Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
Norwegian Organization for Quality Improvement of Laboratory Examinations (Noklus), Haraldsplass Deaconess Hospital, Bergen, Norway.
Clin Chem. 2021 Sep 1;67(9):1259-1270. doi: 10.1093/clinchem/hvab100.
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.
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.
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.
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.
为了安全地使用生物学变异 (BV) 数据，数据必须是可靠的，并且与应用它们的人群相关。我们使用来自欧洲生物学变异研究 (EuBIVAS) 的样本，通过对极端观测值稳健的贝叶斯模型来确定凝血标志物的 BV，并使用得出的个体内 BV 估计值 [CVP(i)] 来评估 BV 估计值在临床实践中的适用性。
从欧洲的 6 个实验室的 92 名健康个体中抽取血浆样本，连续 10 周每周抽取 6 份，并对激活部分凝血活酶时间 (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 游离和因子 VIII (FVIII) 进行重复分析。应用具有样本和重复项学生 t 似然的贝叶斯模型，得出 CVP(i) 和预测的 95%可信度区间的 BV 估计值。
除了 D-二聚体，所有标志物的 CVP(i)在整个研究人群或亚组中均呈均匀分布。对于 APTT、PT、AT 和蛋白 S 游离，个体内估计值 (CVI) <5%；对于蛋白 C 和 FVIII，CVI <10%；对于纤维蛋白原，CVI <12%。对于 APTT、蛋白 C 和蛋白 S 游离，男性的估计值明显低于≤50 岁的女性。
对于大多数凝血标志物，男性和女性的共同 CVI 估计值是适用的，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。使用贝叶斯模型提供个体 CVP(i) 允许更好地解释和应用数据。
