Evaluating the thrombin generation profiles of four different rFVIII products in FVIII‐deficient plasma using FIXa and FXIa activation. Issue 5 (16th August 2018)

• Record Type: Journal Article
• Authors: Brophy, Donald F.; Martin, Erika J.; Ninivaggi, Marisa; Mohammed, Bassem M.; Barrett, John C.; Kuhn, Janice; Nolte, Melinda E.; Waters, Emily K.; Ezban, Mirella
• Is Part Of: Haemophilia. Volume 24:Issue 5(2018)
• Page Start: 815
• Page End: 822
• Publication Date: 2018-08-16
• Subjects: factor IXa -- factor VIII -- factor XIa -- haemophilia -- one‐stage assay -- thrombin generation assay; Hemophilia -- Periodicals; 616.1572005
• DOI: 10.1111/hae.13597
• Languages: English
• ISSNs: 1351-8216

Abstract

Abstract : Introduction: The thrombin generation assay (TGA) can be used to monitor factor replacement therapy in patients with haemophilia. The TGA assay is typically performed using tissue factor as the reaction activator; however, activating with FIXa or FXIa can enhance assay sensitivity when FVIII < 1%. Aims: To evaluate the sensitivity of the TGA when FIXa (5 nmol/L) and FXIa (0.22 nmol/L) are used to activate the assay in platelet‐poor plasma and to compare these data to the one‐stage and chromogenic assays. Methods: Plasma from 10 severe FVIII‐deficient subjects was supplemented with FVIII (0%, 0.1%, 0.4%, 1.2%, 4%, 11% and 33%), using either Novo Eight ®, Advate ®, Eloctate ®, turoctocog alfa pegol or a control standard. The one‐stage and chromogenic assays quantified the FVIII levels. The TGA assay was activated using either FIXa or FXIa. Results: Both FIXa‐ and FXIa‐activated TGA were sensitive across FVIII concentrations, with intra‐assay coefficient of variation (CV) < 10%. The FXIa‐activated assay had 25% CV at the lowest level of FVIII compared to 10% CV with FIXa activation. There were strong correlations between the FIXa‐ and FXIa‐activated TGA tests ( R 2 = 0.9912) and between the one‐stage and chromogenic assays ( R 2 = 0.9469). However, there were poor relationships between the TGA tests and one‐stage and chromogenic assays. Conclusions: Both FIXa‐ and FXIa activation results in similar TGA profiles across a FVIII range of 0.1%‐33%; however, FIXa activation was more robust at the lowest levels of FVIII compared with FXIa activation.