title: Adverse events and clinical outcome associated with drotrecogin alfa-activated: a single-center experience of 498 patients over 8 years.
abstract: OBJECTIVE
  Licensed in 2002 for severe sepsis, drotrecogin alfa-activated (DAA) remains a much debated therapy particularly with respect to outcomes and a potentially increased risk of serious bleeding events (SBEs). Recent publications have suggested a significantly increased incidence of SBEs and death in those with baseline bleeding risks (BBRs). Our center is one of the highest prescribers of DAA worldwide; we describe our experience of SBEs and other clinical outcomes.
  
  
  METHODS
  Prospectively collected data using a clinical guideline audit tool and database to track outcome and adverse events of DAA-treated severe sepsis patients were analyzed.
  
  
  RESULTS
  Four hundred ninety-eight patients received DAA over an 8-year period. Hospital, critical care, and 28-day mortalities were 46.2%, 39.6%, and 35.1%, respectively. Contraindications were identified for 40 (8.0%) patients, of whom 24 (4.8%) had BBRs. Hospital mortality was 47.5% (19/40) for patients with any contraindication and 45.8% (11/24) for those with a BBR. Seventy-six (15.3%) bleeding events were reported; 22 (4.4%) were considered serious. Hospital mortality was 60.5% for patients with any bleeding event and 77.3% for those with SBEs.
  
  
  CONCLUSIONS
  This large single-center case series demonstrates that DAA has an incidence of SBEs similar to initial clinical trials. As expected, SBEs were associated with a poor outcome.
authors.affiliation: Institute of Pharmaceutical Sciences, Kings College London and Department of Pharmacy and Critical Care, St Thomas' Hospital, London SE1 7EH, UK. alisonboyle_1@hotmail.com
authors.forename: Alison
authors.initials: A
authors.lastname: Boyle
authors.forename: Cathrine
authors.initials: C
authors.lastname: McKenzie
authors.forename: Sarah
authors.initials: S
authors.lastname: Yassin
authors.forename: Angela
authors.initials: A
authors.lastname: McLuckie
authors.forename: Duncan
authors.initials: D
authors.lastname: Wyncoll
mesh_terms: D000890:Anti-Infective Agents / Q000009:adverse effects*; D000075202:Contraindications; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology*; D017052:Hospital Mortality; D006801:Humans; D015994:Incidence; D008131:London / Q000453:epidemiology; D008297:Male; D008485:Medical Audit; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000188:drug therapy / Q000401:mortality; D018579:Patient Selection; D011446:Prospective Studies; D011486:Protein C / Q000009:adverse effects*; D011994:Recombinant Proteins / Q000009:adverse effects; D018570:Risk Assessment; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis
chemical_list: D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated