Background: Factor XI (FXI) has been identified as a ligand to ApoER2 and GPIbα on the surface of stimulated platelets. The impact of FXI inhibition by abelacimab on platelet aggregation remains to be determined.

Aims: To test the effects of increasing concentrations of abelacimab on platelet aggregation following stimulation with collagen or thrombin receptor activating peptide-6 (TRAP-6) compared with vehicle and active control (abciximab, anti-GP2b3a) and to determine the effects of both agents on thrombin generation.

Methods: Whole blood was obtained in EDTA and citrate tubes (6 healthy donors). Specimens were spiked with vehicle, abelacimab (250, 500, or 1000 nM), or abciximab (50 nM). Platelet aggregation was recorded following induction using collagen (1 µg/mL) or TRAP-6 (8 µM using a Multiplate® impedance aggregometer (Roche Diagnostics International Ltd, Switzerland). The area under the curve (AUC) for platelet aggregation was determined in arbitrary aggregation*time (AU*min). Thrombin generation was also measured at the above abelacimab and abciximab concentrations in platelet-rich plasma using Thrombinoscope CAT (Calibrated Automated Thrombogram; Stago CH S.A.) and tissue factor reagent (1 pM); fluorescence was measured by an automated plate reader fluorometer (Fluoroskan Ascent, Thermolabsystems, Helsinki, Finland).

Results: Abelacimab showed no inhibitory or stimulatory effects on platelet aggregation induced by collagen or TRAP-6 (Figure 1). In contrast, significant reductions in collagen-induced platelet aggregation were observed with abciximab. Abelacimab resulted in significant delays in lag time and the time to peak concentration of thrombin generation; abciximab had no effect on thrombin generation.

Conclusion(s): Targeting FXI/FXIa by abelacimab does not affect platelet aggregation. However, abelacimab had an inhibitory effect on thrombin generation. As expected, abciximab inhibited collagen-induced platelet aggregation but did not affect thrombin generation.

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In vitro effects of abelacimab -MAA868- on whole blood platelet aggregation induced with collagen and TRAP-6

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/abelacimab-has-no-effect-on-platelet-aggregation-induced-by-trap-6-and-collagen/