Background: Thrombin generation (TG) is frequently measured in haemophilia patients to evaluate their baseline TG level, to monitor their response to therapy and to follow up patients in time. TG is also being used to compare efficacy and potency of potentially new treatment drugs. Many research groups use plasma from healthy controls spiked in vitro with an antibody (Ab) in order to mimic haemophilia plasma.

Aims: Our goal was to evaluate whether these in vitro mimicked samples have the same TG kinetics as haemophilia A samples and therefor are suitable for research purposes.

Methods: The Calibrated Automated Thrombogram was used to measure TG in plasma samples from healthy controls and haemophilia patients. Samples were spiked in vitro with recombinant FVIII (Kogenate, Bayer) and/or FVIII-Ab (PAHFVIII-S, HaemTech). Haemophilia A plasma was spiked with a buffer or with 100% FVIII and 15 µg/ml FVIII-Ab (to mimic haemophilia A again in the presence of the Ab). Plasma from healthy controls was spiked with 6 and 15 µg/ml FVIII-Ab. FVIII was measured using the STA R of Stago (France).

Results: When TG was measured in haemophilia A samples with and without FVIII-Ab, no differences could be observed between both plasma samples. A doses-response of FVIII could be observed for peak height, ETP, time-to-peak and velocity index, but not for lagtime, that seemed to be independent of the FVIII level. The FVIII doses-response in healthy controls with 6 and 15 µg/ml were parallel to each other, indicating that the differences between the two curves was dependent of the remaining FVIII level (94%, 34% and >4% for the samples with 0, 6 and 15 µg/ml FVIII-Ab, respectively).

Conclusions: No substantial differences were observed in TG kinetics, indicating that in vitro induced haemophilia samples can be used to determine the response to FVIII treatment in haemophilia A.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/prediction-of-the-response-to-fviii-treatment-in-haemophilia-a/