Vergelijking tussen factor VIII gemeten met een activiteitsassay en met massaspectrometrie bij patienten met hemofilie a

Comparison between coagulation factor VIII quantified with one-stage activity assay and mass spectrometry in haemophilia A patients Background Haemophilia A is a hereditary bleeding disorder caused by a factor VIII (FVIil) deficiency. As biomark-er, FVIII activity is used to classify disease severity and to monitor treatment The one-stage clotting assay (OSA) is used to measure FVIII activity but OSA's limitations may result in reclassification of disease severity or suboptimal monitoring of treatment. Measurement of FVIII plasma concentration with LC-MS/MS might overcome these challenges. Objective To investigate the association between FVIII activity and concentration as well as determinants for discrepancies. Design and methods In this cross-sectional study, all haemophilia A patients receiving standard of care were eligible for inclusion. Within the activity categories of < 1%, 1-5%, > 5-40%, > 40-150%, and > 150-600% we randomly selected 15 to 20 plasma samples, and compared FVIII concentration (LC-MS/MS) to FVIII activity (OSA) with linear regression and Bland-Altman analysis. Potential determinants were analysed with linear regression. Results 87 samples were included. Bland-Altman analysis demonstrated an overall mean difference of-1% with a standard deviation (SD) of 64% between the two methods. Discrepancies were associated with the presence of anti-FVIII antibodies (133%, 95% confidence interval [95%CIJ = 81-185, n = 5) and exogenous FVIII products (-37%, 95%CI =-65-9, n = 58), e.g. plasma-derived and B-domain modified FVIII. Conclusion Despite almost no discrepancy overall, the variability between FVIII activity and FVIII concentration was large. Anti-FVIII antibodies or use of exogenous FVIII products might result in differences of potential clinical impact. More research is needed to determine the value of FVIII concentration in addition to activity.