Abstract Number: PB1164
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Novel Biotherapeutics in Hemophilia
Background: Emicizumab, a humanized bispecific antibody that activates factor X in the absence of factor VIII (FVIII), has improved convenience for hemophilia A prophylaxis and decreased annualized bleeding rates (ABR); however, the use of laboratory assays to confirm hemostatic efficacy and predict outcomes has not been explored.
Aims: To measure factor Xa and thrombin generation and compare them to hemostatic efficacy of emicizumab.
Methods: Data regarding age, inhibitor status, ABR, and Hemophilia Joint Health Scores (HJHS) were extracted from a consented cohort study (HemoPICS) of persons with hemophilia A (PwHA) on emicizumab. Samples from the cohort biobank were used in a chromogenic FVIII assay (Human BIOPEN FVIIIC Hyphen, BioMed) and the Calibrated Automated Thrombogram (CAT, Stago); both assays were performed according to manufacturers’ instructions. Age-stratified reference ranges were derived on 46 healthy adults and 17 children. Pre-emicizumab samples were from time of FVIII trough. Data were analyzed using correlations, related samples Wilcoxon signed rank tests (pre-to post-emicizumab), and Mann-Whitney U tests (+ vs – inhibitor on emicizumab).
Results: Data from 33 PwHA were analyzed. At emicizumab start, 7 participants had active inhibitors, 26 did not. Figure 1 shows that the CAT endogenous thrombin potential (ETP, area under the curve), thrombin peak and chromogenic FVIII all increased significantly and similarly in both inhibitor positive and negative PwHA on emicizumab. Laboratory results did not correlate with outcomes except for non-significant trends (p = 0.05-0.1) between CAT peak thrombin and ABR. The lack of correlation between any assay parameter and ABR or HJHS is not unexpected given the similar laboratory responses, low bleeding rate, small sample size and short duration of observation.
Conclusions: Following adoption of emicizumab, samples from PwHA showed a significant increase in CAT ETP, CAT thrombin peak and chromogenic FVIII. More data are needed to determine if these assays correlate with outcomes.
[Figure 1. Endogenous thrombin potential, thrombin peak and chromogenic FVIII with human reagents in PwHA on Emicizumab.]
To cite this abstract in AMA style:
Moyer G, Warren BB, Jacobson L, Baird CH, Thornhill D, Smith J, Ng C, Buckner TW, Branchford B, Wang M, Manco-Johnson MJ. Emicizumab beyond Annualized Bleeding Rate: Do Laboratory Assays Help Predict Emicizumab Effects? [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/emicizumab-beyond-annualized-bleeding-rate-do-laboratory-assays-help-predict-emicizumab-effects/. Accessed October 2, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/emicizumab-beyond-annualized-bleeding-rate-do-laboratory-assays-help-predict-emicizumab-effects/