Anne Godier1, Anne-Céline Martin2, Isabelle Leblanc3, Elisabeth Mazoyer4, Marie-Hélène Horellou5, Firas Ibrahim6, Claire Flaujac6, Jean-Louis Golmard7, Nadia Rosencher8, Isabelle Gouin-Thibault9. 1. Fondation Rothschild, Service d'Anesthésie-Réanimation, Paris, France; Inserm UMR-S1140, Faculté de Pharmacie, Paris, France. Electronic address: agodier@fo-rothschild.fr. 2. Inserm UMR-S1140, Faculté de Pharmacie, Paris, France; Hôpital Val de Grâce, Service de Cardiologie, Paris, France. 3. Institut Mutualiste Montsouris, Service d'Anesthésie, Paris, France. 4. AP-HP, Hôpital Avicenne, Laboratoire d'hématologie, Bobigny, France. 5. AP-HP, Hôpital Cochin, Laboratoire d'hématologie, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 6. AP-HP, Hôpital Cochin, Laboratoire d'hématologie, Paris, France. 7. AP-HP, GH Pitié-Salpêtrière, Département de biostatistiques, Paris, France. 8. AP-HP, Hôpital Cochin, Service d'Anesthésie-Réanimation, Paris, France. 9. Inserm UMR-S1140, Faculté de Pharmacie, Paris, France; AP-HP, Hôpital Cochin, Laboratoire d'hématologie, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Abstract
BACKGROUND: Peri-procedural management of direct oral anticoagulants (DOAC) is challenging. The optimal duration of pre-procedural discontinuation that guarantees a minimal DOAC concentration ([DOAC]) at surgery is unknown. The usual 48-hour discontinuation might not be sufficient for all patients. OBJECTIVES: To test the hypothesis that a 48-hour DOAC discontinuation is not sufficient to ensure a minimal per-procedural [DOAC], defined as [DOAC]<30ng/mL. To investigate the factors associated with per-procedural [DOAC]. To evaluate the ability of normal PT and aPTT to predict [DOAC]<30ng/mL. METHODS: Patients treated with dabigatran or rivaroxaban, and requiring any invasive procedure were included in this multicentre, prospective, observational study. [DOAC], PT and aPTT were measured during invasive procedure. RESULTS: Sixty-five patients were enrolled. Duration of DOAC discontinuation ranged from 1-168h. Per-procedural [DOAC] ranged from <30 to 466ng/mL. [DOAC]<30ng/mL occurred more frequently after 48-hour discontinuation than after a shorter delay. [DOAC] remained ≥30ng/mL in 36% and 14% of measurements performed 24-48h and 48h-120h after discontinuation, respectively. According to ROC curve, a cut-off value of 120hours for DOAC discontinuation had a better specificity than a cut-off value of 48hours to predict [DOAC]<30ng/mL. Normal PT and aPTT ratios had good specificity and positive predictive value, but limited sensitivity (74%) and negative predictive value (73%) to predict [DOAC]<30ng/mL. CONCLUSIONS: A 48-hour discontinuation does not guarantee a [DOAC]<30ng/mL in all patients. Normal PT and aPTT are flawed to predict this threshold and could not replace specific assays. Further studies are needed to define the relationship between per-procedural [DOAC] and clinical outcomes.
BACKGROUND: Peri-procedural management of direct oral anticoagulants (DOAC) is challenging. The optimal duration of pre-procedural discontinuation that guarantees a minimal DOAC concentration ([DOAC]) at surgery is unknown. The usual 48-hour discontinuation might not be sufficient for all patients. OBJECTIVES: To test the hypothesis that a 48-hour DOAC discontinuation is not sufficient to ensure a minimal per-procedural [DOAC], defined as [DOAC]<30ng/mL. To investigate the factors associated with per-procedural [DOAC]. To evaluate the ability of normal PT and aPTT to predict [DOAC]<30ng/mL. METHODS:Patients treated with dabigatran or rivaroxaban, and requiring any invasive procedure were included in this multicentre, prospective, observational study. [DOAC], PT and aPTT were measured during invasive procedure. RESULTS: Sixty-five patients were enrolled. Duration of DOAC discontinuation ranged from 1-168h. Per-procedural [DOAC] ranged from <30 to 466ng/mL. [DOAC]<30ng/mL occurred more frequently after 48-hour discontinuation than after a shorter delay. [DOAC] remained ≥30ng/mL in 36% and 14% of measurements performed 24-48h and 48h-120h after discontinuation, respectively. According to ROC curve, a cut-off value of 120hours for DOAC discontinuation had a better specificity than a cut-off value of 48hours to predict [DOAC]<30ng/mL. Normal PT and aPTT ratios had good specificity and positive predictive value, but limited sensitivity (74%) and negative predictive value (73%) to predict [DOAC]<30ng/mL. CONCLUSIONS: A 48-hour discontinuation does not guarantee a [DOAC]<30ng/mL in all patients. Normal PT and aPTT are flawed to predict this threshold and could not replace specific assays. Further studies are needed to define the relationship between per-procedural [DOAC] and clinical outcomes.
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