Results of a quality improvement study suggest that current time-based guidelines for prophylactic enoxaparin before neuraxial procedures may need to be amended.
Despite being more than 24 hours removed from a treatment dose of enoxaparin, nearly 60% of patients presenting for surgery had anti–factor Xa levels within the prophylactic or therapeutic range. Elderly patients appeared to be at particular risk, the authors noted, as over 80% of patients older than 70 years of age showed elevated anticoagulant activity. According to the researchers, monitoring anti–factor Xa levels after prophylactic enoxaparin administration could be a useful safeguard for patients receiving neuraxial anesthesia.
“Our findings suggest that the current time-based guidelines may not be as conservative as necessary and that laboratory testing for patients on enoxaparin may have more value than previously thought,” said James Turner, MD, a regional anesthesia and acute pain medicine fellow at Wake Forest Baptist Medical Center, in Winston-Salem, N.C.
As Dr. Turner reported, enoxaparin—a factor Xa inhibitor—is used to prevent and treat thromboembolism but also is commonly used off-label in the perioperative setting as a bridge for patients on chronic anticoagulation before surgery. Although current American Society of Regional Anesthesia and Pain Medicine (ASRA) guidelines recommend that a minimum of 24 hours should elapse following a treatment dose of enoxaparin before neuraxial procedures are performed, Dr. Turner said caution is warranted in patients who are elderly, low in weight or obese, and for patients with severe renal impairment.
After observing elevated anti–factor Xa levels in patients in clinical practice, Dr. Turner and his colleagues performed a prospective, quality improvement–based, observational study to investigate whether residual anticoagulant effect was still present at 24 hours after the last dose of enoxaparin in patients presenting for elective surgery.
After confirming the enoxaparin dose and the timing of the last administration for the 25 enrolled patients, they obtained a venous blood sample<2028>as close to 24 hours after the last dose as possible. Anti–factor Xa levels were then calculated using a chromogenic assay, a hybrid calibration curve for heparin and enoxaparin, and a BCS XP Coagulation Analyzer (Siemens Healthineers).
Six of the 25 patients were excluded because they were prescribed other anticoagulants that would have affected laboratory results.
As Dr. Turner reported at the 2017 annual meeting of ASRA (abstract 3379), investigators found that 58% of patients (10/19) had anti–factor Xa levels above a prophylactic or therapeutic range despite having met the 24-hour guideline.
Age was a significant factor, said Dr. Turner, as 83% (10/12) of patients who were aged 70 years or older had levels that were in the prophylactic or therapeutic peak target range, despite having waited at least 24 hours since their last dose. In addition, only one patient younger than 70 was above the prophylactic range for anti–factor Xa level.
Finally, investigators also observed a trend demonstrating that patients with increasing serum creatinine values had increased anti–factor Xa levels.
“As creatinine clearance decreases, the effect of enoxaparin is seen to be prolonged as evidenced by elevated anti-Xa levels,” Dr. Turner explained. “For this reason, we found that even patients with mild or moderate renal impairment may be at risk, not just those with severe renal impairment.”
According to Dr. Turner, these findings suggest that anti–factor Xa level monitoring as found in other specialties might be useful following enoxaparin administration.
“This begs the question of whether we should be using anti-Xa levels in the same way that we use INRs [international normalized ratios] for patients on warfarin or a partial thromboplastin time for patients on heparin,” Dr. Turner said. “Anti-Xa level monitoring may help ensure that excessive residual anticoagulant effects are not present before high-risk invasive procedures are performed.”
Dr. Turner emphasized that further investigation is needed to determine the threshold of residual anticoagulant activity that places a patient at risk for neuraxial bleeding. Researchers at Wake Forest Baptist are planning a larger prospective study to explore whether a longer time interval can provide more confidence of minimal residual anticoagulant activity.
Still, Katharine H. Fleischmann, MD, assistant professor of anesthesiology at Massachusetts General Hospital, in Boston, questioned the ease of using anti–factor Xa levels for patient monitoring.
“How cooperative was your laboratory setting in obtaining a factor Xa assay, and how can we bring that opportunity not just to large institutions like ours but to the community?” Dr. Fleischmann asked.
“Once our labs get the sample, it takes approximately 10 minutes to run the test,” Dr. Turner said. “You wait longer for an INR, which we do for warfarin, than you do for this assay. We suggest that maybe it’s time to do the same thing for enoxaparin that you do for warfarin. I don’t know what percentage of smaller hospitals have the assay necessary to do this, but at our institution, it’s a pretty reasonable amount of time.”