Low Anti-Factor Xa Level Predicts 90-Day Symptomatic Venous Thromboembolism in Surgical Patients Receiving Enoxaparin Prophylaxis: A Pooled Analysis of Eight Clinical Trials.

OBJECTIVE: To examine the relationship between enoxaparin dose adequacy, quantified with anti-Factor Xa (aFXa) levels, and 90-day symptomatic venous thromboembolism (VTE) and postoperative bleeding. SUMMARY BACKGROUND DATA: Surgical patients often develop "breakthrough" VTE events-those which occur despite receiving chemical anticoagulation. We hypothesize that surgical patients with low aFXa levels will be more likely to develop 90-day VTE, and those with high aFXa will be more likely to bleed. METHODS: Pooled analysis of eight clinical trials (N = 985) from a single institution over a 4 year period. Patients had peak steady state aFXa levels in response to a known initial enoxaparin dose, and were followed for 90 days. Survival analysis log-rank test examined associations between aFXa level category and 90-day symptomatic VTE and bleeding. RESULTS: Among 985 patients, 2.3% (n = 23) had symptomatic 90-day VTE, 4.2% (n = 41) had 90-day clinically relevant bleeding, and 2.1% (n = 21) had major bleeding. Patients with initial low aFXa were significantly more likely to have 90-day VTE than patients with adequate or high aFXa (4.2% vs 1.3%, P = 0.007). In a stratified analysis, this relationship was significant for patients who received twice daily (6.2% vs 1.5%, P = 0.003), but not once daily (3.0% vs 0.7%, P = 0.10) enoxaparin. No association was seen between high aFXa and 90-day clinically relevant bleeding (4.8% vs 2.9%, P = 0.34) or major bleeding (3.6% vs 1.6%, P = 0.18). CONCLUSIONS: This manuscript establishes inadequate enoxaparin dosing as a plausible mechanism for breakthrough VTE in surgical patients, and identifies anticoagulant dose adequacy as a novel target for process improvement measures.

Optimal Dosing of Prophylactic Enoxaparin after Surgical Procedures: Results of the Double-Blind, Randomized, Controlled FIxed or Variable Enoxaparin (FIVE) Trial.

BACKGROUND: The accepted "one-size-fits-all" dose strategy for prophylactic enoxaparin may not optimize the medication's risks and benefits after surgical procedures. The authors hypothesized that weight-based administration might improve the pharmacokinetics of prophylactic enoxaparin when compared to fixed-dose administration. METHODS: The FIxed or Variable Enoxaparin (FIVE) trial was a randomized, double-blind trial that compared the pharmacokinetic and clinical outcomes of patients assigned randomly to postoperative venous thromboembolism prophylaxis using enoxaparin 40 mg twice daily or enoxaparin 0.5 mg/kg twice daily. Patients were randomized after surgery and received the first enoxaparin dose at 8 hours after surgery. Primary hypotheses were (1) weight-based administration is noninferior to a fixed dose for avoiding underanticoagulation (anti-factor Xa <0.2 IU/ml) and (2) weight-based administration is superior to fixed-dose administration for avoiding overanticoagulation (anti-factor Xa >0.4 IU/ml). Secondary endpoints were 90-day venous thromboembolism and bleeding. RESULTS: In total, 295 patients were randomized, with 151 assigned to fixed-dose and 144 to weight-based administration of enoxaparin. For avoidance of under anticoagulation, weight-based administration had a greater effectiveness (79.9 percent versus 76.6 percent); the 3.3 percent (95 percent CI, -7.5 to 12.5 percent) greater effectiveness achieved statistically significant noninferiority relative to the a priori specified -12 percent noninferiority margin (p = 0.004). For avoidance of overanticoagulation, weight-based enoxaparin administration was superior to fixed-dose administration (90.6 percent versus 82.2 percent); the 8.4 percent (95 percent CI, 0.1 to 16.6 percent) greater effectiveness showed significant safety superiority (p = 0.046). Ninety-day venous thromboembolism and major bleeding were not different between fixed-dose and weight-based cohorts (0.66 percent versus 0.69 percent, p = 0.98; 3.3 percent versus 4.2 percent, p = 0.72, respectively). CONCLUSION: Weight-based administration showed superior pharmacokinetics for avoidance of underanticoagulation and overanticoagulation in postoperative patients receiving prophylactic enoxaparin. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Fixed or Weight-Tiered Enoxaparin After Thoracic Surgery for Venous Thromboembolism Prevention.

BACKGROUND: Venous thromboembolism is an important patient safety issue in thoracic surgery patients. The optimal enoxaparin dose remains unclear. This multicenter pre/post clinical trial compared the pharmacokinetics of fixed versus weight-tiered enoxaparin, and their impact on 90-day venous thromboembolism and bleeding. METHODS: Thoracic surgery patients were prospectively enrolled using a pre/post study design. Cohort 1 received enoxaparin 40 mg daily, and cohort 2 received a weight-tiered regimen: less than 70 kg received 30 mg daily; 70 kg to 89.9 kg received 40 mg once daily; and 90 kg or more received 50 mg daily. The primary study outcome was peak anti-factor Xa levels in response to fixed or weight-tiered enoxaparin. Secondary outcomes included trough anti-factor Xa, 90-day symptomatic venous thromboembolism, and 90-day clinically relevant bleeding. RESULTS: One hundred thirty-one patients were prospectively enrolled, including 65 in the fixed-dose cohort and 66 in the weight-tiered cohort. No patient was lost to follow-up. Weight-tiered enoxaparin was not significantly more likely to produce adequate anticoagulation (peak anti-factor Xa 0.3 IU/mL or greater) when compared with fixed-dose enoxaparin (44.3% vs 48.2%, P = .67). Weight-tiered enoxaparin was not more likely to avoid over-anticoagulation (peak anti-factor Xa 0.5 IU/mL or greater) when compared with fixed-dose enoxaparin (3.3% vs 3.6%, P = 1.00). The groups had no significant difference in trough anti-factor Xa. Observed rates of 90-day symptomatic venous thromboembolism and clinically relevant bleeding were low (0% and 3.1%, respectively) and were not significantly different between groups. CONCLUSIONS: This multicenter pre/post clinical trial did not show a pharmacokinetic advantage to weight-tiered enoxaparin, when compared with fixed-dose enoxaparin, in thoracic surgery patients. (Clinicaltrials.gov identifier: NCT03251963.).

Underdosing of Prophylactic Enoxaparin Is Common in Orthopaedic Trauma and Predicts 90-Day Venous Thromboembolism.

OBJECTIVES: To determine the feasibility and impact of real-time anti-factor Xa (aFXa) level monitoring and enoxaparin dose adjustment in orthopaedic trauma. To examine the adequacy of standard fixed-dose enoxaparin chemoprophylaxis and to examine whether patient-specific factors influence enoxaparin metabolism. DESIGN: Prospective cohort. SETTING: Academic Level-I trauma center. PATIENTS: Postoperative adult orthopaedic trauma patients undergoing acute fracture or nonunion surgery of the pelvis, acetabulum, or lower extremity placed on 30 mg of enoxaparin twice daily. INTERVENTION: Peak steady-state aFXa levels were drawn with a goal range of 0.2-0.4 IU/mL. Patients with out-of-range levels underwent a 10-mg dose adjustment followed by repeat aFXa draws. MAIN OUTCOME MEASURES: Peak and trough aFXa levels, 90-day venous thromboembolism, and bleed events. RESULTS: Of 109 enrolled patients, 43% had inadequate initial peak aFXa levels (aFXa < 0.2 IU/mL) with standard dosing. Higher gross weight, acetabular surgery, and operation length predicted low aFXa levels (P < 0.001, 0.006, 0.004, respectively). Dose adjustment increased the proportion of patients with in-range aFXa levels from 53.2% to 87.8% (P < 0.001). Patients with low aFXa levels during hospitalization or at discharge had significantly higher 90-day deep vein thrombosis and pulmonary embolism rates compared to those with adequate aFXa levels (deep vein thrombosis 12% vs. 1.36%; P = 0.023, pulmonary embolism 8% vs. 0%; P = 0.027). There were no major bleed events. CONCLUSIONS: Patients receiving inadequate enoxaparin chemoprophylaxis were at significantly increased risk of 90-day venous thromboembolism. Standard fixed-dose enoxaparin provided inadequate chemoprophylaxis in 43% of postoperative orthopaedic trauma patients, which significantly improved with dose adjustment. Weight, acetabular surgery, and operation length predicted inadequate enoxaparin prophylaxis. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Double-Blind Randomized Clinical Trial to Examine the Pharmacokinetic and Clinical Impacts of Fixed Dose versus Weight-based Enoxaparin Prophylaxis: A Methodologic Description of the FIxed or Variable Enoxaparin (FIVE) Trial.

Venous thromboembolism is an important patient safety in plastic surgery, and multiple clinical trials in the past 10 years have provided increased understanding of the risks and benefits of venous thromboembolism prevention strategies. This paper provides an exhaustive discussion of the rationale behind and methodology for an in progress randomized double-blind clinical trial in plastic surgery inpatients, in which the 2 study arms are enoxaparin 40 mg twice daily and enoxaparin 0.5 mg/kg twice daily. The trial's primary aims are to: (1) demonstrate whether enoxaparin 0.5 mg/kg twice daily is superior to enoxaparin 40 mg twice daily for the pharmacokinetic endpoint of overanticoagulation (anti-Factor Xa > 0.4 IU/mL) and (2) demonstrate whether enoxaparin 0.5 mg/kg twice daily is not inferior to enoxaparin 40 mg twice daily for the pharmacokinetic endpoint of underanticoagulation (anti-Factor Xa < 0.2 IU/mL). The results of this trial will provide Level I evidence to help guide plastic surgeon's choice of postoperative prophylactic anticoagulation.

Assessment of Anti-Factor Xa Levels of Patients Undergoing Colorectal Surgery Given Once-Daily Enoxaparin Prophylaxis: A Clinical Study Examining Enoxaparin Pharmacokinetics.

Importance: Between 4% and 12% of patients undergoing colorectal surgery and receiving enoxaparin, 40 mg per day, have a postoperative venous thromboembolism (VTE) event. An improved understanding of why "breakthrough" VTE events occur despite guideline-compliant prophylaxis is an important patient safety question. Objective: To determine the proportion of patients undergoing colorectal surgery who received adequate anticoagulation based on peak anti-factor Xa (aFXa) levels while receiving enoxaparin at 40 mg per day. Design, Setting, and Participants: This prospective, nonrandomized clinical trial was conducted between February 2017 and July 2018 with 90-day follow-up at a quaternary academic medical center in the Intermountain West and included patients undergoing colorectal surgery who had surgery after receiving general anesthesia, were admitted for at least 3 days, and received enoxaparin, 40 mg once daily. Interventions: All patients had aFXa levels measured after receiving enoxaparin 40 mg per day. Patients whose aFXa level was out of range entered the trial's interventional arm where real-time enoxaparin dose adjustment and repeated aFXa measurement were performed. Main Outcomes and Measures: Primary outcome: in-range peak aFXa levels (goal range, 0.3-0.5 IU/mL) with enoxaparin, 40 mg per day. Secondary outcomes: (1) in-range trough aFXa levels (goal range, 0.1-0.2 IU/mL) and (2) the proportion of patients with in-range peak aFXa levels from enoxaparin, 40 mg once daily, vs the real-time enoxaparin dose adjustment protocol. Results: Over 16 months, 116 patients undergoing colorectal surgery (65 women [56.0%]; 99 white individuals [85.3%], 13 Hispanic or Latino individuals [11.2%], and 4 Pacific Islander individuals [3.5%]; mean [range] age, 52.1 [18-85] years) were enrolled. Among 106 patients (91.4%) whose peak aFXa level was appropriately drawn, 72 (67.9%) received inadequate anticoagulation (aFXa < 0.3 IU/mL) with enoxaparin, 40 mg per day. Weight and peak aFXa levels were inversely correlated (r2 = 0.38). Forty-seven patients (77%) had a trough aFXa level that was not detectable (ie, most patients had no detectable level of anticoagulation for at least 12 hours per day). Real-time enoxaparin dose adjustment was effective. Patients were significantly more likely to achieve an in-range peak aFXa with real-time dose adjustment as opposed to fixed dosing alone (85.4% vs 29.2%, P < .001). Conclusions and Relevance: This study supports the finding that most patients undergoing colorectal surgery receive inadequate prophylaxis from enoxaparin, 40 mg once daily. These findings may explain the high rate of "breakthrough" VTE observed in many clinical trials. Trial Registration: ClinicalTrials.gov identifier: NCT02704052.

Twice-Daily Enoxaparin among Plastic Surgery Inpatients: An Examination of Pharmacodynamics, 90-Day Venous Thromboembolism, and 90-Day Bleeding.

BACKGROUND: Low anti-factor Xa level, indicative of inadequate enoxaparin dosing, has a significant association with 90-day venous thromboembolism events. The authors examined the pharmacodynamics of enoxaparin 40 mg twice daily and its correlation with anti-factor Xa level, postoperative venous thromboembolism, and bleeding. METHODS: Adult patients were admitted after plastic and reconstructive surgery and received enoxaparin 40 mg twice daily. Peak anti-factor Xa levels, which quantify enoxaparin's antithrombotic effect, were drawn, with a goal level of 0.2 to 0.4 IU/ml. Ninety-day symptomatic venous thromboembolism and clinically relevant bleeding were identified. RESULTS: The authors enrolled 118 patients who received enoxaparin 40 mg twice daily. Of these patients, 9.6 percent had low peak anti-factor Xa levels (<0.2 IU/ml), 62.6 percent had in-range peak anti-factor Xa levels (0.2 to 0.4 IU/ml), and 27.8 percent had high anti-factor Xa levels (>0.4 IU/ml). With enoxaparin 40 mg twice daily, 90.4 percent of patients received at least adequate prophylaxis. Patient weight predicted the rapidity of enoxaparin metabolism. Zero acute 90-day venous thromboembolism occurred. Eight patients (6.8 percent) had clinically relevant 90-day bleeding: clinical consequences ranged from cessation of enoxaparin prophylaxis to transfusion to operative hematoma evacuation. CONCLUSIONS: When enoxaparin 40 mg twice daily is provided, 90 percent of patients receive at least adequate venous thromboembolism prophylaxis (anti-factor Xa level >0.2 IU/ml). However, 27 percent of the overall population is overtreated (anti-factor Xa level >0.4 IU/ml). These pharmacodynamics data likely explain the low rate of 90-day acute venous thromboembolism (0 percent) and the high rate of clinically relevant bleeding (6.8 percent) observed. Future studies are needed to better optimize the risks and benefits of enoxaparin prophylaxis in plastic and reconstructive surgery patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Enoxaparin 40 mg per Day Is Inadequate for Venous Thromboembolism Prophylaxis After Thoracic Surgical Procedure.

BACKGROUND: Many patients undergoing thoracic surgical procedures have venous thromboembolism (VTE) events despite the receipt of chemical prophylaxis. Enoxaparin's pharmacologic impact can be quantified by using anti-Factor Xa (aFXa) levels. We hypothesized that enoxaparin 40 mg once daily would be inadequate for most inpatients undergoing thoracic surgical procedures and that a real-time dose adjustment algorithm would be effective. METHODS: This prospective clinical trial enrolled inpatients who were to undergo a thoracic surgical procedure and placed on enoxaparin 40 mg once daily for VTE prophylaxis after surgical procedures. aFXa levels were used to measure the anticoagulant effect of enoxaparin once steady state had been reached. Patients whose aFXa levels were out of range received real-time enoxaparin dose adjustment and had repeat aFXa levels drawn. RESULTS: Ninety-three inpatients undergoing thoracic surgical procedures were prospectively enrolled. The majority of patients (67.4%) had low peak aFXa levels (<0.3 IU/mL), indicative of inadequate enoxaparin prophylaxis, and 30.3% of patients had in-range aFXa levels (0.3 to 0.5 IU/mL). Patient weight had a moderate correlation (r2 0.38) with peak aFXa level. Patient weight, female sex, and preoperative creatinine were independent predictors of peak aFXa in a linear regression model. Real-time, protocol-driven enoxaparin dose adjustment allowed a significantly increased proportion of patients to achieve in-range aFXa levels (30.3% vs 97.6%, p < 0.001). CONCLUSIONS: Enoxaparin 40 mg once daily is inadequate for most inpatients undergoing thoracic surgical procedures, based on a pharmacodynamic study of aFXa levels. Future research should examine the impact of weight-based once daily enoxaparin dosing versus twice daily enoxaparin dosing on prophylaxis adequacy.

The Impact of Once- versus Twice-Daily Enoxaparin Prophylaxis on Risk for Venous Thromboembolism and Clinically Relevant Bleeding.

BACKGROUND: Venous thromboembolism is a life- or limb-threatening complication that occurs in plastic surgery patients. At present, the optimal dose of enoxaparin that balances the risk of venous thromboembolism and the risk of medication-related adverse drug events-specifically, bleeding-remains unknown. METHODS: This study compared pharmacodynamic and clinical outcomes, including 90-day venous thromboembolism and 90-day clinically relevant bleeding, between two prospectively performed clinical trials whose sole difference was postoperative anticoagulation strategy. Patients in trial 1 received enoxaparin 40 mg once daily for the duration of inpatient stay, and patients in trial 2 received enoxaparin 40 mg twice daily for the duration of inpatient stay. The study also examined the potential impact of a weight-based twice-daily prophylaxis strategy to achieve in-range anti-factor Xa levels. RESULTS: The study compared 94 patients who received once-daily enoxaparin to 118 patients who received twice-daily enoxaparin. Twice-daily enoxaparin was associated with a significant decrease in 90-day acute venous thromboembolism (0 percent versus 5.3 percent; p = 0.012) and a nonsignificant increase in 90-day clinically relevant bleeding (6.8 percent versus 3.2 percent; p = 0.25). Twice-daily enoxaparin at 0.4 to 0.5 mg/kg may allow an increased proportion of patients to avoid both inadequate anticoagulation and overanticoagulation, based on anti-factor Xa levels. CONCLUSIONS: Twice-daily enoxaparin is superior to once-daily enoxaparin for 90-day acute venous thromboembolism risk reduction. Twice-daily enoxaparin may increase clinically relevant bleeding, although observed differences in this study were not significant. Weight-based twice-daily enoxaparin dosing may optimize the risks and benefits of prophylactic anticoagulation after plastic and reconstructive surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Comparison of face-to-face interaction and the electronic medical record for venous thromboembolism risk stratification using the 2005 Caprini score.

OBJECTIVE: Perioperative venous thromboembolism (VTE) risk can be quantified with the 2005 Caprini score. The Caprini score has previously been validated by review of the electronic medical record (EMR) in >3000 plastic surgery patients. However, the accuracy of Caprini-based risk stratification using the EMR, as opposed to face-to-face contact with the patient, remains unknown. METHODS: Plastic and reconstructive surgery patients who had surgery under general anesthesia, required postoperative admission, and were started on enoxaparin prophylaxis were identified. The 2005 Caprini scores were calculated retrospectively using EMR review only (no direct contact with the patients) to establish cohort 1. The 2005 Caprini scores were calculated prospectively using face-to-face interaction with the patients, followed by EMR review, to establish cohort 2. For all included patients, EMR review or face-to-face screening was personally performed by the authors. We compared the proportions of patients with identified Caprini risk factors and the aggregate risk scores of patients between cohorts. RESULTS: Complete data were available for 536 unique patients in the EMR review cohort and 207 unique patients in the face-to-face cohort. Patients whose risk scores were calculated face to face had higher Caprini scores than those calculated by EMR review alone. The face-to-face cohort had a higher proportion of patients risk stratified as Caprini 7-8 (29.5% vs 24.8%) and Caprini >8 (26.6% vs 10.5%) compared with the EMR review cohort. Patients risk stratified by face-to-face discussion were significantly more likely to be stratified into a higher risk Caprini stratum. Face-to-face discussion identified a 2-fold increase in patients with personal history of deep venous thrombosis (12.6% vs 6.3%; P = .005), a 3-fold increase in patients with family history of VTE (16.9% vs 5.2%; P < .001), and a 20-fold increase in patients with personal history of multiple lost pregnancies (13.6% vs 0.6%; P < .001) compared with EMR review. Observed differences for family history of VTE and history of pregnancy loss persisted after propensity score analysis, created using component variables in the 2005 Caprini score plus gender; this supports the conclusion that observed differences were not due to site variation or case mix. CONCLUSIONS: When it is used in isolation, the EMR may provide inaccurate estimation of patient-level VTE risk using the 2005 Caprini score. This study demonstrates that EMR review may miss key VTE risk factors, such as personal or family history of VTE, history of pregnancy loss, and others; this omission results in lower estimates of perioperative VTE risk. The importance of provider-patient interaction for accurate VTE risk stratification cannot be overstated.

Anti-Factor Xa measurements in acute care surgery patients to examine enoxaparin dose.

BACKGROUND: The purpose of this study was to determine if fixed dose enoxaparin prophylaxis provided effective anticoagulation for acute care surgery patients and to examine whether a real-time enoxaparin dose adjustment algorithm optimized anticoagulation. METHODS: Acute care surgical patients placed on enoxaparin prophylaxis 30 mg twice daily were recruited prospectively. Peak steady state aFXa levels were drawn with a goal peak aFXa range of 0.2-0.4 IU/ml. A real time dose adjustment algorithm was implemented for patients with out-of-range levels. RESULTS: Fifty five patients were included. 56.4% of patients had low aFXa levels (<0.2 IU/mL). Real-time enoxaparin dose adjustment significantly increased the proportion of patients who achieved in-range peak aFXa levels, compared to standard dosing (74.5% vs 41.8%, p < 0.001). Patients with initial inadequate peak aFXa levels had a higher rate of 90-day post-operative VTE, although not statistically significant (16.1% vs. 8.3%, p = 0.50). CONCLUSION: The majority of acute care surgery patients receive inadequate VTE prophylaxis with fixed enoxaparin dosing.

Weight-Based Dosing for Once-Daily Enoxaparin Cannot Provide Adequate Anticoagulation for Venous Thromboembolism Prophylaxis.

BACKGROUND: Surgeons commonly provide enoxaparin prophylaxis to high-risk patients to decrease venous thromboembolism risk. The authors' prior work demonstrated that most patients receive inadequate venous thromboembolism prophylaxis, based on anti-factor Xa level, when enoxaparin 40 mg/day is provided and that peak anti-factor Xa level correlates with weight. This study models a weight-based strategy for daily enoxaparin prophylaxis and its impact on anti-factor Xa levels. METHODS: The authors enrolled plastic surgery patients who received enoxaparin 40 mg/day and had anti-factor Xa levels drawn. The enoxaparin dose of 40 mg was converted to a milligram-per-kilogram dose for each patient. Stratified analysis examined the milligram-per-kilogram dose that produced low, in-range, and high anti-factor Xa levels to identify the appropriate milligram-per-kilogram dose to optimize venous thromboembolism prevention and bleeding events. RESULTS: Among 94 patients, weight-based dosing ranged from 0.28 to 0.94 mg/kg once daily. For peak and trough anti-factor Xa levels, there was nearly complete overlap for milligram-per-kilogram dosing that produced low versus in-range anti-factor Xa levels. For peak anti-factor Xa, there was nearly complete overlap for milligram-per-kilogram dosing that produced in-range versus high anti-factor Xa levels. Mean milligram-per-kilogram dose was not significantly different between patients who did or did not have postoperative venous thromboembolism (0.41 mg/kg versus 0.52 mg/kg; p = 0.085) or clinically relevant bleeding (0.48 mg/kg versus 0.51 mg/kg; p = 0.73). CONCLUSIONS: Alterations in enoxaparin dose magnitude based on patient weight cannot allow a high proportion of patients to achieve appropriate anti-factor Xa levels when once-daily enoxaparin prophylaxis is provided. Future research should examine the impact of increased enoxaparin dose frequency on anti-factor Xa levels, venous thromboembolism events, and bleeding. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Inadequate Enoxaparin Dosing Predicts 90-Day Venous Thromboembolism Risk among Plastic Surgery Inpatients: An Examination of Enoxaparin Pharmacodynamics.

BACKGROUND: Evidence-based plastic surgery guidelines support the effectiveness of once-daily enoxaparin prophylaxis. Despite prophylaxis, one in 25 highest risk patients has a venous thromboembolism event. The authors examined the pharmacodynamics of standard enoxaparin doses in plastic surgery patients to examine whether patient-level factors predict enoxaparin metabolism, whether inadequate enoxaparin dose predicts downstream venous thromboembolism events, and whether a pharmacist-driven dose-adjustment protocol was effective. METHODS: The authors recruited adult plastic surgery patients who received postoperative enoxaparin at 40 mg/day. Steady-state peak anti-factor Xa levels, a marker of enoxaparin effectiveness and safety, were determined. Patients with out-of-range anti-factor Xa levels had real-time dose adjustment based on a written protocol. Patients were followed for 90-day venous thromboembolism events. RESULTS: Ninety-four patients were recruited, and 44 percent had in-range peak anti-factor Xa levels in response to standard enoxaparin dosing. Patient-level factors including extent of surgical injury and gross weight were independent predictors of enoxaparin metabolism. Patients with low anti-factor Xa levels were significantly more likely to have 90-day venous thromboembolism (10.2 percent versus 0 percent; p = 0.041). Real-time dose adjustment allowed a significantly increased proportion of patients to have in-range levels (67.1 percent versus 44.3 percent; p = 0.002). CONCLUSIONS: Based on pharmacodynamic data, the majority of plastic surgery patients receive inadequate enoxaparin prophylaxis using fixed dosing. Patient-level factors can predict how patients will metabolize enoxaparin, and patients who receive inadequate enoxaparin prophylaxis are significantly more likely to have downstream venous thromboembolism events. Individualization of enoxaparin prophylaxis may minimize perioperative venous thromboembolism risk and further improve patient safety after plastic and reconstructive surgery procedures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.