Impact of asundexian on a panel of coagulation assays

Résumé fourni par la source

Background: During the last few years, the small, oral, activated factor XI inhibitor, asundexian, has been investigated in different cardiovascular disorders. However, little is known about its impact on laboratory coagulation assays. Objectives: To describe the effects of asundexian on a panel of laboratory coagulation assays. Methods: The following assays were performed in normal pooled plasma spiked with increasing concentrations of asundexian (0-2000 ng/mL): activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen quantification (PT-derived and Clauss method), one-stage aPTT and PT-based coagulation factor assays, chronometric protein C and immunoturbidimetric protein S assays, reptilase time, chromogenic ecarin assay, dilute Russell's viper venom time assays, thrombin generation assay initiated by tissue factor (1, 5, and 20 pM) and ellagic acid (0.42 μM), rotational thromboelastometry intrinsically- and extrinsically-triggered assays, kaolin-activated clotting time, and glass bead-activated clotting time. This latter assay was also carried out in whole blood. Results: Asundexian up to 2000 ng/mL impacted aPTT and one-stage aPTT-based coagulation factor assays, with high variability between reagents and methodologies. Asundexian reduced thrombin generation triggered by ellagic acid and 1 or 5 pM tissue factor. The rotational thromboelastometry intrinsically-triggered assays and kaolin- and glass bead-activated clotting time assays were affected by asundexian 2000 ng/mL, while overall, no significant interference was observed with any of the remaining assays. Conclusion: Despite this study including a comprehensive panel of coagulation assays, asundexian may still affect other coagulation assays not assessed here. Further investigations in patients treated with asundexian are therefore warranted.

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