Fixed-Dose Enoxaparin Prophylaxis Is Inadequate for the Majority of Surgical Patients and Inadequate Dosing Predicts Postoperative Venous Thromboembolism

“Breakthrough” venous thromboembolism (VTE) events, or events that occur despite receipt of chemical prophylaxis, remain an enigma for surgeons. The goal of this study was to evaluate the degree of anticoagulation achieved with standard doses of enoxaparin prophylaxis using anti-factor Xa (aFXa) levels and to examine the relationship between aFXa and downstream 90-day VTE events. Goal peak aFXa was 0.2 to 0.4 IU/mL for patients who received twice-daily prophylaxis and 0.3 to 0.5 IU/mL for patients who received once-daily prophylaxis; these ranges have been shown to maximize VTE risk reduction while reducing risk for clinically relevant bleeding. Scatter plot analysis examined the relationship between patients’ weight and peak aFXa in response to fixed doses, and time series (Kaplan-Meier) analysis examined the relationship between low aFXa and 90-day VTE events. Data for 432 surgical patients were available for analysis; all patients were recruited prospectively into one of six clinical trials at our institution. This included 283 (65.5%) patients who received twice-daily prophylaxis and 149 (34.5%) who received once-daily prophylaxis. Primary surgical procedure type included plastic and reconstructive surgery (48.6%), orthopedic surgery (25.2%), trauma surgery (12.7%), colorectal surgery (6.5%), and thoracic surgery (6.9%); 52% of patients (n = 224) had inadequate aFXa levels in response to fixed-dose prophylaxis. Patients’ weight was associated with peak aFXa (Fig 1). Most important, patients with low aFXa, indicative of inadequate enoxaparin prophylaxis, were significantly more likely to have 90-day VTE than those patients whose aFXa was adequate (6.3% vs 1.9%; log-rank, P = .029; Fig 2). A “one size fits all” strategy for enoxaparin prophylaxis is inadequate for the majority of patients, and the patient’s weight can be used to predict rapidity of enoxaparin metabolism. Patients whose enoxaparin prophylaxis is inadequate are significantly more likely to have 90-day VTE events.Fig 2Relationship between low anti-factor Xa (aFXa) and 90-day venous thromboembolism (VTE).View Large Image Figure ViewerDownload Hi-res image Download (PPT)