title: Prognostic factors of hemorrhagic complications after oxaliplatin-based hyperthermic intraperitoneal chemotherapy: Toward routine preoperative dosage of Von Willebrand factor?
abstract: BACKGROUND
  Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC-ox) induces specific morbidity with hemorrhagic complications (HC). The aim of this study was to identify preoperative, intraoperative and postoperative HC predictive factors after HIPEC-ox.
  
  
  METHODS
  A prospective single center study that included all consecutive patients treated with curative-intent HIPEC-ox, whatever the origin of peritoneal disease, was conducted. All patients underwent systematic blood tests exploring primary hemostasis and endothelial activation before surgical incision (D0) and on postoperative days 2 (POD2) and 5 (POD5).
  
  
  RESULTS
  Between May 2012 and August 2015, 47 patients were enrolled in the study. The overall HC rate was 38%. Major morbidity was significantly higher in patients with HC. Patients presenting HC were significantly more often affected with pseudomyxoma peritonei and had less preoperative chemotherapy. Multivariate analysis showed that a higher plasmatic level of Von Willebrand factor antigen at D0 (D0 VWF:Ag) was a protective predictive factor for HC (p = 0.049, HR: 0.97 CI 95% [0.94-1.00]). A D0 VWF:Ag level below 138% had a sensitivity of 87.5%, a specificity of 67% and an area under the curve of 80.3% (CI 95% [66.5-94], p < 0.01) for predicting HC.
  
  
  CONCLUSIONS
  Through the identification of prognostic factors, this study highlighted a subgroup of patients with low risk of HC after HIPEC-ox. Based on these results, we propose a routine preoperative dosage of VWF that would help the surgeon to select the most suitable patients for HIPEC-ox.
authors.affiliation: Department of General and Digestive Surgery, Hautepierre Hospital, Strasbourg University Hospital, 2 avenue Molière, 67200, Strasbourg, France; INSERM UMR_S1113, Université de Strasbourg, FMTS, 3 avenue Molière, 67200, Strasbourg, France. Electronic address: jean-baptiste.delhorme@chru-strasbourg.fr.
authors.forename: J-B
authors.initials: JB
authors.lastname: Delhorme
authors.affiliation: Biological Hematology Laboratory, Hemostasis Unit, Strasbourg University Hospital, 2 avenue Molière, 67200, Strasbourg, France.
authors.forename: L
authors.initials: L
authors.lastname: Sattler
authors.affiliation: Department of Public Health, Strasbourg University Hospital, 1 place de l'hôpital BP426, 67091, Strasbourg, France.
authors.forename: F
authors.initials: F
authors.lastname: Severac
authors.affiliation: Department of General and Digestive Surgery, Hautepierre Hospital, Strasbourg University Hospital, 2 avenue Molière, 67200, Strasbourg, France.
authors.forename: E
authors.initials: E
authors.lastname: Triki
authors.affiliation: INSERM UMR_S1113, Université de Strasbourg, FMTS, 3 avenue Molière, 67200, Strasbourg, France.
authors.forename: I
authors.initials: I
authors.lastname: Gross
authors.affiliation: Department of General and Digestive Surgery, Hautepierre Hospital, Strasbourg University Hospital, 2 avenue Molière, 67200, Strasbourg, France.
authors.forename: B
authors.initials: B
authors.lastname: Romain
authors.affiliation: Department of General and Digestive Surgery, Hautepierre Hospital, Strasbourg University Hospital, 2 avenue Molière, 67200, Strasbourg, France.
authors.forename: S
authors.initials: S
authors.lastname: Rohr
authors.affiliation: Biological Hematology Laboratory, Hemostasis Unit, Strasbourg University Hospital, 2 avenue Molière, 67200, Strasbourg, France.
authors.forename: L
authors.initials: L
authors.lastname: Grunebaum
authors.affiliation: Department of General and Digestive Surgery, Hautepierre Hospital, Strasbourg University Hospital, 2 avenue Molière, 67200, Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Brigand
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy; D065426:Cytoreduction Surgical Procedures; D004844:Epistaxis / Q000453:epidemiology / Q000378:metabolism / Q000517:prevention & control; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000453:epidemiology / Q000378:metabolism / Q000517:prevention & control; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007263:Infusions, Parenteral; D007414:Intestinal Neoplasms / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D010532:Peritoneal Diseases / Q000453:epidemiology / Q000378:metabolism / Q000517:prevention & control; D010534:Peritoneal Neoplasms / Q000556:secondary / Q000628:therapy*; D019106:Postoperative Hemorrhage / Q000453:epidemiology* / Q000378:metabolism / Q000517:prevention & control; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D014594:Uterine Neoplasms / Q000473:pathology / Q000628:therapy; D014841:von Willebrand Factor / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: D009944:Organoplatinum Compounds; D014841:von Willebrand Factor; D000077150:Oxaliplatin
keywords: Chemotherapy; HIPEC; Hemorrhagic complication; Oxaliplatin; Von Willebrand factor