Abstract

D-dimer is considered to be a reliable marker of both coagulation activation and fibrinolysis. However, data on biological variation (BV) of D-dimer is still limited, causing the use of empiric analytical performance specifications and lack of other implications related to BV. This study aimed to estimate the BV of plasma D-dimer employing a study design compliant with The Biological Variation Data Critical Appraisal Checklist. Blood samples were collected from a cohort of 25 healthy subjects (16 females, 9 males; age range, 19–61 years) from Turkey once weekly for 3 consecutive weeks. All plasma samples were analyzed in duplicate within a single run on Roche Cobas c501. The results were assessed for outliers, variance homogeneity, normal distribution, and trend, followed by nested ANOVA to determine BV and analytical variation estimates with confidence intervals (CIs). Gender stratified BV estimates were also calculated. Within-subject (CV_I) and between-subject (CV_G) BV estimates with 95% CIs were for D-dimer 21.2% (17.8-25.9) and 30.9% (21.3-46.2), respectively. No significant BV differences were observed between females and males. The index of individuality (II) and the reference change value (RCV) were calculated as 0.71 and 60.4%, respectively. Analytical performance specifications for desirable imprecision, bias, and total error were 10.6, 9.4, and 26.8%, respectively. This study provides well-characterized BV estimates for D-dimer, which may be helpful for setting objectively analytical performance specifications. Moreover, RCV should be preferred to decide whether a significant difference is present between serial D-dimer measurements from an individual.

摘要

D-二聚体被认为是凝血激活和纤溶的可靠标志物。然而，关于 D-二聚体的生物变异 (BV) 的数据仍然有限，导致使用经验分析性能规范并且缺乏与 BV 相关的其他含义。本研究旨在估计血浆 D-二聚体的 BV，采用符合生物变异数据关键评估清单的研究设计。从土耳其的 25 名健康受试者（16 名女性，9 名男性；年龄范围，19-61 岁）的队列中收集血液样本，每周一次，连续 3 周。在 Roche Cobas c501 上一次运行中对所有血浆样品进行一式两份分析。评估结果的异常值、方差同质性、正态分布和趋势，其次是嵌套方差分析以确定 BV 和具有置信区间 (CI) 的分析变异估计。还计算了性别分层的 BV 估计值。学科内（CV_I ) 和受试者间 (CV _G ) BV 估计值的 95% CI 分别为 D-二聚体 21.2% (17.8-25.9) 和 30.9% (21.3-46.2)。在女性和男性之间没有观察到显着的BV差异。个体指数（II）和参考变化值（RCV）分别计算为0.71和60.4%。理想的不精密度、偏差和总误差的分析性能指标分别为 10.6、9.4 和 26.8%。本研究为 D-二聚体提供了充分表征的 BV 估计值，这可能有助于设定客观的分析性能规范。此外，应该首选 RCV 来确定个体的连续 D-二聚体测量之间是否存在显着差异。