Favaloro Emmanuel J, McVicker Wendy, Zhang Yifang, Hamdam Sayed, Huynh Michelle, Peris Padmini, O'Neal Matthew, Hocker Naomi
Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead.
Clin Lab Sci. 2012 Winter;25(1):13-25.
The Prothrombin Time (PT) assay is clinically the most often requested coagulation test, as used primarily for monitoring of Vitamin K antagonist therapy where results are typically expressed as an International Normalized Ratio (INR). The INR reflects the patient's PT adjusted for the specific test reagent and instrument combination used by applying two correction factors, namely the International Sensitivity Index (ISI) and the Mean Normal Prothrombin Time (MNPT), according to the formula: INR = (patient PT/MNPT)ISI. When the manufacturer provides an ISI, laboratories are encumbered to check or locally validate the assigned value. Where a manufacturer does not provide an ISI, the laboratory needs to define its own (local ISI) value. The MNPT typically has to be locally defined, based on the population being tested. The main current CLSI recommendation for defining ISI values comprises use of commercial reference ('certified') plasma calibration sets, but FDA cleared material is limited, and different results may arise using different products. The MNPT can be defined using a WHO/CLSI recommended procedure requiring 20 normal individuals or with some calibration sets. Overall, there is limited data to validate the performance of these processes in laboratory practice, and ongoing evidence from external quality assurance (proficiency testing) programs indicates continued failure in INR harmonization, suggesting that ISI and MNPT values used by laboratories (and presumably assessed using current recommended processes) continue to be inaccurate.
To assess some novel approaches to the laboratory estimation and/or validation of ISI and MNPT values for use in the INR calculation, and including the process of 'transference', normally used to assess the comparability of analytical systems or to transfer reference intervals between comparable systems.
We have successfully adapted these comparative procedures, including 'transference', to permit ongoing estimation and/or validation of ISI and MNPT values for use in INR calculations for a range of instrumentation, which has led to improved harmonization of INR values obtained in our pathology network. These processes do not require the use of any normal individual plasmas or calibrator sets and greatly simplifies the INR process. Evidence for validation of the processes used is provided by ongoing satisfactory performance in external quality assurance (proficiency testing).
凝血酶原时间（PT）检测是临床上最常要求进行的凝血试验，主要用于监测维生素K拮抗剂治疗，其结果通常以国际标准化比值（INR）表示。INR反映了根据公式INR =（患者PT/平均正常凝血酶原时间[MNPT]）国际敏感指数（ISI），针对所使用的特定测试试剂和仪器组合对患者PT进行校正后的结果。当制造商提供ISI时，实验室有责任检查或在本地验证所指定的值。如果制造商未提供ISI，实验室则需要自行定义其（本地ISI）值。MNPT通常必须根据所检测的人群在本地进行定义。当前CLSI关于定义ISI值的主要建议包括使用商业参考（“认证”）血浆校准套件，但FDA批准的材料有限，并且使用不同产品可能会产生不同结果。MNPT可以使用世界卫生组织/CLSI推荐的程序来定义，该程序需要20名正常个体或一些校准套件。总体而言，在实验室实践中验证这些过程性能的数据有限，并且来自外部质量保证（能力验证）计划的现有证据表明INR标准化仍持续失败，这表明实验室使用的ISI和MNPT值（大概是使用当前推荐的过程进行评估的）仍然不准确。
评估一些用于实验室估计和/或验证用于INR计算的ISI和MNPT值以及包括“转移”过程的新方法，“转移”过程通常用于评估分析系统的可比性或在可比系统之间转移参考区间。
我们已成功采用这些比较程序，包括“转移”，以允许对一系列仪器进行用于INR计算的ISI和MNPT值的持续估计和/或验证，这已导致我们病理网络中获得的INR值的标准化得到改善。这些过程不需要使用任何正常个体血浆或校准套件，并且极大地简化了INR过程。外部质量保证（能力验证）中持续令人满意的表现为所使用的过程提供了验证证据。
