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

Singer, Jonathan P.; Huang, Meng-Yu; Hui, Christine; Blanc, Paul D.; Boettger, Rebecca F.; Golden, Jeffery; Watkins, Katherine; Hoopes, Charles; Leard, Lorriana E.

doi:10.1016/j.healun.2010.04.018

« Previous Next »The Journal of Heart and Lung Transplantation
Volume 29, Issue 9 , Pages 1009-1013, September 2010

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

Jonathan P. Singer, MD, MS
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California
- Reprint requests: Jonathan P. Singer, MD, MS, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, Box 0111, M1097, 505 Parnassus Avenue, San Francisco, CA 94143. Telephone: 415-476-6030. Fax: 415-476-5712
Meng-Yu Huang, PharmD
- Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, California
Christine Hui, PharmD
- Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, California
Paul D. Blanc, MD, MPH
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California
Rebecca F. Boettger, PharmD
- Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, California
Jeffery Golden, MD
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California
Katherine Watkins, PharmD
- Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, California
Charles Hoopes, MD
- Division of Cardiothoracic Surgery, Department of Surgery, University of California, San Francisco, San Francisco, California
Lorriana E. Leard, MD
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California

published online 07 June 2010.

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 r² = 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.

Keywords: lung transplantation, venous thromboembolism, anticoagulation, enoxaparin, deep venous thrombosis, pulmonary embolism