An integrated framework for universal coagulation test reference intervals: Cross-platform validation of eleven indirect algorithms and age-specific hierarchical optimization

IF 3.2 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta Pub Date : 2025-06-09 DOI:10.1016/j.cca.2025.120422

Yunfeng Wu , Tingting Huang , Huixian Huang, Fan Yu, Jiao Liu, Xi Tang, Lei Chen, Yiwen Zhou, Haihong He

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引用次数: 0

Abstract

Background

The conventional direct method for establishing coagulation reference intervals (RIs) faces challenges, including difficulties in recruiting healthy populations, non-Gaussian distributions, and complex age-related effects. Indirect methods utilizing real-world data (RWD) are limited by a lack of consensus on algorithm selection and insufficient cross-platform validation.

Objective

To develop a multi-algorithm collaborative framework for systematically evaluating the performance of 11 outlier detection algorithms, thereby optimizing coagulation RIs for the Chinese population and validating their cross-platform applicability.

Methods

We retrospectively analysed 630,946 coagulation test records from Shenzhen Hospital of Southern Medical University. Outlier removal was performed using eleven algorithms. Algorithm stability and sex/age effects were quantified via reference change value (RCV) and variance component models. Validation was conducted across Mindray CX-9000 and Stago STA R Max platforms.

Results

Among the 11 algorithms, Z-Score and Tukey demonstrated optimal performance for 8 coagulation parameters, yielding RIs with minimal deviation from manufacturer standards. Sex-based analysis revealed minimal differences (Standard deviation ratio (SDR) < 0.40, Standardized effect size (Cohen’s d) <0.50), eliminating the need for sex stratification. Age stratification was required for D-Dimer (≥60 years subgroup: SDR = 0.62, Cohen’s d = 0.54). Cross-platform consistency confirmed algorithm generalizability.

Conclusions

This RCV-driven multi-algorithm framework establishes the Z-Score and Tukey methods as optimal for coagulation RIs derivation, advocates age-specific D-Dimer RIs, and deems sex stratification unnecessary. This scalable approach enhances standardization in coagulation testing.

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通用凝血测试参考区间的集成框架：11种间接算法的跨平台验证和特定年龄的分层优化

传统的凝血参考区间（RIs）直接测定方法面临诸多挑战，包括难以招募健康人群、非高斯分布以及复杂的年龄相关效应。利用真实世界数据（RWD）的间接方法受到算法选择缺乏共识和跨平台验证不足的限制。目的开发一个多算法协作框架，系统评估11种离群值检测算法的性能，从而优化中国人群的凝血RIs并验证其跨平台适用性。方法回顾性分析南方医科大学深圳医院630946例凝血试验记录。使用11种算法进行异常值去除。通过参考变化值（RCV）和方差成分模型量化算法稳定性和性别/年龄效应。验证在迈瑞CX-9000和Stago STA R Max平台上进行。结果在11种算法中，Z-Score和Tukey在8个凝血参数上表现最佳，产生的RIs与制造商标准偏差最小。基于性别的分析显示差异很小(标准偏差比(SDR <；0.40，标准化效应大小（Cohen 's d） <0.50)，消除了性别分层的需要。d -二聚体需要年龄分层（≥60岁亚组：SDR = 0.62, Cohen 's d = 0.54）。跨平台一致性证实了算法的通用性。结论该rcv驱动的多算法框架确立了Z-Score和Tukey方法是凝血RIs衍生的最佳方法，提倡年龄特异性d -二聚体RIs，认为性别分层是不必要的。这种可扩展的方法增强了凝血测试的标准化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinica Chimica Acta 医学-医学实验技术

CiteScore

10.10

自引率

2.00%

发文量

1268

审稿时长

23 days

期刊介绍： The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.