Is enoxaparin, 40 mg per day, adequate, based on pharmacokinetics, for venous thromboembolism prophylaxis in patients undergoing colorectal surgery?
This nonrandomized clinical trial enrolled 116 patients undergoing colorectal surgery who received enoxaparin, 40 mg per day, for venous thromboembolism prophylaxis at a single institution. The study found that among 106 patients with appropriately timed anti–factor Xa levels, a marker of the extent of anticoagulation and enoxaparin effectiveness, 72 patients (67.9%) received inadequate anticoagulation.
This study demonstrates that two-thirds of patients undergoing colorectal surgery have inadequate anti–factor Xa levels in response to enoxaparin, 40 mg once daily, and that a higher weight is associated with lower anti–factor Xa levels.
Between 4% and 12% of patients undergoing colorectal surgery and receiving enoxaparin, 40 mg per day, have a postoperative VTE event. An improved understanding of why “breakthrough” VTE events occur despite guideline-compliant prophylaxis is an important patient safety question.
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.
All patients had aFXa levels measured after receiving enoxaparin 40mg 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.
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.
ClinicalTrials.gov identifier: NCT02704052
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Pannucci CJ, Fleming KI, Bertolaccini CB, Prazak AM, Huang LC, Pickron TB. Assessment of Anti–Factor Xa Levels of Patients Undergoing Colorectal Surgery Given Once-Daily Enoxaparin Prophylaxis: A Clinical Study Examining Enoxaparin Pharmacokinetics. JAMA Surg. Published online May 22, 2019. doi:10.1001/jamasurg.2019.1165
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