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

Abstract

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Pannucci received grant support from the Association for Academic Surgery's Joel J. Roslyn Award during the conduct of the study. Dr Pickron reported personal fees from Intuitive Surgical outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Clinical Study Protocol Including Real-time Anti–Factor Xa (aFXa) Level Monitoring and Enoxaparin Dose Adjustment

Figure 2.. Peak Anti–Factor Xa (aFXa) Stratified by Weight

The shaded area denotes peak aFXa levels that are considered in range.

Figure 3.. Enoxaparin Dose Grouped by Anti–Factor Xa (aFXa) Level