Fixed Versus Weight-Based Enoxaparin Dosing in Thoracic Surgery Patients

VTE encompasses deep venous thrombosis and pulmonary embolus and is the proximate cause of
death in over 100,000 hospitalized patients per year 4,5. To put this in better context, VTE
kills more people each year than the annual morbidity from motor vehicle crashes and breast
cancer combined—and one third of these deaths are known to occur after surgical procedures
34. "Breakthrough" VTE events occur in patients despite the receipt of guideline-compliant
chemical prophylaxis. These events can be frustrating for surgeons, can represent a resource
and financial burden for hospital systems, and most importantly, can be life or limb
threatening for patients.

Existing data from our group and others suggests that inadequate enoxaparin dosing,
quantified by aFXa levels, represents a plausible explanatory mechanism for "breakthrough"
VTE events that occur among thoracic surgery patients. This project will examine the
pharmacodynamics of fixed dose enoxaparin (40mg/day) after VATS—this dose and frequency were
the most commonly prescribed VTE chemical prophylaxis strategy in a recent survey of thoracic
surgeons 35. If inadequate aFXa levels are observed with fixed enoxaparin dosing, the study
will design, implement and test a weight-based dosing approach to optimize aFXa levels. The
study will also examine how alteration of enoxaparin dose magnitude affects peak aFXa levels
and risk for VTE and major bleeding events.

Aim 1: To evaluate peak steady-state aFXa levels in response to a fixed dose of enoxaparin
prophylaxis (40mg once daily) in VATS patients.

Rationale: Over 12% of thoracic surgery patients have "breakthrough" VTE events despite
receipt of fixed dose chemical prophylaxis 29. Fixed dose enoxaparin prophylaxis has been
shown to be inadequate for the majority of patients in other surgical subspecialties.

Hypothesis: Peak steady state aFXa levels will be within the accepted range (0.3-0.5 IU/mL)
in 40% of patients after VATS.

Aim 2: To compare the effect of fixed (40mg once daily) and weight-based (0.5mg/kg once
daily) enoxaparin prophylaxis on peak steady state aFXa levels after VATS.

Rationale: Our preliminary data shows a potential association between body weight and aFXa
levels in response to fixed dosing; this will be confirmed using a multi-center approach in
Aim #1. Body weight may be an important predictor of appropriate enoxaparin dose.

Hypothesis: Weight-based enoxaparin prophylaxis, when compared to fixed dose prophylaxis,
will increase the proportion of patients with in-range peak aFXa levels from 40% to 80%.

Aim 3: To examine rates of 90-day VTE and clinically relevant bleeding events in VATS
patients who receive fixed dose vs. weight-based enoxaparin prophylaxis.

Rationale: This observational Aim will allow us to better understand VTE and bleeding rates
after VATS. Since these are rare events it is impossible to power the study to detect
increases or decreases in risk between the dose groups. This study does provide a way to
demonstrate an unexpected, very large difference in risk.

Hypothesis: Rates of post-operative VTE and clinically relevant bleeding will be less than 2%
in each group.

Inclusion Criteria:

- receiving Video-Assisted Thoracoscopic Surgery

- able to have Enoxaparin initiated within 8 hours after procedure

Exclusion Criteria:

- Contraindication to use of enoxaparin

- Intracranial bleeding/stroke

- Hematoma or bleeding disorder

- Heparin-induced thrombocytopenia positive

- Creatinine clearance less than or equal to 30 mL/min

- Serum creatinine greater than 1.6 mg/dL

- Epidural catheter