An international collaborative study to establish the WHO 3rd International Standard for Thrombin: Communication from the ISTH SSC subcommittee on factor XIII and fibrinogen. (2nd March 2021)

• Record Type: Journal Article
• Authors: Locke, Matthew; Longstaff, Colin; Rigsby, Peter
• Is Part Of: Journal of thrombosis and haemostasis. Volume 19:Number 3(2021)
• Page Start: 852
• Page End: 858
• Publication Date: 2021-03-02
• Subjects: clotting -- reference standards -- standardization -- thrombin; Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.15207
• Languages: English
• ISSNs: 1538-7933

Abstract

Abstract: The calibration of thrombin products relies on the World Health Organization (WHO) 2nd International Standard (IS) for Thrombin (01/580) which defines the international unit (IU) for thrombin potency. With stocks of the 2nd IS (01/580) running low, an international collaborative study was organized to calibrate a replacement. Twenty laboratories from 13 countries took part in the study and measured the potency of two candidate replacement standards (coded 01/578 and 19/188) relative to the 2nd IS. In total, 111 valid assays were returned, which were a combination of plasma/fibrinogen clotting assays and chromogenic assays. Variation between and within laboratories was low, with inter‐ and intra‐laboratory geometric coefficient of variation (GCV) generally <5% for all assay methods and substrates. For 01/578, potency estimates by clotting assays (101.1 IU/ampoule) were significantly lower than estimates by chromogenic assays (111.5 IU/ampoule). Mean potency estimates for 19/188 were 90.4 IU/ampoule by clotting assay and 88.1 IU/ampoule by chromogenic assay, which was not a statistically significant difference. The close ratio between clotting and chromogenic assay potency estimates for 19/188 suggests it has a higher α‐thrombin content than 01/578 and is equivalent to the current IS (01/580). Accelerated degradation studies predicted excellent long‐term stability profiles for preparations 01/580, 01/578, and 19/188. Based on the results of this study, the WHO Expert Committee on Biological Standardization established 19/188 as the 3rd IS for Thrombin with a potency of 90 IU/ampoule in August 2020.