不出所料,抗血小板药物强烈减少血小板反应,阿司匹林主要针对花生四烯酸诱导的聚集,并解释了实质性方差(β=-1.735;P=4.59×10-780;方差比例=46.2%)和P2Y12拮抗剂阻断二磷酸腺苷反应(β=-1.612;P=6.75×10-27;方差比例=2.1%)。值得注意的是,女性和年龄较大与血小板反应性增强相关.空腹状态和与标准静脉穿刺实践的偏差并未显着改变血小板反应性。最后,激动剂批次,采血师,和测定技术人员(对于需要额外样品操作的测定更是如此)对测量的血小板反应性具有中等至较大的影响。
■在测定之间推断结果时,必须谨慎行事,标准范围的使用必须至少是药物特异性和性别特异性的。在设计实验和解释血小板反应性测量时,研究人员还应考虑分析前和技术变量。
UNASSIGNED: Assessment of platelet function is key in diagnosing bleeding disorders and evaluating antiplatelet drug efficacy. However, there is a prevailing \"one-size-fits-all\" approach in the interpretation of measures of platelet reactivity, with arbitrary cutoffs often derived from healthy volunteer responses.
UNASSIGNED: Our aim was to compare well-used platelet reactivity assays.
UNASSIGNED: Blood and platelet-rich plasma obtained from the Framingham Heart Study (N = 3429) were assayed using a range of agonists in 5 platelet assays: light transmission aggregometry, Optimul aggregometry, Multiplate impedance aggregometry (Roche Diagnostics), Total Thrombus-Formation Analysis System, and flow cytometry. Using linear mixed-effect models, we determined the contribution of preanalytical and technical factors that modulated platelet reactivity traits.
UNASSIGNED: A strong intra-assay correlation of platelet traits was seen in all assays, particularly Multiplate velocity (r = 0.740; ristocetin vs arachidonic acid). In contrast, only moderate interassay correlations were observed (r = 0.375; adenosine diphosphate Optimul Emax vs light transmission aggregometry large area under the curve). As expected, antiplatelet drugs strongly reduced platelet responses, with aspirin use primarily targeting arachidonic acid-induced aggregation, and explained substantial variance (β = -1.735; P = 4.59 × 10-780; variance proportion = 46.2%) and P2Y12 antagonists blocking adenosine diphosphate responses (β = -1.612; P = 6.75 × 10-27; variance proportion = 2.1%). Notably, female sex and older age were associated with enhanced platelet reactivity. Fasting status and deviations from standard venipuncture practices did not alter platelet reactivity significantly. Finally, the agonist batch, phlebotomist, and assay technician (more so for assays that require additional sample manipulation) had a moderate to large effect on measured platelet reactivity.
UNASSIGNED: Caution must be exercised when extrapolating findings between assays, and the use of standard ranges must be medication-specific and sex-specific at a minimum. Researchers should also consider preanalytical and technical variables when designing experiments and interpreting platelet reactivity measures.