title: Peri-procedural management of dabigatran and rivaroxaban: Duration of anticoagulant discontinuation and drug concentrations.
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.
  
  
  OBJECTIVE
  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.
authors: Fondation Rothschild, Service d'Anesthésie-Réanimation, Paris, France; Inserm UMR-S1140, Faculté de Pharmacie, Paris, France. Electronic address: agodier@fo-rothschild.fr.
authors: Anne
authors: A
authors: Godier
authors: Inserm UMR-S1140, Faculté de Pharmacie, Paris, France; Hôpital Val de Grâce, Service de Cardiologie, Paris, France.
authors: Anne-Céline
authors: AC
authors: Martin
authors: Institut Mutualiste Montsouris, Service d'Anesthésie, Paris, France.
authors: Isabelle
authors: I
authors: Leblanc
authors: AP-HP, Hôpital Avicenne, Laboratoire d'hématologie, Bobigny, France.
authors: Elisabeth
authors: E
authors: Mazoyer
authors: AP-HP, Hôpital Cochin, Laboratoire d'hématologie, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors: Marie-Hélène
authors: MH
authors: Horellou
authors: AP-HP, Hôpital Cochin, Laboratoire d'hématologie, Paris, France.
authors: Firas
authors: F
authors: Ibrahim
authors: AP-HP, Hôpital Cochin, Laboratoire d'hématologie, Paris, France.
authors: Claire
authors: C
authors: Flaujac
authors: AP-HP, GH Pitié-Salpêtrière, Département de biostatistiques, Paris, France.
authors: Jean-Louis
authors: JL
authors: Golmard
authors: AP-HP, Hôpital Cochin, Service d'Anesthésie-Réanimation, Paris, France.
authors: Nadia
authors: N
authors: Rosencher
authors: 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.
authors: Isabelle
authors: I
authors: Gouin-Thibault
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use; D000991:Antithrombins / Q000008:administration & dosage / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D000069604:Dabigatran / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D000069552:Rivaroxaban; D000069604:Dabigatran
keywords: Anti-IIa; Anti-Xa; Anticoagulant; PT; Surgery; aPTT