Background For biological variation (BV) data to be safely used, data must be reliable and relevant to the population in which they are applied. We used samples from the European Biological Variation Study (EuBIVAS) to determine BV of coagulation markers by a Bayesian model robust to extreme observations and used the derived within-participant BV estimates [CVP(i)] to assess the applicability of the BV estimates in clinical practice. Method Plasma samples were drawn from 92 healthy individuals for 10 consecutive weeks at 6 European laboratories and analyzed in duplicate for activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, D-dimer, antithrombin (AT), protein C, protein S free, and factor VIII (FVIII). A Bayesian model with Student t likelihoods for samples and replicates was applied to derive CVP(i) and predicted BV estimates with 95% credibility intervals. Results For all markers except D-dimer, CVP(i) were homogeneously distributed in the overall study population or in subgroups. Mean within-subject estimates (CVI) were <5% for APTT, PT, AT, and protein S free, <10% for protein C and FVIII, and <12% for fibrinogen. For APTT, protein C, and protein S free, estimates were significantly lower in men than in women ≤50 years. Conclusion For most coagulation markers, a common CVI estimate for men and women is applicable, whereas for APTT, protein C, and protein S free, sex-specific reference change values should be applied. The use of a Bayesian model to deliver individual CVP(i) allows for improved interpretation and application of the data.

中文翻译：

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欧洲生物变异研究 (EuBIVAS)：贝叶斯模型估计的凝血标志物的生物变异数据

背景 为了安全使用生物变异 (BV) 数据，数据必须可靠且与应用它们的人群相关。我们使用来自欧洲生物变异研究 (EuBIVAS) 的样本，通过对极端观察结果稳健的贝叶斯模型确定凝血标志物的 BV，并使用派生的参与者内 BV 估计值 [CVP(i)] 来评估 BV 估计值在临床实践。方法 在 6 个欧洲实验室连续 10 周从 92 名健康个体中抽取血浆样本，并重复分析活化部分促凝血酶原激酶时间 (APTT)、凝血酶原时间 (PT)、纤维蛋白原、D-二聚体、抗凝血酶 (AT)、蛋白 C、蛋白 S 和因子 VIII (FVIII)。应用具有样本和复制的学生 t 可能性的贝叶斯模型来推导 CVP(i) 并预测 BV 估计值，可信区间为 95%。结果 对于除 D-二聚体以外的所有标志物，CVP(i) 在整个研究人群或亚组中均匀分布。APTT、PT、AT 和无蛋白 S 的平均受试者内估计值 (CVI) ＜5%，蛋白 C 和 FVIII ＜10%，纤维蛋白原＜12%。对于 APTT、蛋白 C 和蛋白 S 游离，男性的估计值显着低于 ≤50 岁的女性。结论 对于大多数凝血标志物，适用于男性和女性的通用 CVI 估计值，而对于 APTT、蛋白 C 和蛋白 S 游离，应应用性别特异性参考变化值。