Frontiers in Medicine (Dec 2020)
Dabigatran Level Before Reversal Can Predict Hemostatic Effectiveness of Idarucizumab in a Real-World Setting
- Nicolas Gendron,
- Nicolas Gendron,
- Richard Chocron,
- Richard Chocron,
- Paul Billoir,
- Julien Brunier,
- Laurence Camoin-Jau,
- Marie Tuffigo,
- Dorothée Faille,
- Dorothée Faille,
- Dorian Teissandier,
- Juliette Gay,
- Juliette Gay,
- Emmanuelle de Raucourt,
- Emmanuelle de Raucourt,
- Ludovic Suner,
- Corentin Bonnet,
- Anne-Céline Martin,
- Anne-Céline Martin,
- Dominique Lasne,
- Chayma Ladhari,
- Aurélien Lebreton,
- Laurent Bertoletti,
- Laurent Bertoletti,
- Nadine Ajzenberg,
- Nadine Ajzenberg,
- Pascale Gaussem,
- Pascale Gaussem,
- Pierre-Emmanuel Morange,
- Pierre-Emmanuel Morange,
- Pierre-Emmanuel Morange,
- Véronique Le Cam Duchez,
- Alain Viallon,
- Pierre-Marie Roy,
- Pierre-Marie Roy,
- Agnès Lillo-le Louët,
- Agnès Lillo-le Louët,
- David M. Smadja,
- David M. Smadja,
- David M. Smadja
Affiliations
- Nicolas Gendron
- Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France
- Nicolas Gendron
- Hematology Department and Biosurgical Research Lab (Carpentier Foundation), AH-HP, Georges Pompidou European Hospital, Paris, France
- Richard Chocron
- Université de Paris, PARCC, INSERM, Paris, France
- Richard Chocron
- Emergency Department, AH-HP, Georges Pompidou European Hospital, Paris, France
- Paul Billoir
- Normandie Univ, UNIROUEN, INSERM Rouen University Hospital, Vascular Hemostasis Unit, Rouen, France
- Julien Brunier
- CHU-Pellegrin, Laboratory of Hematology, Bordeaux, France
- Laurence Camoin-Jau
- AP-HM, CHU Timone, Laboratory of Hematology, Marseille, France
- Marie Tuffigo
- CHU Angers, Laboratory of Hematology, Angers, France
- Dorothée Faille
- Université de Paris, Laboratory of Vascular Translational Science, INSERM, Paris, France
- Dorothée Faille
- 0Laboratory of Hematology, AH-HP, Bichat Hospital, Paris, France
- Dorian Teissandier
- 1CHU Clermont-Ferrand, Emergency Medicine Department, Clermont-Ferrand, France
- Juliette Gay
- Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France
- Juliette Gay
- 2Hematology Department, AH-HP, Georges Pompidou European Hospital, Paris, France
- Emmanuelle de Raucourt
- 3Université de Paris, LVTS, INSERM, Paris, France
- Emmanuelle de Raucourt
- 4Hematology Department, AP-HP, Hôpital Beaujon, Clichy, France
- Ludovic Suner
- 5Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, AP-HP, Hôpital Saint-Antoine, Hématologie Biologique, Paris, France
- Corentin Bonnet
- 6CHU Sud Réunion, Anaestesiology Department, Saint-Pierre, La Réunion, France
- Anne-Céline Martin
- Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France
- Anne-Céline Martin
- 7Cardiology Department, AH-HP, Georges Pompidou European Hospital, Paris, France
- Dominique Lasne
- 8AP-HP, CHU Necker-Enfants Malades, Department of Biogical Hematology, Paris, France
- Chayma Ladhari
- 9CHU Montpellier, Centre Régional de Pharmacovigilance, Montpellier, France
- Aurélien Lebreton
- 0CHU Clermont-Ferrand, Laboratory of Hematology, Clermont-Ferrand, France
- Laurent Bertoletti
- 1Service de Médecine Vasculaire et Thérapeutique, CHU de Saint-Étienne, INSERM, Université Jean-Monnet, INSERM, CHU de Saint-Étienne, Saint-Étienne, France
- Laurent Bertoletti
- 2F-CRIN INNOVTE, Saint-Étienne, France
- Nadine Ajzenberg
- Université de Paris, Laboratory of Vascular Translational Science, INSERM, Paris, France
- Nadine Ajzenberg
- 0Laboratory of Hematology, AH-HP, Bichat Hospital, Paris, France
- Pascale Gaussem
- Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France
- Pascale Gaussem
- 2Hematology Department, AH-HP, Georges Pompidou European Hospital, Paris, France
- Pierre-Emmanuel Morange
- AP-HM, CHU Timone, Laboratory of Hematology, Marseille, France
- Pierre-Emmanuel Morange
- 2F-CRIN INNOVTE, Saint-Étienne, France
- Pierre-Emmanuel Morange
- 3C2VN, Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France
- Véronique Le Cam Duchez
- Normandie Univ, UNIROUEN, INSERM Rouen University Hospital, Vascular Hemostasis Unit, Rouen, France
- Alain Viallon
- 4CHU Saint-Étienne, Emergency Department, Saint-Étienne, France
- Pierre-Marie Roy
- 2F-CRIN INNOVTE, Saint-Étienne, France
- Pierre-Marie Roy
- 5CHU Angers, Emergency Department and Vascular Medicine Ward, Université d'Angers, MITOVASC Institut, UMR (CNRS 6015—INSERM 1083), Angers, France
- Agnès Lillo-le Louët
- Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France
- Agnès Lillo-le Louët
- 6Département de Pharmacovigilance, AH-HP, Georges Pompidou European Hospital, Paris, France
- David M. Smadja
- Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France
- David M. Smadja
- Hematology Department and Biosurgical Research Lab (Carpentier Foundation), AH-HP, Georges Pompidou European Hospital, Paris, France
- David M. Smadja
- 2F-CRIN INNOVTE, Saint-Étienne, France
- DOI
- https://doi.org/10.3389/fmed.2020.599626
- Journal volume & issue
-
Vol. 7
Abstract
Background: Idarucizumab has been included in guidelines for the management of bleeding or surgical procedure in dabigatran-treated patients without need for biological monitoring. The aim of the study was to assess the prognostic value of dabigatran plasma level before reversal to test the hemostatic efficacy of idarucizumab. The secondary objectives were (i) to analyze plasma dabigatran level according to the risk of rebound and (ii) to evaluate the incidence of post-reversal non-favorable clinical outcomes (including thromboembolism, bleeding, antithrombotic, and death) and antithrombotic resumption.Methods and Results: This was an observational multicentric cohort study, which included all French patients who required idarucizumab for dabigatran reversal. Between May 2016 and April 2019, 87 patients from 21 French centers were enrolled. Patients received idarucizumab for overt bleeding (n = 61), urgent procedures (n = 24), or overdose without bleeding (n = 2). Among patients with major bleeding (n = 57), treatment with idarucizumab was considered effective in 44 (77.2%) of them. Patients who did not achieve effective hemostasis after reversal had a significantly higher mean level of plasma dabigatran at baseline (524.5 ± 386 vs. 252.8 ng/mL ± 235, p = 0.033). Furthermore, patients who did not achieve effective hemostasis after reversal had less favorable outcomes during follow-up (46.2 vs. 81.8%, p = 0.027). ROC curve identified a cutoff of 264 ng/mL for dabigatran level at admission to be predictive of ineffective hemostasis. No plasma dabigatran rebound was observed after reversal in patients with dabigatran plasma level < 264 ng/mL at baseline.Conclusion: This retrospective study shows that dabigatran level before reversal could predict hemostatic effectiveness and dabigatran plasma rebound after idarucizumab injection.
Keywords