title: An open-label, randomized, parallel-group study of perioperative epoetin alfa versus standard of care for blood conservation in major elective spinal surgery: safety analysis.
abstract: METHODS
  Prospective, open-label, randomized, parallel-group study at 80 centers.
  
  
  OBJECTIVE
  To demonstrate there is no clinically important additional risk for deep vein thrombosis with perioperative use of epoetin alfa versus standard of care in spine surgery without prophylactic anticoagulation.
  
  
  BACKGROUND
  Trials of epoetin alfa in orthopedic surgery that demonstrated no additional risk of thrombovascular events included perioperative pharmacologic anticoagulation.
  
  
  METHODS
  Subjects received epoetin alfa 600 U/kg subcutaneously once weekly starting 3 weeks before spinal surgery plus standard of care for blood conservation, or standard of care alone. Perioperative anticoagulation therapy was not permitted; mechanical deep vein thrombosis prophylaxis was allowed. Doppler imaging for deep vein thrombosis was done on postoperative day 4 (or day of discharge), or for suspected deep vein thrombosis. Deep vein thrombosis was diagnosed by Doppler result or adverse event report. The criterion for no additional risk of deep vein thrombosis was a 1-sided 97.5% upper confidence limit < or =4% between groups.
  
  
  RESULTS
  Of the 680 subjects analyzed (340 in each treatment group), 16 (4.7%) in the epoetin alfa group and 7 (2.1%) in the standard of care group had a diagnosis of deep vein thrombosis either by Doppler or by adverse event report with normal Doppler. The between-group difference was 2.6% (97.5% upper confidence limit, 5.4%). Deep vein thrombosis confirmed by Doppler (4.1% vs. 2.1%), other clinically relevant thrombovascular events (1.5% vs. 0.9%), and all adverse events combined (76.5% vs. 73.2%) occurred with similar frequency in the 2 treatment groups.
  
  
  CONCLUSIONS
  This study documented a higher incidence of deep vein thrombosis and similar rates of other clinically relevant thrombovascular events with epoetin alfa versus standard of care for blood conservation in subjects who did not receive prophylactic anticoagulation before spinal surgery. Antithrombotic prophylaxis should be considered when erythropoietin is used in the surgical setting.
authors.affiliation: Blood Transfusion Service, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. cstowell@partners.org
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Stowell
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Jones
authors.forename: Christopher
authors.initials: C
authors.lastname: Enny
authors.forename: Wayne
authors.initials: W
authors.lastname: Langholff
authors.forename: Gerhard
authors.initials: G
authors.lastname: Leitz
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D017558:Elective Surgical Procedures / Q000009:adverse effects; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects*; D005260:Female; D006397:Hematinics / Q000009:adverse effects; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D019990:Perioperative Care / Q000009:adverse effects*; D011446:Prospective Studies; D011994:Recombinant Proteins; D013131:Spine / Q000601:surgery; D018615:Ultrasonography, Doppler, Color; D020246:Venous Thrombosis / Q000139:chemically induced* / Q000000981:diagnostic imaging
chemical_list: D000925:Anticoagulants; D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa