Association of Outcomes and Anti-Xa Monitoring in Treatment of Pediatric Venous Thromboembolism

BACKGROUND/INTRODUCTION: With the increased use of venous catheters and improved survival from previously life-threatening pediatric disorders (e.g., congenital heart disease, cancer), the incidence of venous thromboembolism and the need for anticoagulation have also increased.  While unfractionated heparin and warfarin were once considered the standards of care, enoxaparin has now become the drug of choice in many pediatric institutions, given improved efficacy, fewer bleeding complications, minimal interaction with concurrent medications, and a more favorable pharmacokinetic profile.

Regular monitoring of Anti-Xa activity is generally recommended in children treated with enoxaparin. Though the published therapeutic range for Anti-Xa levels is 0.5 - 1.0 unit/mL, there is little data in the pediatric population regarding the outcomes associated with maintaining Anti-Xa levels at the higher versus lower end of the therapeutic range.

OBJECTIVES: The purpose of this study was to determine whether there was a difference in diagnostic outcomes when children received enoxaparin with Anti-Xa levels between 0.5 - 0.79 unit/mL (low therapeutic range) versus between 0.8 – 1.0 unit/mL (high therapeutic range) throughout their course of their treatment.

METHODS: Using the TCH DVT Registry, we retrospectively identified 107 subjects diagnosed with uncomplicated VTE and treated with enoxaparin.  Demographic information, Anti-Xa levels, dose modifications, and diagnostic outcomes were abstracted using the electronic medical record (Epic®) and analyzed.

RESULTS: We evaluated 103 patients with therapeutic Anti-Xa levels at the time of hospital discharge, of whom 93 had outcomes data. Of these 93 subjects, 38% (N = 35) had complete resolution after 3 months of therapy, 40% (N = 37) had partial resolution, 20% (N = 19) were unchanged, and 2% (N = 2) had progression of their initial thrombus. Of the 72 patients with any response to therapy (complete or partial resolution), 68% (N = 49) had a mean Anti-Xa level in the low therapeutic range and 32% (N = 23) had a mean Anti-Xa level in the high therapeutic range. In comparison, of the 21 patients with no documented response to therapy (unchanged or progression), 67% (N = 14) had a mean Anti-Xa level in the low therapeutic range, and 33% (N = 7) had a mean Anti-Xa level in the high therapeutic range.

Of the 93 subjects with outcomes data, all but one had a mean Anti-Xa level within the therapeutic range throughout their treatment course. Of these 92 patients, 68% (N = 63) had mean Anti-Xa levels in the low therapeutic range. 78% (N = 49) had any response (complete or partial resolution) after 3 months of therapy, and 22% (N = 14) had no documented response to therapy (unchanged or progression).  Of the 92 patients, 32% (N = 29) had mean Anti-Xa levels in the high therapeutic range. 76% (N = 22) had any response to therapy and 24% (N = 7) had no response to therapy.

CONCLUSIONS: There does not appear to be a statistically significant difference between low versus high range mean therapeutic Anti-Xa levels and the incidence of thrombus resolution. Empiric clinical practices of targeting Anti-Xa levels in the high end of the therapeutic range may not be warranted.