title: Standard prophylactic enoxaparin dosing leads to inadequate anti-Xa levels and increased deep venous thrombosis rates in critically ill trauma and surgical patients.
abstract: BACKGROUND
  Deep venous thromboses (DVT) continue to cause significant morbidity in critically ill patients. Standard prophylaxis for high risk patients includes twice-daily dosing with 30 mg enoxaparin. Despite prophylaxis, DVT rates still exceed 10% to 15%. Anti-Xa levels are used to measure the activity of enoxaparin and 12-hour trough levels <or=0.1 IU/mL have been associated with higher rates of DVT in orthopedic patients. We hypothesized that low Anti-Xa levels would be found in critically ill trauma and surgical patients and that low levels would be associated with higher rates of DVT.
  
  
  METHODS
  All patients on the surgical intensive care unit (ICU) service were prospectively followed. In the absence of contraindications, patients were given prophylactic enoxaparin and anti-Xa levels were drawn after the third dose. Trough levels <or=0.1 IU/mL were considered low. Screening duplex exams were obtained within 48 hours of admission and then weekly. Patients were excluded if they did not receive a duplex, if they had a prior DVT, or if they lacked correctly timed anti-Xa levels. DVT rates and demographic data were compared between patients with low and normal anti-Xa levels.
  
  
  RESULTS
  Data were complete for 54 patients. Eighty-five percent suffered trauma (Injury Severity Score of 25 +/- 12) and 74% were male. Overall, 27 patients (50%) had low anti-Xa levels. Patients with low anti-Xa levels had significantly more DVTs than those with normal levels (37% vs. 11%, p = 0.026), despite similar age, body mass index, Injury Severity Score, creatinine clearance, high risk injuries, and ICU/ventilator days.
  
  
  CONCLUSIONS
  Standard dosing of enoxaparin leads to low anti-Xa levels in half of surgical ICU patients. Low levels are associated with a significant increase in the risk of DVT. These data support future studies using adjusted-dose enoxaparin.
authors.affiliation: Department of Surgery, University of California, Irvine Medical Center, Orange, California 92868, USA. malinosd@uci.edu
authors.forename: Darren
authors.initials: D
authors.lastname: Malinoski
authors.forename: Fariba
authors.initials: F
authors.lastname: Jafari
authors.forename: Tyler
authors.initials: T
authors.lastname: Ewing
authors.forename: Chris
authors.initials: C
authors.lastname: Ardary
authors.forename: Heather
authors.initials: H
authors.lastname: Conniff
authors.forename: Mark
authors.initials: M
authors.lastname: Baje
authors.forename: Allen
authors.initials: A
authors.lastname: Kong
authors.forename: Michael E
authors.initials: ME
authors.lastname: Lekawa
authors.forename: Matthew O
authors.initials: MO
authors.lastname: Dolich
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Cinat
authors.forename: Cristobal
authors.initials: C
authors.lastname: Barrios
authors.forename: David B
authors.initials: DB
authors.lastname: Hoyt
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D017984:Enoxaparin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D015951:Factor Xa / Q000378:metabolism*; D005260:Female; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D018616:Ultrasonography, Doppler, Duplex; D020246:Venous Thrombosis / Q000000981:diagnostic imaging / Q000517:prevention & control*; D014947:Wounds and Injuries / Q000097:blood / Q000150:complications / Q000601:surgery
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D015951:Factor Xa