Supratherapeutic anticoagulation from low-molecular-weight heparin in lung transplant recipients.
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.
Singer
Jonathan P
JP
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA. jon.singer@ucsf.edu
Huang
Meng-Yu
MY
Hui
Christine
C
Blanc
Paul D
PD
Boettger
Rebecca F
RF
Golden
Jeffery
J
Watkins
Katherine
K
Hoopes
Charles
C
Leard
Lorriana E
LE
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
D000925:Anticoagulants; D017984:Enoxaparin; D006495:Heparin, Low-Molecular-Weight; D007166:Immunosuppressive Agents; D003404:Creatinine; D015951:Factor Xa