Accuracy of Factor VIII Assays for Measuring Damoctocog Alfa Pegol: A Comparative Analysis

Abstract

Introduction

Accurate monitoring of treatment with modified factor VIII products remains challenging, due to known variability in assay performance across different laboratory methods and reagents. For the extended half-life product Damoctocog alfa pegol discrepancies have been reported.

Aims

This multicentre field study was designed to evaluate the analytical accuracy of Damoctocog alfa pegol using various methods for one-stage clotting and chromogenic assays.

Methods

The study was conducted under conditions closely mimicking routine laboratory settings. Five plasma samples were spiked with varying concentrations of Damoctocog alfa pegol (0.05 to 1.3 IU/ml) and distributed to 118 participating laboratories. FVIII activity of the samples was analysed using 12 one-stage and 7 chromogenic methods. Accuracy results were evaluated per specific reagent with a maximal acceptable mean bias of 20% from the target. Interlaboratory variation was established for reagents with ≥3 participants.

Results

The reliability of factor VIII measurements differ between the tested reagents. Usage of SynthasIL and Pathromtin (one stage) and Biophen (chromogenic) is in most cases reliable, although inter-lab variation contributes to inaccuracy. The reagents STA PTT A and Triniclot (one stage), as well as Siemens (chromogenic) (strongly) underestimate FVIII activity and are therefore unsuitable for accurate measurement of Damoctocog alfa pegol.

Conclusion

We have evaluated accuracy results for 19 Factor VIII assays in order to provide evidence-based guidance for clinical laboratories in selecting appropriate assay methodologies for reliable quantification of the activity of Damoctocog alfa pegol. Assay performance should be locally validated as large interlaboratory variation is observed.