Fixed-dose enoxaparin prophylaxis often inadequate for colorectal surgery

By Marilynn Larkin

NEW YORK (Reuters Health) - 30/5/2019

Most patients undergoing colorectal surgery don't get adequate anticoagulation from the FDA-approved 40 mg daily dose of enoxaparin, possibly setting the stage for breakthrough venous thromboembolism, researchers say.

"The current paradigm of care is a one-size-fits-all mentality for clot prevention," Dr. Christopher Pannucci of the University of Utah in Salt Lake City told Reuters Health by phone. "Even though we know individualization is beneficial in other paradigms, when it comes to treating clots, most people treat every patient the same way, asking simply, 'should I give prophylaxis or not?'"

"But when you treat everyone the same, that treatment may be inadequate for the majority of people," he said. "We showed two out of three colorectal surgery patients get inadequate prophylaxis. In other specialties, when prophylaxis is inadequate, it's been correlated with 90-day significant clots."

"There's an opportunity for us to improve care by at least consideration of care individualization," he said.

Dr. Pannucci and colleagues studied 106 patients undergoing colorectal surgery who were admitted to the medical center for at least three days, received enoxaparin 40 mg once daily and had anti-factor Xa (aFXa) levels measured afterwards. Participants' mean age was 52, 56% were women, and 85%, white.

The primary outcome was in-range peak aFXa levels (goal range, 0.3-0.5 IU/mL) with enoxaparin 40 mg daily. Those whose aFXa levels were out of range after enoxaparin entered the interventional arm, in which real-time enoxaparin dose adjustment and repeated aFXa measurements were performed.

Secondary outcomes included in-range trough aFXa levels (goal range, 0.1-0.2 IU/mL) and the proportion of patients with in-range peak aFXa levels from 40 mg once daily enoxaparin versus real-time enoxaparin dose adjustment.

As reported online May 22 in JAMA Surgery, 72 (67.9%), patients received inadequate anticoagulation (aFXa < 0.3 IU/mL) with once-daily 40 mg enoxaparin. Thirty-one (29.3%) received adequate anticoagulation (0.3-0.5 IU/mL) and three (2.8%) received overanticoagulation.

After adjustment for various patient-related factors, only weight had a significant and independent association with peak aFXa levels - i.e., they were inversely correlated.

Sixty-nine patients (65.1%) had trough steady-state aFXa levels drawn while receiving enoxaparin 40 mg daily. Eight (7.5%) were excluded for inappropriate timing, leaving 61 patients, of whom 47 (77.1%) had undetectable aFXa activity 12 hours after the third enoxaparin dose. Thirteen (21.3%) had an in-range trough level (0.1-0.2 IU/mL) and one (1.6%) had a high trough level.

Patients were significantly more likely to achieve an in-range peak aFXa with real-time dose adjustment versus fixed dosing alone (85.4% vs. 29.2%).

Three venous thromboembolism events occurred in the entire cohort during the 90-day follow-up period; however, there was no significant difference in event occurrence between those with low versus in-range aFXa levels.

Dr. Juan Arcelus of the University of Granada, Spain, author of a related editorial, commented in an email to Reuters Health, "AFXa levels are used to monitor the effect of low molecular weight heparins on clotting in some clinical scenarios, as in patients with extreme weights and renal failure."

"In this study," he noted, "those levels were too low in two-thirds of the patients receiving 40 mg of enoxaparin once a day after colorectal surgery. However, there was not a correlation between those levels and the actual incidence of postoperative venous thrombosis. Similar results have been reported by other investigators using other heparins."

"Based on the results of this study, clinicians might consider prescribing enoxaparin twice a day after colorectal surgery, particularly in obese patients," he suggested. "Apart from increasing and adjusting heparin doses, another important measure to reduce the incidence of this complication is to prolong prophylaxis for up to 30 days postoperatively in patients operated on for colorectal cancer, as recommended in recent guidelines."


JAMA Surg 2019.

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