Thrombin generation assay using factor XIa to measure factors VIII and IX and their glycoPEGylated derivatives is robust and sensitive

Journal of Thrombosis and Haemostasis : JTH
E K WatersPernille K Holm

Abstract

Conventional coagulation factor assays are associated with certain limitations, as they do not always reflect the clinical heterogeneity of bleeding in hemophilic patients or correctly reflect the individual patient response to treatment with bypassing agents or novel factor concentrates. The thrombin generation assay (TGA) is currently being assessed as a possible method for characterizing bleeding phenotypes in individuals with hemophilia. This study assessed the robustness and sensitivity of the TGA for measuring the activity of recombinant factor VIII (rFVIII), recombinant factor IX (rFIX) and their glycoPEGylated derivatives, N8-GP and N9-GP, in vitro. Factor-deficient plasma was spiked with 0.13-130 IU dL(-1) rFVIII or N8-GP (hemophilia A [HA] plasma), or rFIX or N9-GP (hemophilia B [HB] plasma). A calibrated automated thrombogram triggered with tissue factor (TF) or activated FXI (FXIa) was used to measure thrombin generation over time. Endogenous thrombin potential, peak thrombin, velocity index, lag time and time to peak thrombin were analyzed. FXIa-triggered assays were not affected by glycoPEGylation and were sufficiently sensitive to differentiate between spiked samples mimicking severe and moderate HB and HA; TF-tr...Continue Reading

References

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Citations

Apr 3, 2016·Haemophilia : the Official Journal of the World Federation of Hemophilia·N K JhaM V Ovanesov
Jun 7, 2016·British Journal of Haematology·Keiji Nogami
Aug 17, 2018·Haemophilia : the Official Journal of the World Federation of Hemophilia·Donald F BrophyMirella Ezban
Jan 22, 2019·Haemophilia : the Official Journal of the World Federation of Hemophilia·Mirella EzbanEgon Persson
Feb 23, 2018·British Journal of Haematology·Michael J R DesboroughNicola Curry
Dec 7, 2019·Haemophilia : the Official Journal of the World Federation of Hemophilia·Mirella EzbanMarianne Kjalke
Jan 19, 2019·Research and Practice in Thrombosis and Haemostasis·Egon PerssonMartin Hansen
Mar 20, 2019·Journal of Thrombosis and Haemostasis : JTH·Nina C LeksaJoe Salas
Feb 29, 2020·Research and Practice in Thrombosis and Haemostasis·Saman AghighiPratima Chowdary
Dec 17, 2019·Biomacromolecules·Abdullah Al NahainVito Ferro

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