title: Supratherapeutic anticoagulation from low-molecular-weight heparin in lung transplant recipients.
abstract: BACKGROUND
  Venous thromboembolism (VTE) is common after lung transplantation. Enoxaparin is an approved therapy for VTE and anti-factor Xa level can be used to monitor enoxaparin activity. Some studies have demonstrated elevated anti-factor Xa levels are associated with an increased risk of hemorrhage. Having identified a high incidence of supratherapeutic anti-factor Xa levels in lung transplant recipients, we aimed to elucidate the relationship between enoxaparin dose and anti-factor Xa level in this patient population.
  
  
  METHODS
  We identified post-lung transplantation patients with VTE receiving therapeutic enoxaparin who had anti-factor Xa level measured. Standard enoxaparin dosing was defined as 0.9 to 1.1 mg/kg. After identifying a high incidence of supratherapeutic anti-factor Xa levels, we implemented "non-standard" dosing of 0.8 mg/kg. Multivariate linear regression analysis was used to examine the association between enoxaparin dose and anti-factor Xa level; age, body mass index (BMI) and creatinine clearance were included as covariates.
  
  
  RESULTS
  In the cohort, 18 patients received standard and 8 patients received non-standard enoxaparin dosing. Twelve of 18 patients (67%; 95% confidence interval [CI]: 43% to 91%) receiving standard dosing had supratherapeutic anti-factor Xa levels vs 0 of 8 patients (0%; 95% CI: 0% to 37%) receiving lower non-standard dosing (p = 0.002). Anti-factor Xa levels were significantly different between the two groups; the mean anti-factor Xa level was 1.3 IU/ml (95% CI: 1.06 to 1.53) in the standard group vs 0.79 IU/ml (95% CI: 0.67 to 0.91) in the non-standard group (p = 0.008). After controlling for covariates, for each 0.1-mg/kg increase in enoxaparin, the mean anti-factor Xa level increased by 0.18 IU/ml (95% CI: 0.05 to 0.31; p = 0.011; model r(2) = 0.53).
  
  
  CONCLUSIONS
  Standard dosing of enoxaparin in lung transplant recipients is associated with a high incidence of supratherapeutic anti-Xa levels. Further study will be required to correlate this finding with risk of hemorrhage.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA. jon.singer@ucsf.edu
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Singer
authors.forename: Meng-Yu
authors.initials: MY
authors.lastname: Huang
authors.forename: Christine
authors.initials: C
authors.lastname: Hui
authors.forename: Paul D
authors.initials: PD
authors.lastname: Blanc
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Boettger
authors.forename: Jeffery
authors.initials: J
authors.lastname: Golden
authors.forename: Katherine
authors.initials: K
authors.lastname: Watkins
authors.forename: Charles
authors.initials: C
authors.lastname: Hoopes
authors.forename: Lorriana E
authors.initials: LE
authors.lastname: Leard
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D003404:Creatinine / Q000378:metabolism; D017984:Enoxaparin / Q000627:therapeutic use; D015951:Factor Xa / Q000032:analysis / Q000276:immunology; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016040:Lung Transplantation / Q000009:adverse effects / Q000276:immunology / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000175:diagnosis; D011517:Prothrombin Time; D011655:Pulmonary Embolism / Q000175:diagnosis; D014463:Ultrasonography; D020246:Venous Thrombosis / Q000000981:diagnostic imaging
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D006495:Heparin, Low-Molecular-Weight; D007166:Immunosuppressive Agents; D003404:Creatinine; D015951:Factor Xa