Minimization of bleeding related adverse drug events in plastic & reconstructive surgery patients randomized to different postoperative anticoagulant regimens

Principal Investigator: CHRISTOPHER  PANNUCCI
Keywords: Enoxaparin , Deep venous thrombosis , Pulmonary embolus , Venous thromboembolism , Metabolism Department: Plastic & Reconstruct Surgery
IRB Number: 00100416 Co Investigator:  
Specialty: Plastic Surgery, Plastic Surgery, Plastic Surgery, Plastic Surgery, Plastic Surgery, Plastic Surgery, Plastic Surgery, Plastic Surgery, Plastic Surgery, Plastic Surgery
Sub Specialties: Plastic Surgery, Cosmetic, Head and Neck Reconstruction, Microsurgery, Breast Surgery, Plastic Surgery, Hand Upper Extremity and Microvascular Surgery, Plastic Surgery, Facial, Trunk and Extremity Reconstruction, Flap Surgery, Wound Healing
Recruitment Status: Recruiting

Contact Information

CHRISTOPHER  PANNUCCI
christopher.pannucci@hsc.utah.edu
801 581 7719

Brief Summary

Venous thromboembolism (VTE) is the proximate cause of 250,000 hospitalizations annually in the United States.  Pulmonary embolus (PE) is implicated in over 100,000 deaths each year, and one third of VTE-associated deaths occur after surgical procedures.  Surgical patients are among those at highest risk for VTE events and post-operative anticoagulation medications, known as chemical prophylaxis, are known to significantly decrease VTE risk.  However, surgeons often provide sub-optimal doses of chemical prophylaxis, delay chemical prophylaxis initiation, or avoid chemical prophylaxis altogether due to concern for adverse drug events (ADE), most notably post-operative bleeding. Surgeon’s behavior is not entirely unjustified.  Bleeding from chemical prophylaxis is an ADE than can require return to the operating room, need for transfusion, or death.  Bleeding ADEs are an important cause of morbidity or mortality for patients.  However, surgeons must balance bleeding ADEs with the risk for VTE, which is in its own right a life or limb-threatening event.   

 

Plastic and reconstructive surgeons consistently create large, raw surfaces as part of their operative procedures.  Thus, plastic and reconstructive surgery patients are among those at highest risk for chemical prophylaxis-associated bleeding ADEs.  Our preliminary data has shown that a fixed, or “one size fits all” dose of enoxaparin, an anticoagulant, can allow a high proportion of patients to have appropriately thinned blood, measured by anti-Factor Xa (aFXa) levels.  Patients with adequate aFXa levels are known to have significantly decreased VTE risk, which is desirable.  However, 30% of patients who receive fixed dose enoxaparin have blood that is too thin, and patients who are over-anticoagulated are significantly more likely to have ADEs including bleeding requiring return to the operating room, need for blood transfusion, or even death.  The optimal way to dose enoxaparin to minimize ADEs remains unknown.  This study seeks to optimize both the safety and effectiveness of enoxaparin chemical prophylaxis by comparing aFXa levels, bleeding events, and VTE events among plastic and reconstructive surgery patients randomized to receive two different enoxaparin dose regimens. 

AIMS

Aim 1: To examine aFXa levels as a marker of bleeding ADEs in plastic & reconstructive surgery patients randomized to enoxaparin 40mg twice daily versus 0.5mg/kg twice daily.

Rationale: Our preliminary data demonstrate that 30% of patients are over-anticoagulated with enoxaparin 40mg twice daily, and that enoxaparin 0.5mg/kg twice daily may be more appropriate for most patients.

Hypothesis: Patients randomized to enoxaparin 0.5mg/kg twice daily, when compared to 40mg twice daily, will be significantly less likely to be over-anticoagulated (aFXa >0.4 IU/mL). 

 

Aim 2: To examine aFXa levels as a marker of VTE prevention in plastic & reconstructive surgery patients randomized to enoxaparin 40mg twice daily versus 0.5mg/kg twice daily.

Rationale: Inadequate anticoagulation is known to significantly increase VTE risk.  Alterations in enoxaparin dose must consider risk for bleeding ADEs and VTE risk reduction.

Hypothesis: For the risk of under-anticoagulation (aFXa <0.2 IU/mL), enoxaparin 0.5mg/kg twice daily will not be inferior to enoxaparin 40mg twice daily.

 

Aim 3: To examine 1) risk for 90-day bleeding ADEs and 2) risk for symptomatic 90-day VTE in plastic & reconstructive surgery patients randomized to enoxaparin 40mg twice daily versus 0.5mg/kg twice daily.

Rationale: Surgeons must balance bleeding ADEs and VTE risk when making decisions about chemical prophylaxis regimen.    

Hypothesis:  The proposed work will provide descriptive data on rates of clinically relevant bleeding ADEs and symptomatic VTE.  The proposed work will identify a very large difference in bleeding ADEs or VTE risk in patients randomized to two different enoxaparin dosing regimens, if present.

Inclusion Criteria

We will identify plastic & reconstructive surgery patients scheduled for post-operative admission.  Patients will be approached in the preoperative area by the research coordinator.  Informed consent for randomization and study participation will be obtained.  Inclusion criteria will include adult (age≥18) patients who have plastic & reconstructive surgery under general anesthesia.  Expected post-operative stay will be ≥2 days to allow for peak and trough aFXa levels to be drawn after the third dose.  Patients who meet inclusion criteria and provide informed consent will subsequently be randomized.

Exclusion Criteria

Exclusion criteria will include contraindication to use of enoxaparin, intracranial bleeding/stroke, hematoma or bleeding disorder, heparin-induced thrombocytopenia positive, creatinine clearance ≤ 30mL/min, serum creatinine >1.6mg/dL, epidural anesthesia, or patients placed on non-enoxaparin chemoprophylaxis regimens per their surgeon’s discretion.  Patients whose gross weight exceeds 150kg will be excluded from the study (see below).