title: Safety of recombinant factor VIIa in patients under extracorporeal membrane oxygenation.
abstract: OBJECTIVE
  To address the safety (rate of thromboembolic events and circuit complications) and efficacy (rate of bleeding control) of recombinant activated coagulation factor VII (rFVIIa) to treat severe bleeding refractory to all surgical and medical treatments in patients under veno-arterial (VA) or veno-venous (VV) extracorporeal membrane oxygenation (ECMO) support.
  
  
  METHODS
  In a tertiary referral University Cardiothoracic Surgery Centre including three intensive care units, 30 patients received the rFVIIa during ongoing VA or VV ECMO support (8.6% of ECMO activity from 2005 to 2014; N = 347). Early and late clinical results were analysed (retrospective analysis of prospectively collected data). In a substudy, a case-matching procedure was performed among ECMO patients who received (Group A) or did not receive (Group B) rFVIIa treatment.
  
  
  RESULTS
  The mediastinum was the most common site of refractory bleeding (after heart transplantation or other cardiac surgery; 90%); 90% (n = 27) of patients were on VA ECMO and the remainder on VV ECMO. The survival rate at ECMO explantation and at the 30th post-implantation day was 67 and 50%, respectively. The final efficacy rate of rFVIIa in stopping bleeding was 93.3%. The rate of thromboembolic events was 3.3% (1 case) and the rate of circuit change was 16.7% (without instances of overt circuit clotting). After case-matching, Group A comprised 23 patients and Group B included 43 patients. No statistically significant differences were observed among groups in terms of thromboembolic events (P = 0.99), circuit change, ventilation time (P = 0.71), infectious complications (P = 06) and survival at both ECMO explantation and the 30th post-implantation day. Late survival was comparable (Kaplan-Meier analysis; P = 0.42).
  
  
  CONCLUSIONS
  In case of life-threatening bleeding refractory to all conventional therapies, rFVIIa presents an acceptable safety profile in patients under ECMO support. No circuit dysfunctions and limited rates of thromboembolism are observed.
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Pontchaillou University Hospital, Rennes, France INSERM (French National Institution for Healthcare and Medical Research) Unit 1099, University of Rennes 1, Rennes, France.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Anselmi
authors.affiliation: Division of Cardiac Anesthesia, Pontchaillou University Hospital, Rennes, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Guinet
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Pontchaillou University Hospital, Rennes, France INSERM (French National Institution for Healthcare and Medical Research) Unit 1099, University of Rennes 1, Rennes, France.
authors.forename: Vito Giovanni
authors.initials: VG
authors.lastname: Ruggieri
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Pontchaillou University Hospital, Rennes, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Aymami
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Pontchaillou University Hospital, Rennes, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Lelong
authors.affiliation: Pharmacology Unit, Pontchaillou University Hospital, Rennes, France.
authors.forename: Solène
authors.initials: S
authors.lastname: Granry
authors.affiliation: Department of Anesthesiology, Surgical Critical Care and Emergencies, Pontchaillou University Hospital, Rennes, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Malledant
authors.affiliation: Department of Medical Intensive Care Unit, Pontchaillou University Hospital, Rennes, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Tulzo
authors.affiliation: Department of Hematology, Pontchaillou University Hospital, Rennes, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gueret
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Pontchaillou University Hospital, Rennes, France INSERM (French National Institution for Healthcare and Medical Research) Unit 1099, University of Rennes 1, Rennes, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Verhoye
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Pontchaillou University Hospital, Rennes, France INSERM (French National Institution for Healthcare and Medical Research) Unit 1099, University of Rennes 1, Rennes, France erwan.flecher@chu-rennnes.fr.
authors.forename: Erwan
authors.initials: E
authors.lastname: Flecher
mesh_terms: D000328:Adult; D000368:Aged; D006348:Cardiac Surgical Procedures / Q000009:adverse effects / Q000379:methods*; D016022:Case-Control Studies; D016208:Databases, Factual; D015199:Extracorporeal Membrane Oxygenation / Q000009:adverse effects / Q000379:methods*; D015942:Factor VIIa / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000401:mortality / Q000601:surgery*; D006470:Hemorrhage / Q000139:chemically induced* / Q000401:mortality / Q000503:physiopathology; D017052:Hospital Mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D061214:Patient Safety / Q000706:statistics & numerical data*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D062606:Tertiary Care Centers; D013923:Thromboembolism / Q000517:prevention & control; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa
keywords: Bleeding; Extracorporeal membrane oxygenation; Outcomes