Little discrepancy between one-stage and chromogenic factor VIII (FVIII)/IX assays in a large international cohort of persons with nonsevere hemophilia A and B.

BACKGROUND

Accurate measurements of coagulation factor activity form an essential part of hemophilia management and are performed by the one-stage or chromogenic assay. Current literature suggests that approximately one-third of persons with nonsevere hemophilia A exhibit assay discrepancy, albeit with a high variability between studies. Such data are scarce in nonsevere hemophilia B.

OBJECTIVES

To investigate the extent of factor VIII/IX one-stage and chromogenic assay discrepancy in moderate and mild hemophilia A and B.

METHODS

Persons with previously diagnosed nonsevere hemophilia A and B with a factor level of 2 to 35 IU/dL were included from the international DYNAMO cohort study. Central measurements of the factor VIII and IX activity levels were performed by the one-stage and chromogenic assay. Relative and absolute discrepancy definitions were used, with the International Society on Thrombosis and Haemostasis-Scientific and Standardization Committee proposed ratio of >2.0 or <0.5 being the primary outcome. Discrepancy was also evaluated in a subgroup of 13 persons with mutations previously associated with discrepancy (≥3 cases reported in literature).

RESULTS

A total of 220 persons were included, of whom 3 (1%) showed assay discrepancy: 2/175 hemophilia A and 1/45 hemophilia B. Six persons (3%) exhibited an absolute difference >10 IU/dL between the assay results. In addition, with more lenient definitions, over 90% of participants (n = 197) had no discrepant results. Only 1 out of 13 persons with a mutation previously associated with discrepancy had significant assay discrepancy.

CONCLUSION

Little assay discrepancy was observed despite the presence of mutations previously associated with discrepancy, suggesting that the presence and magnitude of assay discrepancy are largely determined by laboratory variables.

Informations de copyright

Copyright © 2022. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest This work was supported by a grant from Novo Nordisk. S.C.G. has received an unrestricted research grant from Sobi. S.B. received research support from Sangamo Therapeutics and honoraria from CSL Behring. M.H.C. has received investigator-initiated research and travel grants as well as speaker fees over the years from the Netherlands Organisation for Scientific Research (NWO), the Netherlands Organization for Health Research and Development (ZonMw), the Dutch “Innovatiefonds Zorgverzekeraars”, Baxter/Baxalta/Shire/Takeda, Pfizer, Bayer Schering Pharma, CSL Behring, Sobi Biogen, Novo Nordisk, Novartis, and Nordic Pharma, and has served as a steering board member for Roche, Bayer, and Novartis. All grants, awards, and fees go to the Erasmus MC. P.W.C. had received research support from CSL Behring, and consultancy fees from CSL Behring, Novo Nordisk, Sobi, and Roche. J.E. received research support from CSL Behring and he has been a teacher on educational activities of Roche. S.J. has received financial support for research from Sanofi Genzyme and honoraria from Bayer, Takeda, Thrombosis Canada, Roche, Octapharma, and Hemalytic. The institution of M.J.H.A.K. has received unrestricted research grants from Sobi, and her institution received speakers’ fees from Sobi, Roche, and BMS. C.M. was a consultant or speaker for Bayer, Biotest, CSL Behring, Grifols, Novo Nordisk, Roche, and Takeda. He has received travel support from Bayer, Biotest, CSL Behring, and Novo Nordisk; his institution has received research support from Bayer, Takeda, Biotest, CSL Behring, Novo Nordisk, Roche, and Sobi. S.S. has received conference support, educational speaker fees, and/or advisory board fees from Pfizer, Bayer, Shire, Takeda, Sobi, Roche, and CSL Behring. K.F.’s institution has received unrestricted research grants from Sobi, Pfizer, CSL Behring, and Novo Nordisk, and also consultancy fees from Grifols, Takeda, Novo Nordisk, and Roche. M.C. reports research funding from Bayer, CSL Behring, Daiichi Saknyo, Novo Nordisk, Portola/Alexion, Roche, Sanquin Blood Supply, and UniQure and consultancy or lecturing fees from Bayer, CSL Behring, Novo Nordisk, Pfizer, and Sobi. A.Z., F.R.K., P.B., C.H., R.C.C.H., C.A.M.K.T., B.L.G., and L.N. have no potential conflicts of interest.