Background: In previous studies, we demonstrated that abelacimab does not affect platelet function; concomitant use of abelacimab with antiplatelet drugs was not previously evaluated.

Aims: To assess the effects of increasing concentrations of abelacimab on the inhibition of platelet aggregation by aspirin or ticagrelor.

Methods: We concurrently conducted 2 studies. Blood specimens were obtained in EDTA and citrate tubes (6 healthy donors for each study). In the first study, whole blood was spiked with vehicle, aspirin (1 mg/mL), or aspirin (1 mg/mL) + abelacimab (125, 250, and 500 nM). Platelet aggregation was measured by impedance platelet aggregometry following induction with collagen (3.2 µg/mL) or arachidonic acid (0.5 mM) (Multiplate® analyzer, COLtest and ASPItest reagents; Roche Diagnostics International Ltd, Rotkreuz, Switzerland).

In the second study, whole blood was spiked with vehicle, ticagrelor (3 µM), or ticagrelor (3 µM) + abelacimab (125, 250, and 500 nM). Platelet aggregation was measured with the same methodology following induction by ADP (6.4 µM) or thrombin receptor activating peptide-6 (TRAP-6; 32 µM).

Results: In the presence of aspirin, platelet aggregation induced with collagen or arachidonic acid was inhibited by 60% and 71%, respectively (p < 0.05). Abelacimab at 125, 250, and 500 ng/mL did not attenuate or increase the level of inhibition achieved with aspirin alone (Figure 1). In presence of ticagrelor, platelet aggregation induced with ADP or TRAP-6 was inhibited by 54% and 31%, respectively (p < 0.05). Abelacimab at 125, 250, and 500 ng/mL did not alter platelet inhibition achieved with ticagrelor alone (Figure 2).

Conclusion(s): Abelacimab at clinically relevant concentrations did not alter the inhibitory effects of aspirin or ticagrelor. These results suggest that pharmacodynamic interactions between abelacimab and two commonly used antiplatelet agents are unlikely.

Image

In vitro effect of abelacimab -MAA868- combined with aspirin -ASA- on whole blood platelet aggregometry induced with 3.2 µg/mL collagen -Panel A- or with 0.5 mM arachidonic acid -Panel B-

Image

In vitro effect of abelacimab -MAA868- combined with ticagrelor on whole blood platelet aggregometry induced with 6.4 µM ADP -Panel A- or with 32 µM TRAP6 -Panel B-

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/abelacimab-does-not-influence-the-effects-of-two-commonly-used-antiplatelet-agents-in-vitro/