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Lack of anti‐factor Xa assay standardization results in significant low molecular weight heparin (enoxaparin) dose variation in neonates and children
Author(s) -
Greene L. A.,
Law C.,
Jung M.,
Walton S.,
Ignjatovic V.,
Monagle P.,
Raffini L. J.
Publication year - 2014
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12641
Subject(s) - dosing , medicine , low molecular weight heparin , therapeutic index , heparin , thrombosis , anticoagulant , pharmacology , gastroenterology , drug
Summary 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.