Impact of a Pharmacist Driven Anti-Xa Level Monitoring Protocol on Therapeutic Drug Monitoring Practice Patterns

Introduction:

Low molecular weight heparin (LMWH) has a favorable pharmacokinetic profile which precludes the need for routine laboratory monitoring. However, certain patient populations, including those with extreme body weight (overweight or underweight), renal dysfunction, history of bleeding event while receiving LMWH, or previous failure of therapy, may benefit from therapeutic monitoring. Suboptimal drug monitoring of enoxaparin due to incorrect timing of anti-Xa levels, delayed blood sample draws, and/or lack of follow up once the anti-Xa level has resulted has been documented in the literature and may lead to toxicity or suboptimal efficacy (Hosp Pharm. 2017 Mar; 52(3): 214-220.). A retrospective chart review conducted at our institution in 2015 evaluated 100 adult patients who were prescribed LMWH and were ordered an anti-Xa level over a ten month period. In 36% of patients, there was no documented indication for therapeutic monitoring of the LMWH. The study also demonstrated that 35% of anti-Xa levels were drawn outside of the recommended 3 to 5 hour time frame after the previous LMWH dose, and follow up action to abnormal levels was only performed for 39% of patients. In October 2018, our institution implemented a pharmacist driven protocol for anti-Xa level monitoring, including restriction of ordering of anti-Xa levels by a pharmacist, and recommendations for dose adjustments in response to non-therapeutic levels. The purpose of this analysis was to evaluate the impact of a pharmacist driven anti-Xa level monitoring protocol on compliance with institutional guidelines for LMWH monitoring, including indication for drug monitoring, timing of levels, and follow up to abnormal anti-Xa levels.

Methods:

We conducted a retrospective chart review of adult patients who received therapeutic enoxaparin and were ordered for an anti-Xa level between October 17, 2017 and July 1, 2018. Pediatric patients (<18 years of age) and patients receiving prophylactic enoxaparin were excluded. Levels were assessed for each patient encounter in patients who had more than one hospital admission during the study period, however only the first anti-Xa level on each admission was evaluated. Data analyzed included patient demographics, enoxaparin dose and indication, ordering service, presence of a Hematology consult, indication for anti-Xa level monitoring, timing of the level after previous enoxaparin dose, timing of sample collection by nursing staff, appropriate number of doses prior to level, appropriateness of follow up action to abnormal levels, bleeding events, and recurrent thrombosis.

Results:

During the study period, a total of 109 anti-Xa levels were ordered for 102 patients who met inclusion criteria. The most common indication for enoxaparin therapy was for venous thromboembolism (81%), followed by atrial fibrillation (9%). The most common indication for assessment of anti-Xa levels were for body weight ≥150 kg and/or BMI ≥40 kg/m² (28%), creatinine clearance <30 ml/min or renal replacement therapy (23%), and previous failure of anticoagulation (19%). Of the 109 anti-Xa levels assessed, 93% were ordered appropriately (3-5 hours post scheduled dose and after ≥3 doses of enoxaparin). Of the 97 total anti-Xa levels scheduled correctly, 87% were drawn at the appropriate time by nursing staff. Of the 57 levels that were not within the therapeutic range, 75% had a documented follow up facilitated by the pharmacist, which included a recommendation of follow up action.

Conclusion:

Appropriate monitoring of enoxaparin and correct timing of anti-Xa levels is crucial to facilitate proper clinical decision making and dose adjustments. Timely follow up to drug levels is also critical when the values are out of range, which may increase the risk of toxicity or decreased efficacy. The implementation of a pharmacist driven anti-Xa level protocol at our institution dramatically increased the number of correctly drawn anti-Xa levels, from 65% to 87% (p=0.00016). Follow up to non-therapeutic levels also increased significantly from 39% to 75% (p=0.0001) after implementation of the protocol. Further analysis and assessment of levels from a larger time period may be necessary to determine the clinical impact of implementation of a pharmacist driven anti-Xa monitoring protocol.