title: Establishment of the World Health Organization 2ndInternational Standard for Factor XI, Plasma, Human.
abstract: The 1stInternational Standard (IS) for blood coagulation factor XI (FXI), plasma, has been successfully used for potency labeling of FXI therapeutics and for diagnosis of FXI deficiency in patients. With stocks of the 1stIS near depletion, a replacement is required. In addition to the functional activity value, assignment of an antigen value to the 2ndIS would allow harmonization of antigen assay methods and differentiation of patients who have low functional activity but normal antigen FXI levels from patients who have both low functional and antigen FXI levels. The aims of this study were, therefore, to assign FXI functional activity to the 2ndIS for FXI, plasma, and to additionally assign a new analyte, FXI antigen, to the same International Standard. The candidate material was prepared from double-spun, virology negative, normal plasma, which was pooled and filled into siliconized glass ampoules and subsequently freeze-dried. Assignment of the functional activity (FXI:C) value in International Units (IUs) was performed by one-stage clotting assay by 29 laboratories, relative to the 1stIS. The overall geometric mean (GM) was 0.71 IU/amp with extremely low inter-laboratory variability (expressed as geometric coefficient of variation) of 1.8%. The antigen value assignment was performed by 11 laboratories and was calculated relative to normal plasma pools, as is customary with new coagulation factor analytes. The amount of antigen present in 1 ml of normal plasma was taken to be 1 U. The overall GM for the antigen assays was 0.78 IU/amp with an inter-laboratory variation of 10%. The candidate (National Institute for Biological Standards and Control code, 15/180) was established by the World Health Organization (WHO) Expert Committee on Biological Standardization in 2016 as the WHO 2ndIS for blood coagulation FXI, plasma, with a functional activity value (FXI:C) of 0.71 IU/amp and an antigen value (FXI:Ag) of 0.78 IU/amp.
authors.affiliation: Haemostasis Section, National Institute for Biological Standards and Control , Potters Bar, Hertfordshire , UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Wilmot
authors.affiliation: Biostatistics Group, National Institute for Biological Standards and Control , Potters Bar, Hertfordshire , UK.
authors.forename: Jason
authors.initials: J
authors.lastname: Hockley
authors.affiliation: Biostatistics Group, National Institute for Biological Standards and Control , Potters Bar, Hertfordshire , UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Rigsby
authors.affiliation: Haemostasis Section, National Institute for Biological Standards and Control , Potters Bar, Hertfordshire , UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Gray
keywords: International Standard for factor XI; factor XI antigen; factor XI functional activity; measurement of factor XI; multicentre study