Analysis of Enoxaparin Dose Titration at a Large, Tertiary Teaching Facility

Background:

Enoxaparin, a low‐molecular weight heparin (LMWH), is frequently used in place of unfractionated heparin (UFH) for anticoagulation. LMWH have been favored by expert groups in many clinical settings given their advantages over UFH, including more predictable pharmacokinetics, greater ease of administration, better safety margin, possible improved efficacy and lack of need for therapeutic drug monitoring. In some cases, however, therapeutic drug monitoring using anti‐factor Xa levels (AXAL) is warranted. Several small case series of patients with renal insufficiency, morbid obesity, or solid organ transplant have shown that AXAL are on average greater than would be expected by weight‐based dosing. Additional research is needed to determine the most effective and safest dosing strategy for LMWHs in these patients.

Methods:

This is a retrospective cohort study at a large tertiary referral center, and the requirement for informed consent was waived by the institution. Patients hospitalized between Jan 1, 2006 and Apr 31, 2012 with an enoxaparin order plus at least two AXAL drawn within 30 days were included. Reasons for exclusion included missing height or weight data, receipt of less than 3 doses of enoxaparin corresponding to AXAL monitoring, using enoxaparin for prevention of VTE rather than treatment, and inability to interpret AXAL values based on charting.

Patients were analyzed according to whether or not a goal AXAL was reached during the study, and what if any dose adjustment was needed to achieve goal. Factors such as renal function, age, weight, dosing strategy, and other medical co‐morbidities were also examined. Definitions used in this study include the following: steady‐state AXAL= At least 3 doses of enoxaparin provided, peak AXAL= 3‐5 hours after a dose charted as given, and goal AXAL at steady state of 0.6‐1 units/mL for twice daily dosing and 1‐2 units/mL for once daily dosing.

Results:

Final analysis included 87 patients who met inclusion criteria, though 19 did not have a subsequent AXAL drawn at the proper time. The initial AXAL was at goal in 27 patients (31%). 31 patients (35%) had an initial AXAL above goal, 13 of whom later reached goal with a median dose decrease of 24%. 29 patients (33%) had an initial AXAL below goal; 11 of these later reached goal with a median dose increase of 16%. Ultimately 54 patients (62%) achieved a goal AXAL during the study. Though not statistically significant, patients with AXAL below goal tended to be younger, weigh less, and have a higher creatinine clearance than those with AXAL at or above goal.

Conclusions:

Our study shows that AXAL monitoring can be used to guide enoxaparin titration and that a dose increase or decrease of approximately 20% is an appropriate starting point in patients below or above goal AXAL, respectively. The vast majority of patients in the study had relatively normal body weight and renal function, and enoxaparin was initially dosed appropriately for weight in at least 76% of patients. Despite this, only 31% of patients had an initial therapeutic AXAL, suggesting that enoxaparin pharmacokinetics may not be as predictable as once thought.

Further areas of research include a larger, prospective study to design a dosing nomogram for clinicians desiring to use LMWH in conjunction with AXAL monitoring, especially in patients with renal failure or at extremes of weight. Also, the risk of bleeding and thrombosis in patients receiving LMHW should be assessed in relation to AXAL given the surprisingly low percentage of goal AXAL seen in this study.