Evaluation of therapeutic anticoagulation with enoxaparin and associated anti-Xa monitoring in patients with morbid obesity: a case series

Abstract

Our purpose was to describe anti-Xa levels, dosage requirements, and complications associated with enoxaparin treatment doses in patients with morbid obesity. Inpatients with a BMI >40 kg/m(2) at an academic medical center prescribed therapeutic enoxaparin from 2004 to 2010 who also had an associated anti-Xa level were included in this retrospective evaluation. Twenty-six patients were identified having median weight of 162 kg (range 106-243), median BMI of 49.5 kg/m(2) (range 40.1-98.1), and median enoxaparin duration of 4 days (range 1-32). Venous thromboembolism was the most common reason for anticoagulation (n = 19, 73%). The median starting dose was 0.8 mg/kg actual body weight (range 0.51-1; absolute dose 80-150 mg) every 12 h. Twelve patients (46%) achieved a goal anti-Xa level, 10 (38%) were above goal and 4 (15%) were uninterpretable. Among the 10 patients with anti-Xa levels above goal, the median initial dose was 0.85 mg/kg (range 0.75-1) versus 0.74 mg/kg (range 0.51-1) for patients at goal with similar median peak serum creatinine (PSCr) values between these two groups (P > 0.05). No bleeding events occurred in patients achieving goal anticoagulation versus 4/10 (40%) with high anti-Xa levels (P = 0.033) with similar median PSCr between these groups. No thrombotic events occurred while on therapy. The majority in this cohort with morbid obesity achieved anti-Xa levels at or above goal at doses less than the recommended 1 mg/kg every 12 h. Bleeding events were more frequent among patients with anti-Xa levels above goal, despite similar PSCr values.

Evaluation and Pharmacokinetics of Treatment Dose Enoxaparin in Hospitalized Patients With Morbid Obesity

“…The mean antiXa levels for patients who bled and those who did not were 1.5 IU/mL and 0.95 IU/mL (P < .01), respectively. 10 Increased pharmacodynamic response to enoxaparin in obese patients is likely reflective of the drug's V d , which is roughly equivalent to plasma volume and reflects poor distribution into adipose tissue as well as altered pharmacokinetic parameters in obesity. [4][5][6][7][8] Adipose weight and lean mass disproportionately increase as ABW increases, with a decrease in the LBW to adipose tissue ratio with increased total weight.…”

“…[4][5][6][7][8] This pharmacokinetic characteristic may increase the antithrombotic activity of enoxaparin in extremely obese patients compared to nonobese patients with the risk of elevated antifactor Xa (anti-Xa) levels, which are associated with increased bleeding events. [9][10][11][12] The American College of Chest Physicians' guidelines and the College of American Pathologists recommend monitoring the antithrombotic effect of lowmolecular-weight heparins (LMWHs) in special populations, including patients with obesity, using the anti-Xa assay with a target peak therapeutic range of 0.6 to 1 IU/mL for twice-daily enoxaparin treatment dosing. 13,14 Clinical studies evaluated enoxaparin with weight-based or fixed dosage regimens, without prospective correlation of clinical outcomes with anti-Xa levels.…”

Monitoring Enoxaparin with Antifactor Xa Levels in Obese Patients

“…Changes in the pharmacokinetics of enoxaparin affected by obesity could also explain the elevated antifactor Xa levels. Obese patients have greater cardiac output and hepatic blood flow, as well as an increased glomerular filtration rate . These differences could increase the clearance of enoxaparin in obese patients compared with their normal weight counterparts .…”

“…Obese patients have greater cardiac output and hepatic blood flow, as well as an increased glomerular filtration rate. 18 These differences could increase the clearance of enoxaparin in obese patients compared with their normal weight counterparts. 19 It has been proposed that clearance of enoxaparin linearly increases with LBW, instead of TBW, in obese patients.…”

Clinical Feasibility of Monitoring Enoxaparin Anti-Xa Concentrations: Are We Getting it Right?

“…These patient characteristics include renal or hepatic insufficiency, extremes of body weight (≤ 40 kg or ≥150 kg), newborns, children, pregnancy, prolonged therapy (≥7-10 days), and advanced age. 8,[11][12][13][14][15][16][17] Furthermore, there are not strong data to support the use of anti-Xa monitoring in the majority of patients receiving enoxaparin outside of these select patient populations. Enoxaparin anti-Xa monitoring may be difficult and often incorrect in the clinical practice setting.…”