一种用于测量聚乙二醇化重组凝血因子VIII活性的产品特定参考标准的影响：瑞士多中心实地研究。

Impact of a product-specific reference standard for the measurement of a PEGylated rFVIII activity: the Swiss Multicentre Field Study.

作者信息

Bulla O, Poncet A, Alberio L, Asmis L M, Gähler A, Graf L, Nagler M, Studt J-D, Tsakiris D A, Fontana P

机构信息

Division of Angiology and Haemostasis and Laboratory of Haemostasis, Geneva University Hospitals, Geneva, Switzerland.

CRC and Division of Clinical Epidemiology, Department of Health and Community Medicine, University of Geneva and University Hospitals of Geneva, Geneva, Switzerland.

出版信息

Haemophilia. 2017 Jul;23(4):e335-e339. doi: 10.1111/hae.13250. Epub 2017 May 24.

DOI:10.1111/hae.13250

PMID:28544263

Abstract

INTRODUCTION

Measuring factor VIII (FVIII) activity can be challenging when it has been modified, such as when FVIII is pegylated to increase its circulating half-life. Use of a product-specific reference standard may help avoid this issue.

AIM

Evaluate the impact of using a product-specific reference standard for measuring the FVIII activity of BAX 855 - a pegylated FVIII - in eight of Switzerland's main laboratories.

METHODS

Factor VIII-deficient plasma, spiked with five different concentrations of BAX 855, plus a control FVIII sample, was sent to the participating laboratories. They measured FVIII activity by using either with a one-stage (OSA) or the chromogenic assay (CA) against their local or a product-specific reference standard.

RESULTS

When using a local reference standard, there was an overestimation of BAX 855 activity compared to the target concentrations, both with the OSA and CA. The use of a product-specific reference standard reduced this effect: mean recovery ranged from 127.7% to 213.5% using the OSA with local reference standards, compared to 110% to 183.8% with a product-specific reference standard, and from 146.3% to 182.4% using the CA with local reference standards compared to 72.7% to 103.7% with a product-specific reference standard.

CONCLUSION

In this in vitro study, the type of reference standard had a major impact on the measurement of BAX 855 activity. Evaluation was more accurate and precise when using a product-specific reference standard.

摘要

引言

当因子VIII（FVIII）被修饰时，比如将FVIII聚乙二醇化以延长其循环半衰期，测量其活性可能具有挑战性。使用产品特定的参考标准可能有助于避免这个问题。

目的

评估在瑞士八个主要实验室中，使用产品特定的参考标准来测量BAX 855（一种聚乙二醇化的FVIII）的FVIII活性的影响。

方法

将添加了五种不同浓度BAX 855的FVIII缺乏血浆，外加一个对照FVIII样本，送至参与研究的实验室。他们使用一步法（OSA）或发色底物法（CA），对照当地或产品特定的参考标准来测量FVIII活性。

结果

使用当地参考标准时，与目标浓度相比，无论是采用OSA还是CA，BAX 855活性均被高估。使用产品特定的参考标准可减少这种影响：使用OSA并对照当地参考标准时，平均回收率在127.7%至213.5%之间，而对照产品特定参考标准时为110%至183.8%；使用CA并对照当地参考标准时，平均回收率在146.3%至182.4%之间，而对照产品特定参考标准时为72.7%至103.7%。