title: Once versus twice daily injection of enoxaparin for thromboprophylaxis in bariatric surgery: effects on antifactor Xa activity and procoagulant microparticles. A randomized controlled study.
abstract: BACKGROUND
  The optimal scheme of thromboprophylaxis in bariatric surgery remains uncertain, because clinical practice is different between countries and randomized trials are lacking.
  
  
  OBJECTIVE
  The primary objective of this randomized multicenter study was to determine the optimal regimen of enoxaparin providing an antifactor Xa peak activity between .3 and .5 IU/mL at equilibrium and to evaluate the course of procoagulant microparticles (MPs).
  
  
  METHODS
  University hospital.
  
  
  METHODS
  A total of 164 patients scheduled for gastric bypass were allocated to 3 groups (A, B, and C) of enoxaparin treatment (4000, 6000, or 2×4000 IU, respectively). Antifactor Xa activity was measured before and 4 hours after each injection from D0 to D2. Doppler screening of the lower limbs was performed at D1, D9, and D30. Bleeding (BE) and thrombotic events (TE) were recorded during the first postoperative month. Total MPs were measured at D0, D9, and D30. MPs of leucocyte, platelet, and granulocyte origin were assessed in one third of the patients from each group. The 3 groups were compared by ANOVA.
  
  
  RESULTS
  A total of 135 patients were analyzed. The equilibrium of antifactor Xa peak levels was obtained 52 hours after the presurgery injection and 12.8%, 56.4%, and 27.3% of the patients reached the target in groups A, B, and C, respectively (P<.001). No TE was detected. BE occurred in 1, 2, and 6 patients in groups A, B, and C, respectively). Total MPs remained unchanged over time. While no significant variation was observed in the other groups, platelet GP1 b(+)-MPs increased (P = .01) at D9 in group C, suggesting an incomplete control of anticoagulation leading to cell activation and procoagulant MP release that was confirmed by the higher MP levels measured at D30 (P = .04). CD66(+)-MPs were also highly elevated at J9 and D30 in group C indicating a granulocyte contribution.
  
  
  CONCLUSIONS
  This study shows that a single dose of enoxaparin 6000 IU/d allowed most of the patients to reach the target range of antifactor Xa activity without increasing the bleeding risk, with the most likely efficient reduction of procoagulant MPs. (Surg Obes Relat Dis 2015;0:000-000.) © 2015 American Society for Metabolic and Bariatric Surgery. All rights reserved.
authors.affiliation: Department of Anesthesiology and Intensive Care, Nouvel Hopital Civil, University of Strasbourg, Federation Médecine Translationnelle, Strasbourg, France. Electronic address: annick.steib@chru-strasbourg.fr.
authors.forename: Annick
authors.initials: A
authors.lastname: Steib
authors.affiliation: Department of Anesthesiology and Intensive Care, Nouvel Hopital Civil, University of Strasbourg, Federation Médecine Translationnelle, Strasbourg, France.
authors.forename: Su-Emmanuelle
authors.initials: SE
authors.lastname: Degirmenci
authors.affiliation: Department of Anesthesiology, University Hospital Brabois, Vandoeuvre les Nancy, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Junke
authors.affiliation: Department of Anesthesiology, University Hospital Hôtel Dieu, Nantes, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Asehnoune
authors.affiliation: Department of Anesthesiology and Intensive Care, Nouvel Hopital Civil, University of Strasbourg, Federation Médecine Translationnelle, Strasbourg, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Figier
authors.affiliation: Department of Anesthesiology and Intensive Care, Nouvel Hopital Civil, University of Strasbourg, Federation Médecine Translationnelle, Strasbourg, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pericard
authors.affiliation: Department of Digestive Surgery, University Hospital Hautepierre, Strasbourg, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Rohr
authors.affiliation: Department of Digestive Surgery, University Hospital Hôtel Dieu, Nantes, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Letessier
authors.affiliation: Department of Digestive Surgery, University Hospital Brabois, Vandoeuvre, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Brunaud
authors.affiliation: Department of General Surgery, University Hospital, NHC, Strasbourg, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Vix
authors.affiliation: Faculty of Medicine, EA 7893, University of Strasbourg, Strasbourg, France.
authors.forename: Fatiha
authors.initials: F
authors.lastname: Zobairi
authors.affiliation: Laboratory of Hemostasis, University Hospital Strasbourg, Strasbourg, France.
authors.forename: Lelia
authors.initials: L
authors.lastname: Grunebaum
authors.affiliation: Faculty of Pharmacy, UMR CNRS 7213, University of Strasbourg, Strasbourg, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Toti
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D055252:Cell-Derived Microparticles / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D017984:Enoxaparin / Q000008:administration & dosage* / Q000009:adverse effects; D065427:Factor Xa Inhibitors / Q000378:metabolism*; D005260:Female; D015390:Gastric Bypass / Q000009:adverse effects / Q000379:methods; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D009767:Obesity, Morbid / Q000601:surgery; D011182:Postoperative Care / Q000379:methods; D011183:Postoperative Complications / Q000517:prevention & control; D011300:Preoperative Care / Q000379:methods; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors
keywords: Anticoagulation; Bariatric surgery; Microparticles; Prophylaxis; Venous thromboembolism