Evaluation of Venous Thromboembolism Prevention in High-Risk Trauma Patients

Phase 4

Completed

Brief Summary: This is a pilot study to determine if anti-thrombin III (AT-III) serum concentrations differ between patients with normal versus subtherapeutic anti-Xa trough concentrations when placed on enoxaparin 30 mg twice daily for VTE prophylaxis. Secondarily, this study will compare two enoxaparin dosing strategies.

Detailed Description: This is a pilot study to determine if AT-III serum concentrations differ between patients with normal (\>= 0.1 IU/mL) versus subtherapeutic (\<0.1 IU/mL) anti-Xa trough concentrations when placed on enoxaparin 30 mg twice daily for venous thromboembolism (VTE) prophylaxis. Secondarily, this study will compare two enoxaparin dosing strategies: standard 30 mg twice daily and a dosing strategy based on trough anti-Xa values in high-risk trauma patients.

Specific aims include: 1) to compare the extent of reduced AT-III activity between patients with trough anti-Xa \>= 0.1 IU/mL and \< 0.1 IU/mL upon initial assay; 2) to determine the proportion of patients who reach goal anti-Xa and the time to goal anti-Xa achievement between two interventional dosing strategies: enoxaparin 40 mg every 12 hours (with consideration to increase to 50 mg every 12 hours if recheck anti-Xa is not at goal) and enoxaparin 30 mg every eight hours; 3) to compare anti-Xa enoxaparin dosing strategies based on VTE, bleeding rates, transfusion requirements, drug discontinuation rate and bioaccumulation, and 4) to determine patient-specific factors that correlate to subtherapeutic anti-Xa such as serial AT-III activity, weight, body mass index, age, cumulative fluid administration, and thromboelastography (TEG).

Recruitment & Eligibility

Inclusion Criteria

Multi-system trauma
Anticipated length of stay of at least 72 hours
At high risk (risk adjustment profile [RAP] >= 5) and initiated on enoxaparin 30 mg every 12 hours per VTE prophylaxis protocol
No counterindication to trauma team VTE prophylaxis protocol (e.g., intracranial bleeding, incomplete spinal cord injury with hematoma within 24 hours post injury, ongoing hemorrhage, uncorrected coagulopathy, >= grade IV liver or spleen injury, intraocular injury)

Exclusion Criteria

Renal dysfunction (creatinine clearance < 30 mL/min or on continuous renal replacement therapy)
Weight < 50 kg or > 150 kg
Platelet count < 50,000
Allergy to heparin or low molecular weight heparin
On therapeutic anticoagulation on admission or requiring it within 24 hours of admission
Isolated intracranial hemorrhage
Known hyperbilirubinemia (serum bilirubin > 6.6 mg/dL)
Pregnancy
Incarceration

Arm && Interventions

Group	Intervention	Description
Anti-Xa <0.1 IU/mL:enoxaparin 40 mg q12h	Enoxaparin 40 mg q12h	Patients with serum anti-Xa level \< 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours who then receive enoxaparin 40 mg every 12 hours. If repeat steady state trough anti-Xa is subtherapeutic, dose will be increased to enoxaparin 50 mg every 12 hours.
Anti-Xa <0.1 IU/mL:enoxaparin 30 mg q8h	Enoxaparin 30 mg q8h	Patients with serum anti-Xa level \< 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours who then receive enoxaparin 30 mg every eight hours

Primary Outcome Measures

Name	Time	Method
Initial AT-III Activity -- Control Group vs. Intervention Group Prior to Randomization	After third dose of enoxaparin 30mg q12h, which will typically be on Day 2 of enoxaparin	Serum AT-III (% activity) will be compared between the control group and the intervention group patients (combined) after the third dose of enoxaparin 30 mg every 12 hours once initiated at the discretion of the trauma service per current VTE prophylaxis protocol

Secondary Outcome Measures