title: Evaluation of Enoxaparin Dosing as a Risk Factor for Bleeding in Lung Transplant Recipients.
abstract: Lung transplant recipients commonly develop complications that lead to anticoagulation. Standard FDA-approved enoxaparin dosing in this population results in a high incidence of above-goal anti-Xa levels, but its association with bleeding remains unclear.
  
  
  
  To evaluate the association between enoxaparin dosing and bleeding in lung transplant recipients and assess the relationship between dosing and anti-Xa levels.
  
  
  
  We conducted a single-center retrospective cohort study of adult lung transplant recipients who received therapeutic enoxaparin between 2000 and 2012 at a tertiary academic center. We dichotomized enoxaparin dosing regimens into standard dose (FDA-approved doses with a 10% rounding margin) and reduced dose. Clinicians ordered anti-Xa levels as deemed clinically appropriate. The primary outcome was major bleeding or clinically relevant nonmajor bleeding.
  
  
  
  Of 222 patients treated with enoxaparin, 33 (14.9%) had bleeding events, of which half (17/33) were major. Bleeding occurred in 25/146 (17.1%) patients who received standard-dose enoxaparin versus 8/76 (10.5%) patients who received reduced-dose enoxaparin (P = 0.190). Multiple logistic regression demonstrated an independent association between standard-dose enoxaparin and bleeding, after adjusting for confounders (adjusted odds ratio = 3.04; 95% CI = 1.14-8.10). The median enoxaparin dose in patients with above-goal versus at-goal anti-Xa levels was 0.89 versus 0.76 mg/kg every 12 hours; P = 0.006. However, doses yielding at-goal anti-Xa levels had an interquartile range of 0.67 to 0.90 mg/kg, which overlapped with doses yielding above- and below-goal anti-Xa levels.
  
  
  
  Enoxaparin dose reduction and anti-Xa level monitoring can improve drug safety and facilitate individualized dose optimization in lung transplant recipients.
authors.affiliation: Barnes-Jewish Hospital, St Louis, MO, USA University of Houston College of Pharmacy, Houston, TX, USA aksofjan@uh.edu.
authors.forename: Amelia K
authors.initials: AK
authors.lastname: Sofjan
authors.affiliation: Barnes-Jewish Hospital, St Louis, MO, USA University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Iuppa
authors.affiliation: Barnes-Jewish Hospital, St Louis, MO, USA.
authors.forename: K Bennett
authors.initials: KB
authors.lastname: Bain
authors.affiliation: Barnes-Jewish Hospital, St Louis, MO, USA.
authors.forename: Eli N
authors.initials: EN
authors.lastname: Deal
authors.affiliation: Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Witt
authors.affiliation: Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Ramsey R
authors.initials: RR
authors.lastname: Hachem
authors.affiliation: Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Yusen
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D002985:Clinical Protocols; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015951:Factor Xa / Q000032:analysis; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D012189:Retrospective Studies; D012307:Risk Factors; D066027:Transplant Recipients
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D015951:Factor Xa
keywords: anticoagulants; drug monitoring; enoxaparin; factor Xa; hemorrhage; heparin; low molecular weight; lung transplantation; postoperative complications