Lack of anti-factor Xa assay standardization results in significant low molecular weight heparin (enoxaparin) dose variation in neonates and children

Introduction: Enoxaparin is a frequently used anticoagulant in children. Unlike in adults, consensus guidelines recommend therapeutic monitoring to a target anti-factor Xa level of 0.5-1 U mL^-1. Therapeutic ranges are not well correlated with clinical outcomes (e.g. thrombosis or hemorrhage), and assays are not standardized. Owing to limited reagent supplies, our clinical laboratory conducted a validation process and switched anti-FXa assays. Although the assays correlated well with each other, anti-FXa values were, on average, 33% higher with the new assay. The target anti-FXa range was not altered. We evaluated how this change in anti-FXa assays influenced enoxaparin dosing (mg kg^-1). Methods: Enoxaparin dosing and anti-FXa values for all patients started on enoxaparin for the 6 months before and after assay change were retrospectively compiled and analyzed with a Student's t-test. Results: One hundred and nine children were started on enoxaparin before assay change, and 104 after assay change. The mean therapeutic enoxaparin dose (mg kg^-1) was significantly lower in subjects aged < 3 months (P = 0.01) and 3 months to 2 years (P < 0.0001), but not in subjects aged > 2 years (P = 0.18), after assay change. The median number of enoxaparin dose changes required to achieve the target range was significantly reduced after assay change, from 1 to 0 (P = 0.004). Conclusions: The current pediatric practice of dose adjustment to achieve and maintain a target anti-FXa range is vulnerable to assay determination, which may provide false reassurance of efficacy and safety and represent misappropriation of time and resources. These data support a pediatric randomized controlled clinical trial comparing the safety and efficacy of enoxaparin weight-based dosing with or without dose titration based on anti-FXa.