Abstract Number: PB1149
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Novel Biotherapeutics in Hemophilia
Background: The treatment of patients with inhibitors currently involves using bypassing agents (BPA). Recently, the novel agent, emicizumab, has demonstrated a significant reduction in the rate of bleeding compared to BPA.
Aims: What remains unclear is the degree to which emicizumab corrects the clotting defect, and the objective of this study was to address this question.
Methods: Patients with mild/moderate hemophilia (group 1) and severe hemophilia patients with inhibitors on emicizumab (group 2) participated in the study. Blood drawn from both groups were assayed for FVIII activity (group 1) and thrombin generation (both groups). First, linear regression was utilized to model the FVIII levels as a function of the endogenous thrombin potential (ETP) and peak thrombin. Then, we used the results of the emicizumab patients (group 2) with the calibration curve to calculate their predicted FVIII level. Association between patient weight and their predicted FVIII levels were evaluated by linear regression.
Results: Twenty five patients with moderate and mild hemophilia and 11 patients with severe hemophilia and inhibitors on emicizumab were enrolled. Figure-1 demonstrates the raw data and the regression line for the FVIII levels versus ETP for group 1 and the squares represent the predicted FVIII levels for patients on emicizumab based on their actual ETP. Figure 2 shows the relationship between the inhibitor patient’s weight and their predicted FVIII level.
Conclusions: All the patients on emicizumab had predicted FVIII levels above 10% with most having levels above 20%. The wide variability in the predicted FVIII level was tightly correlated to weight with the heaviest patients having the lowest FVIII predicted levels. It is unclear at this time why this may be the case, and further data will be collected to assess this relationship. Moving forward, understanding the correction of the clotting defect of non-replacement therapies is an important goal.
[Figure 1: Predicted FVIII for severe Hemophilia A patients on emicizumab]
[Figure -2: Relationship between pateints’ weight and predicted FVIII level]
To cite this abstract in AMA style:
Kizilocak H, Marquez-Casas E, Malvar J, Carmona R, Young G. Determining the Approximate Factor VIII Level Equivalency of Patients with Severe Hemophilia A on Emicizumab Using Global Hemostasis Assays [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/determining-the-approximate-factor-viii-level-equivalency-of-patients-with-severe-hemophilia-a-on-emicizumab-using-global-hemostasis-assays/. Accessed October 1, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/determining-the-approximate-factor-viii-level-equivalency-of-patients-with-severe-hemophilia-a-on-emicizumab-using-global-hemostasis-assays/