Enoxaparin Metabolism in Reconstructive Surgery Patients

Venous thromboembolism (VTE) is a leading cause of death among hospitalized patients, and is
an important patient safety issue in plastic surgery. Previous work has shown that enoxaparin
prophylaxis can prevent many post-operative VTE events, and current American Society of
Plastic Surgeons guidelines support enoxaparin prophylaxis for high-risk patients. However,
the Plastic Surgery Foundation-funded Venous Thromboembolism Prevention Study showed that 1
in 25 highest risk patients still had a "breakthrough" VTE event despite receipt of
guideline-compliant enoxaparin prophylaxis. Highest risk patients often have cancer or trauma
reconstruction. These surgeries may have surgical injury that is equal in scope to patients
with traumatic or thermal injury. Previous work in patients with traumatic or thermal injury
has shown that enoxaparin metabolism, measured by anti-factor Xa (aFXa) level, is
substantially increased: a higher degree of injury is associated with higher enoxaparin dose
requirements to achieve prophylactic levels. "Breakthrough" VTE events may occur in plastic
and reconstructive surgery patients due to inadequate enoxaparin dosing. The investigators
will examine enoxaparin pharmacokinetics and test whether a clinical protocol for real-time
enoxaparin dose adjustment can favorably alter the proportion of patients with in-range aFXa
levels. Primary outcomes include 1) peak and trough steady-state aFXa levels in response to
standard and escalated doses of enoxaparin and 2) the proportion of patients with appropriate
aFXa levels pre and post initiation of a clinical protocol for enoxaparin dose adjustment.
The investigators expect that standard dosing will result in inadequate aFXa peak and trough
levels, and that the clinical dose adjustment protocol will significantly improve the
proportion of in-range aFXa levels. The investigators will also develop a linear
regression-based equation to calculate, based on patient-level factors, the required dose of
enoxaparin to generate in-range aFXa levels. This research may show that the current "one
size fits all" approach to enoxaparin prophylaxis is insufficient. In the trauma and
orthopaedic populations, patients with low initial aFXa levels are significantly more likely
to develop deep venous thrombosis. Thus, this study has important implications for
appropriate enoxaparin dose magnitude and frequency, and may ultimately help to decrease the
substantial morbidity and mortality associated with post-operative VTE.

Inclusion Criteria:

Inclusion criteria will include:

- adult (age ≥18) patients presenting for reconstructive surgery under general
anesthesia.

- expected post-operative stay will be at least three days to allow peak aFXa levels to
be drawn.

- eligible patients will include those having major reconstructive surgery.

Exclusion Criteria:

Exclusion criteria will include:

- contraindication to use of enoxaparin,

- intracranial bleeding/stroke,

- hematoma or bleeding disorder,

- known heparin-induced thrombocytopenia,

- creatinine clearance ≤30mL/min,

- serum creatinine >1.6mg/dL, or epidural anesthesia.