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.