Abstract Number: PB0173
Meeting: ISTH 2022 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Basic
Background: The development of partially neutralizing anti-drug antibodies (ADA) might reduce emicizumab efficacy, but the effect on global coagulation assays is unknown.
Aims: To investigate the ability of non-activated thromboelastometry (NATEM) and thrombin generation assay (TGA), to reflect the biological effect of the presence of ADA.
Methods: We performed a cross-sectional study in patients with severe hemophilia A (HA) on emicizumab prophylaxis with and without partially neutralizing ADA. TGA was assessed with a homemade method upon addition of tissue-factor (1pM) and synthetic phospholipids (1µM) to plasma. Emicizumab plasma concentration (EmiC) was measured by a modified calibrated one stage FVIII assay, ADA were searched for with western blot method. NATEM was measured on citrated whole blood after addition of CaCl2 (100mM). Student’s T test for unpaired samples was used.
Results: Two patients aged 10 and 79, with persistent partially neutralizing ADA occurring after their 9th exposure, and 14 patients without ADA were enrolled. After 6 months of follow-up, the two patients with ADA and decreased EmiC reported no bleeding. Mean EmiC was 62.6 ug/ml in patients without ADA and 25.9 ug/ml in patients with ADA. When analyzing the coagulation with global assays in ADA patients, NATEM showed a delay in clot activation but the clotting formation was sustained and within the control range, as reported in Table 1 and Figure 1. When the TGA was carried out, the lagtime was not prolonged in comparison to controls, and again the endogenous thrombin potential and peak height were within control range, as shown in Table 1.
Conclusion(s): Our results show that despite decreased emicizumab level and prolonged aPTT, the coagulation of our patients was comparable to the controls when assessed with global coagulation tests, reflecting the absence of bleedings in vivo in two patients with ADA.
To cite this abstract in AMA style:
Arcudi S, Clerici M, Scalambrino E, Gualtierotti R, Nicolò G, Cafasso G, Biguzzi E, Novembrino C, Valsecchi C, Tripodi A, Peyvandi F. Global coagulation assays in hemophilic patients on emicizumab prophylaxis, with and without partially neutralizing anti-drug antibodies [abstract]. https://abstracts.isth.org/abstract/global-coagulation-assays-in-hemophilic-patients-on-emicizumab-prophylaxis-with-and-without-partially-neutralizing-anti-drug-antibodies/. Accessed March 21, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/global-coagulation-assays-in-hemophilic-patients-on-emicizumab-prophylaxis-with-and-without-partially-neutralizing-anti-drug-antibodies/