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Original Investigation
November 2016

Association Between Enoxaparin Dosage Adjusted by Anti–Factor Xa Trough Level and Clinically Evident Venous Thromboembolism After Trauma

Author Affiliations
  • 1Department of Surgery, Division of Trauma and Critical Care, Cedars-Sinai Medical Center, Los Angeles, California
JAMA Surg. 2016;151(11):1006-1013. doi:10.1001/jamasurg.2016.1662
Key Points

Question  Will adjusting the dosage of enoxaparin by prophylactic anti–factor Xa (anti-Xa) trough levels reduce the venous thromboembolism rate in trauma patients?

Findings  In this cohort study of 205 trauma patients, those who received enoxaparin adjusted by anti-Xa trough level were compared with those who received enoxaparin sodium at a dosage of 30 mg twice daily without adjustment. Incidence of venous thromboembolism was significantly lower in those whose enoxaparin was adjusted by anti-Xa trough levels.

Meaning  Enoxaparin dosage adjustment may lead to a reduced rate of venous thromboembolism without an increased risk of bleeding.


Importance  Trauma patients are at high risk for developing venous thromboembolism (VTE). The VTE rate when enoxaparin sodium is dosed by anti–factor Xa (anti-Xa) trough level is not well described.

Objective  To determine whether targeting a prophylactic anti-Xa trough level by adjusting the enoxaparin dose would reduce the VTE rate in trauma patients.

Design, Setting, and Participants  Single-institution, historic vs prospective cohort comparison study at an urban, academic, level I trauma center. The prospective cohort was enrolled from August 2014 to May 2015 and compared with a historic cohort admitted from August 2013 to May 2014. Trauma patients who received enoxaparin adjusted by anti-Xa trough level (adjustment group) were compared with those who received enoxaparin sodium at a dosage of 30 mg twice daily (control group). Patients were excluded if they were younger than 18 years, had a length of hospital stay less than 2 days, or had preexisting deep vein thrombosis. Patients were excluded from the adjustment group for changes in the choice of thromboprophylaxis (heparin, enoxaparin once-daily dosing, early ambulation), hospital discharge before initial trough levels could be drawn, or incorrect timing of trough levels.

Exposures  Anti-Xa trough levels were monitored in patients in the adjustment group receiving 3 or more consecutive doses of enoxaparin sodium, 30 mg twice daily. Patients with a trough level of 0.1 IU/mL or lower received enoxaparin sodium increased by 10-mg increments. After providing 3 adjusted doses of enoxaparin, the trough level was redrawn and the dosage was adjusted as necessary. Patients in the control group received enoxaparin sodium at a dosage of 30 mg twice daily without adjustments.

Main Outcomes and Measures  Rates of symptomatic VTE (deep vein thrombosis and pulmonary embolism, confirmed by duplex ultrasonography and chest computed tomographic angiography, respectively) and bleeding risk.

Results  A total of 205 patients (mean [SD] age, 41.3 [18.2] years; 75.1% male) were studied, 87 in the adjustment group and 118 in the control group, with similar baseline characteristics and injury profiles. Subprophylactic anti-Xa troughs were noted in 73 of 87 patients (83.9%) in the adjustment group, and the majority of patients (57 of 87 patients [65.5%]) required dosage adjustment of enoxaparin sodium to 40 mg twice daily. Incidence of VTE was significantly lower in the adjustment group than in the control group (1.1% vs 7.6%, respectively; P = .046). When the adjustment group was compared with the control group, no significant difference was noted in the rate of packed red blood cell transfusion (6.9% vs 12.7%, respectively; P = .18) or mean (SD) hematocrit at discharge (34.5% [6.3%] vs 33.4% [6.8%], respectively [to convert to proportion of 1.0, multiply by 0.01]; P = .19).

Conclusions and Relevance  In this study, subprophylactic anti-Xa trough levels were common in trauma patients. Enoxaparin dosage adjustment may lead to a reduced rate of VTE without an increased risk of bleeding.