The current ASRA anticoagulation guidelines recommend that a minimum of 24-hours should elapse following a treatment dose of Enoxaparin (1mg/kg twice daily or 1.5mg/kg once daily) before a neuraxial procedure is performed1. Enoxaparin, a factor Xa inhibitor, is frequently used to both prevent and treat thromboembolism, but is also commonly used off-label in the perioperative setting as a bridge for patients that are chronically anticoagulated prior to surgery, such as those taking Warfarin. Enoxaparin is an attractive option for perioperative use secondary to its purported predictable pharmacologic profile and the lack of recommended routine blood monitoring. In fact, the ASRA guidelines also recommend against the routine use of anti-Xa level monitoring for patients on Enoxaparin1. Recently, an increased rate of neurologic sequelae has been reported following neuraxial catheter placement and/or removal in coagulopathic patients, suggesting a potential need to be hyper- vigilant when considering a neuraxial procedure in this patient population2.
Despite the current ASRA guidelines we have noted in our clinical practice that anti-Xa levels are often still in the reported peak prophylactic range (0.2-0.5 IU/ml) 24-hours or more following a treatment dose of Enoxaparin, and occasionally are still in the reported peak therapeutic range (0.5-1.0 IU/ml)3-4. For this reason, we decided to perform a prospective quality-improvement based observational study to investigate whether residual anticoagulant effect was still present 24-hours or more following the last treatment dose of enoxaparin in patients presenting for elective surgery.
Materials and Methods
•25 patients were involved in this observational case series.
•IRB approval was subsequently obtained and waiver of informed consent was obtained.
•After confirming the Enoxaparin dose and the timing of the last administration, a venous blood sample was obtained as close to 24-hours as possible following the last dose.
•Anti-Xa levels were calculated using a chromogenic assay, a hybrid calibration curve for Heparin and Enoxaparin, and a BCSXP Coagulation Analyzer5.
•Originally, 25 patients were included in the study. However, 6 were excluded as they been “bridged” from other anti-Xa inhibiting medications that could have altered the laboratory results.
•Of the remaining patients, we found that 10/19 (Figure 1) had an anti-Xa level that was within the accepted prophylactic peak target range (0.2-0.5 units/ml).
•One additional patient had an anti-Xa level that was within the accepted peak target treatment range (0.5-1.0 units/ml).
•All patients met ASRA guidelines for a 24-hour washout except one, whose lab was drawn at 23.25 hours.
•10/12 patients aged 70-years or older, regardless of the time of lab draw, had levels that were in the prophylactic or therapeutic peak target range, despite having waited at least 24-hours since their last dose (Figure 2).
•There appeared to be a trend which suggests that patients with increasing serum creatinine values had increased anti-Xa levels (Figure 3)
•Anti-Xa levels are specific to heparin and enoxaparin
•Of the patients presenting for surgery on treatment dose Enoxaparin, we found that a significant number (58%) still had elevated levels of anticoagulant activity, despite being 24-hours or more removed from their last dose as suggested by the current ASRA guidelines1.
•Elderly patients appeared to be at particular risk as 83% of patients > 70-years old had elevated anti-Xa level activity.
•Our findings suggests 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.
•Several other recent studies involving various patient populations have also noted variability in both peak and trough anti-Xa levels following prophylactic Enoxaparin administration, further suggesting that monitoring may be beneficial6-8.
•Should Anti-Xa monitoring be utilized in similar fashion to an International Normalized Ratio (INR) for patients on Warfarin or a Partial Thromboplastin Time (PTT) for patients on Heparin?
•We suggest that it may be time to adopt a similar approach and to utilize anti-Xa level monitoring to ensure that excessive residual anticoagulant effects are not present before high-risk invasive procedures are performed.
•While we do not yet know the anti-Xa level at which a patient’s risk of neuraxial bleeding is acceptable, this study clearly suggests that further investigation is needed.
•We are currently planning a larger prospective study to determine whether a longer time interval can provide more confidence of minimal residual anticoagulant activity.