A comprehensive multicenter study assessing the impact of abelacimab, asundexian, and milvexian on coagulation assays
Year: 2026
Type: article
Abstract: ABSTRACT: Phase 3 trials evaluating inhibitors of coagulation factor XI (FXI) and/or its activated form (FXIa) as novel anticoagulant drugs are ongoing. These agents include parenteral monoclonal antibody (abelacimab) and oral small molecules (milvexian, asundexian). We investigated the extent to which standard and specialized coagulation assays are affected by FXI(a) inhibitors in a multicenter study involving 23 laboratories. FXI(a) inhibitors were spiked into pooled normal plasma at concentrations covering those observed in phase 2/3 clinical trials: 50 to 2000 ng/mL for milvexian and asundexian, and 1 to 30 μg/mL for abelacimab. Actual plasma concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Assays were performed blindly using 5 to 11 different combinations of reagent/analyzer depending on the assay. Prothrombin time, Clauss fibrinogen, and clotting activity of FII, FV, FVII, and FX were not affected in a clinically relevant manner. Activated partial thromboplastin time (aPTT) was prolonged in a concentration-dependent manner, with milvexian having the greatest impact followed by abelacimab and asundexian. Clotting activity of FVIII, FIX, FXI, and FXII was underestimated. Such interference was prevented by high plasma dilution (up to 1:160) before the test, except for abelacimab: FXI clotting activity remained decreased, even at low concentration (2.5 μg/mL). FXI(a) inhibitors did not affect lupus anticoagulant (LA) testing using dilute Russell viper venom time but may lead to false-negative result with LA-sensitive aPTT reagents. Protein C anticoagulant activity was overestimated, whereas no impact on protein S anticoagulant activity was observed. This study provides a comprehensive laboratory framework for interpreting clotting assays in future patients receiving FXI(a) inhibitors.
Source: Blood Advances
Authors: Laurie Goubeau, Emmanuel Curis, Xavier Delavenne, Isabelle Gouin-Thibault, Sophie Hodin, Adrien Genin, Julien Demagny, Fanny Menard, Dorothée Faille, Christine Mouton, Emmanuel De Maistre, Pierre Fontana, Laetitia Mauge, Annabelle Dupont, Christophe Nougier, Nathalie Hézard, Elodie Boissier, Dominique Lasne, François Grand, Paul Billoir, Agathe Herb, Corinne Frere, Sophie Voisin, Nicolas Sillamy, Claire Flaujac, François Mullier, Virginie Siguret, Georges Jourdi
Institutions: Assistance Publique – Hôpitaux de Paris, Hôpital Lariboisière, Université Paris Cité, Biostatistique, traitement et modélisation des données biologiques, Inserm, Centre Hospitalier Universitaire de Saint-Étienne, École des Hautes Études en Santé Publique, Institut de Recherche en Santé, Environnement et Travail, Hôpital Pontchaillou, Université de Rennes, Centre Hospitalier Intercommunal Aix-Pertuis, Centre Hospitalier Universitaire Amiens-Picardie, Hématopoïèse et immunologie, Université de Picardie Jules Verne, Centre Hospitalier de la Côte Basque, Hôpital Bichat-Claude-Bernard, Optimisation Thérapeutique en Neuropsychopharmacologie, Centre Hospitalier Universitaire de Bordeaux, Hôpital Cardiologique du Haut-Lévêque, CHU Dijon Bourgogne, University Hospital of Geneva, Hôpital Européen Georges-Pompidou, Paris Cardiovascular Research Center, Université de Lille, Institut Pasteur de Lille, Centre Hospitalier Universitaire de Lille, Hospices Civils de Lyon, Assistance Publique Hôpitaux de Marseille, Hôpital de la Timone, Centre Hospitalier Universitaire de Nantes, Nantes Université, Hôpital Necker-Enfants Malades, Centre Hospitalier Universitaire de Poitiers, Endothélium, valvulopathies et insuffisance cardiaque, Centre Hospitalier Universitaire de Rouen, Université de Rouen Normandie, Hôpitaux Universitaires de Strasbourg, Sorbonne Université, Fondation pour l’innovation en Cadiométabolisme et Nutrition, Hôpital Tenon, Centre Hospitalier Universitaire de Toulouse, Centre Hospitalier Universitaire de Tours, Hôpital André Mignot, Centre Hospitalier de Versailles, Namur Research Institute for Life Sciences, UCLouvain
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
OpenAlex ID: W7162507925