Fixed versus Weight-Based Enoxaparin Dosing in Thoracic Surgery Patients

Principal Investigator: CHRISTOPHER  PANNUCCI
Keywords: Enoxaparin , Metabolism , Plastic Surgery , Clot , Embolism , Anti-factor Xa Department: Plastic & Reconstruct Surgery
IRB Number: 00100484 Co Investigator:  
Specialty: Plastic Surgery
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Kory Fleming
kory.fleming@hsc.utah.edu
8015816501

Brief Summary

HYPOTHESIS / AIMS

Venous thromboembolism (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 correlation between gross 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.  As events are expected to be rare, we recognize that the proposed study is underpowered to rigorously examine alterations in VTE or bleeding rates in response to enoxaparin dose escalation.

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

Inclusion Criteria

We will include adult patients who have VATS surgery and can have enoxaparin initiated within 8 hours after procedure.  All patients will undergo informed consent.

Exclusion Criteria

We will exclude those with intracranial bleeding/stroke, bleeding disorder, heparin-induced thrombocytopenia, creatinine clearance ≤ 30mL/min, epidural catheter, or serum creatinine >1.6mg/dL.