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

J Heart Lung Transplant. 2010 Sep;29(9):1009-13. doi: 10.1016/j.healun.2010.04.018. Epub 2010 Jun 8.

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.

MeSH terms

  • Adult
  • Aged
  • Anticoagulants / therapeutic use*
  • Creatinine / metabolism
  • Enoxaparin / therapeutic use
  • Factor Xa / analysis
  • Factor Xa / immunology
  • Female
  • Heparin, Low-Molecular-Weight / therapeutic use*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Lung Transplantation / adverse effects
  • Lung Transplantation / immunology
  • Lung Transplantation / methods*
  • Male
  • Middle Aged
  • Postoperative Complications / diagnosis
  • Prothrombin Time
  • Pulmonary Embolism / diagnosis
  • Ultrasonography
  • Venous Thrombosis / diagnostic imaging

Substances

  • Anticoagulants
  • Enoxaparin
  • Heparin, Low-Molecular-Weight
  • Immunosuppressive Agents
  • Creatinine
  • Factor Xa