Pre-analytical storage and reagent-dependent sensitivity as sources of variability in prothrombin time and activated partial thromboplastin time measurements

IF 3.4 3区医学 Q1 HEMATOLOGY

Thrombosis research Pub Date : 2026-07-01 Epub Date: 2026-06-28 DOI:10.1016/j.thromres.2026.109771

A.D. van Dam, M.M. Bioch, E.H. Jeninga, J.B. de Kok, S.R. Rijpma, M.H.M. Thelen, Y.M.C. Henskens, R.G.M. van Oerle, A.K. Stroobants, Coagulation Section of the Dutch Foundation for Quality Assessment in Medical Laboratory Diagnostics (SKML)

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引用次数: 0

Abstract

Background

Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are widely used coagulation assays whose results can vary due to pre-analytical and analytical factors. Understanding these sources of variability is essential for reliable laboratory practice and external quality assessment (EQA).

Objectives

This study evaluates the impact of pre-analytical storage and method-dependent sensitivity on PT and aPTT measurements and provides guidance for EQA programmes and clinical interpretation.

Methods

Plasma samples from 42 healthy volunteers were analysed within 4 h of collection or after storage at −20 °C, −80 °C, or snap-frozen in liquid nitrogen (LN₂) and subsequent storage at −80 °C. Additionally, pooled plasma was spiked with direct oral anticoagulants, heparins, and lupus anticoagulant antibodies to assess reagent-specific sensitivity. PT and aPTT were measured on multiple routine platforms using commonly used reagents from 4 different manufacturers.

Results

Storage at −80 °C or LN₂ preserved PT and aPTT values, whereas storage at −20 °C caused variable prolongation. In healthy volunteers, PT and aPTT showed marked inter-method variability. Sensitivity to anticoagulants and lupus anticoagulant also differed considerably between reagents, with the largest variation observed for edoxaban. This study provides an overview of inter-method variability, which may affect clinical decision-making and inter-laboratory comparability.

Conclusions

PT and aPTT are screening tests whose accurate interpretation depends on optimal sample handling and awareness of reagent- and method-specific sensitivities. These differences can affect clinical decision-making in anticoagulated patients. EQA programmes could increase their value by using frozen plasma, including clinically relevant anticoagulants, and implementing case-based scenarios rather than reporting only clotting times.

查看原文本刊更多论文

在凝血酶原时间和活化的部分凝血活酶时间测量中，分析前储存和试剂依赖敏感性作为可变性的来源。

背景：凝血酶原时间（PT）和活化部分凝血活素时间（aPTT）是广泛使用的凝血试验，其结果可能因分析前和分析因素而有所不同。了解这些可变性的来源对于可靠的实验室实践和外部质量评估（EQA）至关重要。目的：本研究评估分析前储存和方法依赖敏感性对PT和aPTT测量的影响，并为EQA方案和临床解释提供指导。方法：42名健康志愿者的血浆样本在采集后4小时内、-20°C、-80°C或液氮快速冷冻后-80°C保存后进行分析。此外，汇集血浆中加入直接口服抗凝剂、肝素和狼疮抗凝抗体，以评估试剂特异性敏感性。PT和aPTT在多个常规平台上使用4个不同厂家的常用试剂进行检测。结果：-80°C或LN 2保存PT和aPTT值，而-20°C保存导致不同的延长。在健康志愿者中，PT和aPTT表现出明显的方法间差异。对抗凝血剂和狼疮抗凝血剂的敏感性在不同试剂之间也有很大差异，以依多沙班的差异最大。本研究概述了可能影响临床决策和实验室间可比性的方法间可变性。结论：PT和aPTT是筛选试验，其准确的解释取决于最佳的样品处理和试剂和方法特异性敏感性的意识。这些差异会影响抗凝患者的临床决策。EQA项目可以通过使用冷冻血浆（包括临床相关的抗凝剂）和实施基于病例的方案而不是仅报告凝血时间来增加其价值。

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

Thrombosis research 医学-外周血管病

CiteScore

14.60

自引率

4.00%

发文量

364

审稿时长

31 days

期刊介绍： Thrombosis Research is an international journal dedicated to the swift dissemination of new information on thrombosis, hemostasis, and vascular biology, aimed at advancing both science and clinical care. The journal publishes peer-reviewed original research, reviews, editorials, opinions, and critiques, covering both basic and clinical studies. Priority is given to research that promises novel approaches in the diagnosis, therapy, prognosis, and prevention of thrombotic and hemorrhagic diseases.