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

Anne Fleur Zwagemaker, Fabienne R. Kloosterman, DYNAMO study group, Samantha C. Gouw, Sara Boyce, Paul Brons, Marjon H. Cnossen, Peter W. Collins, Jeroen Eikenboom, Charles Hay, Rutger C.C. Hengeveld, Shannon Jackson, Caroline A.M. Klopper-Tol, Marieke J.H.A. Kruip, Britta Laros van Gorkom, Christoph Male, Laurens Nieuwenhuizen, Susan Shapiro, Karin Fijnvandraat, Michiel Coppens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)850-861
Number of pages12
JournalJournal of Thrombosis and Haemostasis
Volume21
Issue number4
DOIs
Publication statusPublished - Apr 2023

Bibliographical note

Funding Information:
This work was funded by a grant from Novo Nordisk and supported by the Parelsnoer clinical biobank Hemophilia at the Health-RI (funded by the Ministry of Health , Welfare and Sport ). The funding sponsor had no role in the design and conduct of the study; data collection, management, analysis, and interpretation; and preparation, review, and approval of the manuscript. The authors thank Bianca Bakker, Debby Jongelings, and Caroline Klopper-Tol (coagulation laboratory, Amsterdam UMC) for their support at the laboratory and for performing the assays. In addition, the authors thank all local research staff for their help in setting up and conducting the study.

Funding Information:
Funding information This work was funded by a grant from Novo Nordisk and supported by the Parelsnoer clinical biobank Hemophilia at the Health-RI (funded by the Ministry of Health , Welfare and Sport ).

Publisher Copyright:
© 2022

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