Assessment of Commutability in Factor VIII Activity Testing Using Fresh Human Plasma Samples

For the diagnosis and therapeutic monitoring of bleeding disorders as well as for thrombotic risk assessment, reliable measurement of factor VIII (FVIII) coagulant activity is required. The complex FVIII structure and limited stability pose major challenges in hemostaseological diagnostics concerning the preanalytical handling and the availability of commutable control and calibrator materials. The aim of this study was to assess the commutability of frozen and lyophilized patient plasma and routinely used external quality assessment materials (EQAMs) for FVIII activity measurement.FVIII activity was measured in 97 native plasma samples covering a broad activity range using clotting tests and chromogenic assays from two manufacturers. Corresponding frozen and lyophilized aliquots as well as four commercially available lyophilized control materials from three manufacturers were analyzed the same way. Commutability was assessed by comparing the mean natural logarithmic differences of candidate materials from those of native plasma using Bland-Altman plots. A commutability criterion was defined with respect to the intended use of the materials as EQAMs, based on the mean ± 2 standard deviations derived from the distribution of natural logarithmic differences in native plasma samples.Native plasma measurements showed good agreement across the four methods. Method-specific effects on FVIII activity measurement were minor after freezing, but more pronounced after lyophilization. Nevertheless, mean differences observed for frozen and lyophilized plasma remained within the predefined commutability criterion. All investigated EQAMs were deemed commutable for their intended use in external quality assessment. All in all, commutability studies for FVIII activity measurement are feasible but resource-intensive.