Colorado Coagulation, Laboratory Corporation of America® Holdings, Englewood, Colorado.
Hematology Department, University Children's Hospital, Zürich, Switzerland.
Haemophilia. 2019 Jul;25(4):708-717. doi: 10.1111/hae.13763. Epub 2019 May 20.
Accurate determination of coagulation factor VIII activity (FVIII:C) is essential for effective and safe FVIII replacement therapy.
C can be measured by one-stage and chromogenic substrate assays (OSAs and CSAs, respectively); however, there is significant interlaboratory and interassay variability.
This international comparative field study characterized the behaviour of OSAs and CSAs used in routine laboratory practice to measure the activity of Nuwiq (human-cl rhFVIII, simoctocog alfa), a fourth-generation recombinant human FVIII produced in a human cell line.
FVIII-deficient plasma was spiked with Nuwiq or Advate at 1, 5, 30 and 100 international units (IU)/dL. Participating laboratories analysed the samples using their routine procedures and equipment. Accuracy, inter- and intralaboratory variation, CSA:OSA ratio and the impact of different OSA and CSA reagents were assessed.
Forty-nine laboratories from 9 countries provided results. Mean absolute FVIII:C was comparable for both products at all concentrations with both OSA and CSA, with interproduct ratios (Nuwiq :Advate ) of 1.02-1.13. Mean recoveries ranged from 97% to 191% for Nuwiq , and from 93% to 172% for Advate , with higher recoveries at lower concentrations. Subgroup analyses by OSA and CSA reagents showed minor variations depending on reagents, but no marked differences between the two products. CSA:OSA ratios based on overall means ranged from 0.99 to 1.17 for Nuwiq and from 1.01 to 1.17 for Advate .
Both OSAs and CSAs are suitable for the measurement of FVIII:C of Nuwiq in routine laboratory practice, without the need for a product-specific reference standard.
准确测定凝血因子 VIII 活性（FVIII：C）对于 FVIII 替代治疗的有效和安全至关重要。
C 可以通过一步法和显色底物测定法（OSA 和 CSA，分别）进行测量；然而，存在显著的实验室间和测定内变异性。
本国际比较现场研究描述了在常规实验室实践中用于测量 Nuwiq（人源 cl rhFVIII，simoctocog alfa）活性的 OSA 和 CSA 的行为，Nuwiq 是一种在人细胞系中产生的第四代重组人 FVIII。
用 Nuwiq 或 Advate 将 FVIII 缺乏的血浆分别在 1、5、30 和 100 国际单位（IU）/dL 水平下进行了加标。参与实验室使用其常规程序和设备对样品进行了分析。评估了准确性、室内和室间变异性、CSA：OSA 比值以及不同 OSA 和 CSA 试剂的影响。
来自 9 个国家的 49 个实验室提供了结果。使用两种 OSA 和 CSA 时，两种产品在所有浓度下的平均绝对 FVIII：C 均具有可比性，两种产品之间的产品比值（Nuwiq：Advate）为 1.02-1.13。Nuwiq 的回收率范围为 97%-191%，Advate 的回收率范围为 93%-172%，回收率随着浓度的降低而升高。根据 OSA 和 CSA 试剂进行的亚组分析显示，根据试剂略有差异，但两种产品之间没有明显差异。基于总体平均值的 CSA：OSA 比值，Nuwiq 的范围为 0.99-1.17，Advate 的范围为 1.01-1.17。
在常规实验室实践中，两种 OSA 和 CSA 均适合测量 Nuwiq 的 FVIII：C，无需使用特定于产品的参考标准。
