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Supratherapeutic anticoagulation from low-molecular-weight heparin in lung transplant recipients.

AbstractBACKGROUND:
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.
AuthorsJonathan P Singer, Meng-Yu Huang, Christine Hui, Paul D Blanc, Rebecca F Boettger, Jeffery Golden, Katherine Watkins, Charles Hoopes, Lorriana E Leard
JournalThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 29 Issue 9 Pg. 1009-13 (Sep 2010) ISSN: 1557-3117 [Electronic] United States
PMID20627627 (Publication Type: Journal Article)
CopyrightCopyright 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Anticoagulants
  • Enoxaparin
  • Heparin, Low-Molecular-Weight
  • Immunosuppressive Agents
  • Creatinine
  • Factor Xa
Topics
  • Adult
  • Aged
  • Anticoagulants (therapeutic use)
  • Creatinine (metabolism)
  • Enoxaparin (therapeutic use)
  • Factor Xa (analysis, immunology)
  • Female
  • Heparin, Low-Molecular-Weight (therapeutic use)
  • Humans
  • Immunosuppressive Agents (therapeutic use)
  • Lung Transplantation (adverse effects, immunology, methods)
  • Male
  • Middle Aged
  • Postoperative Complications (diagnosis)
  • Prothrombin Time
  • Pulmonary Embolism (diagnosis)
  • Ultrasonography
  • Venous Thrombosis (diagnostic imaging)

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