Introduction
A venous thromboembolism (VTE) is a blood clot that encompasses a deep vein thrombosis (DVT) or pulmonary embolism (PE), which leads to various signs, symptoms, and tissue destruction based on clot location. This usually occurs after injury to a vessel from central line insertion, trauma, surgery, and acute or chronic disease states that initiate the intrinsic or extrinsic coagulation cascade. Enoxaparin, a low molecular weight heparin, is considered the standard of care for VTE treatment in children due to greater predictability of kinetics and the ability to monitor levels.1 It works by binding to and accelerating antithrombin III activity and therefore inhibiting coagulation factor Xa and IIa. Through Xa inhibition, the conversion of prothrombin to thrombin is inhibited, which leads to the prevention of a fibrin clot formation. Venous thromboembolism treatment varies based on many factors such as age, weight, renal function, and treatment indication.
According to CDC data from 1994 and 2009, 78,685 pediatric patients were discharged with a VTE diagnosis, of which 3740 were associated with an in-hospital death.2 The annual incidence of VTE in children is 0.7 to 2.1 per 100,000 people and added an average cost of $25,000 per child per year.3 These costs may include but are not limited to; length of stay, diagnostic tests, treatment, hospitalizations, outpatient visits, and comorbidity management.4
Enoxaparin therapeutic monitoring for pediatric patients is accomplished through anti-Xa monitoring with a goal of 0.5 to 1.0 IU/mL. At our institution, this level is usually drawn on average of 4 hours (3-6 hours) after the second or third dose of a new dosing regimen. Traditionally in adult patients, anti-Xa monitoring is not routinely performed, mainly due to a potential of incorrectly drawing the levels and pharmacokinetic and pharmacodynamic stability in adult patients.5-7 Monitoring may prove to be beneficial in adults if they have renal dysfunction or obesity. Studies have yet to demonstrate a true correlation between therapeutic levels and enoxaparin efficacy or safety, especially in children.8-10 Hence, it is difficult to understand the full utility of monitoring of all children on enoxaparin therapy, which may lead to unnecessary health care costs.
The frequency of levels being drawn varies based on healthcare team’s comfort level, especially when a therapeutic value is obtained. Currently, the only source that directs the number of times a level is drawn after a therapeutic level is based off of expert opinion, which is published in the 2012 CHEST guideline.1,11 The recommendations are to check levels after starting a dose or dose change and once a correct dose is established based on the anti-Xa levels. It is then recommended to confirm using a repeat level, then check the following week and monthly once stable. The number of dose adjustments from the CHEST guideline initial dosing and dose adjustment guidelines have shown variability in adjustments in the pediatric population.12 To our knowledge, a study has not yet evaluated the characteristics that are associated with enoxaparin dose changes in pediatric patients. The objective of this study is to evaluate covariates in pediatric patients to determine which variables are most likely to be associated with enoxaparin dose changes, which will lead to more predictable anticoagulant management.