Residual Enoxaparin Activity, Anti-Xa Levels, and Concerns About the American Society of Regional Anesthesia and Pain Medicine Anticoagulation Guidelines

Abstract

Currently, the American Society of Regional Anesthesia and Pain Medicine (ASRA) anticoagulation guidelines recommend that before the performance of a neuraxial procedure a minimum of 24 hours should elapse following a treatment dose of enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily). The guidelines have since their inception also consistently recommended against the routine use of anti-Xa level monitoring for patients receiving enoxaparin. However, we noted in our clinical practice that anti-Xa levels were frequently still elevated despite patients meeting the time-based recommendation for treatment dose enoxaparin. To further investigate the possibility that residual anticoagulant activity may persist longer than 24 hours after a treatment dose of enoxaparin, we assessed anti-Xa level activity in patients presenting for elective surgery. Despite nearly universal compliance with ASRA's anticoagulation guidelines (1 sample was drawn at 23.25 hours), anti-Xa activity was found to be elevated in 11 of 19 patients. While 10 patients had an anti-Xa level within the peak prophylactic range (0.2-0.5 IU/mL), 1 patient's level was found to still be in the peak therapeutic range (0.5-1.0 IU/mL). These findings suggest that significant anticoagulant activity may persist longer than previously appreciated after the last treatment dose of enoxaparin and that the current time-based ASRA recommendation may not be conservative enough. Further research is needed to delineate the level of anti-Xa activity below which it is likely safe to proceed with a neuraxial procedure, but it may be time to reconsider the utility of anti-Xa level monitoring when it is available.

Residual anti-Xa activity in plasma of patients presenting for electively planned neuraxial regional anesthesia

“…Even after waiting nearly 36 hours, more than 10% of patients still had levels of anti-Xa activity within the prophylactic range. Our findings are in line with a previous work conducted by Henshaw et al 8. In their report, 11 of 19 (57.9%) patients showed elevated anti-Xa levels within prophylactic range despite an interval of 24 hours after receiving therapeutic dose enoxaparin.…”

“…After four to five half-lives, the residual activity of LMWH should be sufficiently decreased, in theory, allowing neuraxial blockade to be performed without a significant increased risk of bleeding 5. While the time interval has been well proven to be reasonably safe for prophylactic dosing of LMWH,7 there is doubt if these pharmacokinetic based time intervals are really sufficient for patients receiving therapeutic anticoagulation 8…”

Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy

“…36 A recent series of 19 patients therapeutically anticoagulated with enoxaparin preoperatively demonstrated the likelihood of residual anti-factor Xa activity, even if the 24-hour interval is maintained. 106 Eleven of 19 patients still had anti-factor Xa activity that would place them at or above the lower limit for the peak target therapeutic range for VTE prophylaxis. One of these patients had an anti-factor Xa level within the target therapeutic range for thrombosis treatment.…”

“…108 However, recent reviews have suggested that a reduction in LMWH dose should be made even with CrCl between 30 and 50 mL/min because of the bleeding risk. 107 It is also interesting that many of the patients in the series by Henshaw et al, 106 for example, an 85-year-old, 53-kg woman with a calculated CrCl of 45 mL/min, received 60 mg BID. Her anti-factor Xa activity was 0.54 international unit (IU)/mL-still within treatment therapeutic peak target range of 0.5 to 0.8 IU/mL.…”

Regional anaesthesia in patients on antithrombotic drugs

“…If deciding to monitor LMWH anti-Xa activity before a neuraxial procedure, it is generally accepted to proceed with a level of 0.1 or less. 63 With regard to fondaparinux, German S1-Guidelines suggest that, where neuraxial block is indicated, an anti-Xa activity of 0.1 IU ml À1 or less should be targeted. 150 In patients on fondaparinux wherein there may be a risk of elevated plasma anti-Xa levels, if anti-Xa activity can be monitored, an activity value of 0.1 IU ml À1 or less can be considered a nondetectable anticoagulant effect.…”