IV Versus Subcutaneous Enoxaparin in Critically

Ill Infants and Children: Comparison of Dosing,

Anticoagulation Quality, Efficacy, and Safety
Outcomes
Yaser A. Diab, MD; Karthik Ramakrishnan, MD; Brandon Ferrell, BS; Reginald Chounoune, BS, MS;
Fahad A. Alfares, MD; Kendal M. Endicott, MD; Sara Rooney, PharmD; Jason Corcoran, PharmD;
David Zurakowski, PhD; John T. Berger, MD; Venkat Shankar, MD; Dilip S. Nath, MD

Objective: Subcutaneous enoxaparin is the mainstay anticoagu-
lant in critically ill pediatric patients although it poses several chal-
lenges in this patient population. Enoxaparin infused IV over 30
minutes represents an attractive alternative, but there is limited
experience with this route of administration in children. In this
study, we assess dosing, anticoagulation quality, safety, and clini-
cal efficacy of IV enoxaparin compared to subcutaneous enoxapa-
rin in critically ill infants and children.
Design: Retrospective single-center study comparing dosing,
anticoagulation quality, safety, and clinical efficacy of two dif-
ferent routes of enoxaparin administration (IV vs subcutane-
ous) in critically ill infants and children. Key outcome measures
included dose needed to achieve target antifactor Xa levels,
time required to achieve target antifactor Xa levels, proportion
of patients achieving target anticoagulation levels on initial dos-
ing, number of dose adjustments, duration spent in the target
antifactor Xa range, anticoagulation-related bleeding complica-
tions, anticoagulation failure, and radiologic response to anti-
Interventions: One hundred ten patients were identified who had
received IV or subcutaneous enoxaparin and had at least one
postadministration peak antifactor Xa level documented.
Measurements and Main Results: Of the 139 courses of enoxa-
parin administered, 96 were therapeutic dose courses (40 IV and
56 subcutaneous) and 43 were prophylactic dose courses (20 IV
and 23 subcutaneous). Dosing, anticoagulation quality measure-
ments, safety, and clinical efficacy were not significantly different
between the two groups.
Conclusions: Our study suggests that anticoagulation with IV
enoxaparin infused over 30 minutes is a safe and an equally effec-
tive alternative to subcutaneous enoxaparin in critically ill infants
and children. (Pediatr Crit Care Med 2017; XX:00–00)
Key Words: antifactor Xa; enoxaparin; low molecular weight
heparins; pharmacodynamics; pharmacokinetics

coagulation.
Setting: Tertiary care pediatric hospital.
Patients: All children admitted to the cardiac ICU, PICU, or neo-
natal ICU who were prescribed enoxaparin between January
2014 and March 2016 were studied.
All authors: Children’s National Health System, Washington, DC.
Dr. Rooney disclosed off-label product use (enoxaparin is Food and Drug
Administration [FDA] approved for subcutaneous administration. The
article discusses a novel route of administration, IV. This is not an FDA-
approved route). Dr. Corcoran received funding from Silvergate Pharma-
ceuticals (one-time payment for participation in a clinical roundtable about
oral liquid medications [October 2014]). Dr. Berger’s institution received
funding from the National Institutes of Health and Association of Pediatric
Pulmonary Hypertension. The remaining authors have disclosed that they
do not have any potential conflicts of interest.
For information regarding this article, E-mail: dnath@childrensnational.org
Copyright © 2017 by the Society of Critical Care Medicine and the World
Federation of Pediatric Intensive and Critical Care Societies
DOI: 10.1097/PCC.0000000000001126
C
ritically ill neonates and children, especially those with
cardiac disease, are at increased risk for thromboembo-
lism (1, 2). As a result, anticoagulation for prevention
or treatment of thromboembolism is frequently administered
to this patient population (3). Unfractionated heparin and the
low molecular weight heparin (LMWH), enoxaparin, are the
two agents most commonly used for parenteral anticoagula-
tion in critically ill pediatric patients (3). Many prefer enoxa-
parin as the initial option due to better predictability of the
anticoagulant effect, reduced monitoring need, and reduced
risk of heparin-induced thrombocytopenia (4, 5). Enoxaparin
is also cleared more slowly than other LMWH anticoagulants
with a relatively longer apparent half-life, which leads to a sus-
tained anticoagulant effect after administration (4, 5).
Enoxaparin is approved for IV bolus administration in adult
patients with acute coronary syndromes (6–8); however, enoxa-
parin administered as a bolus IV results in more rapid peak levels
and faster clearance leading to significantly shortened half-life

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 Diab et al
(9, 10). There is limited pediatric experience with this route of
administration (10–12). Recently, enoxaparin given as a 30-min-
ute IV infusion every 12 hours in a small number of critically
ill pediatric patients was shown to achieve peak antifactor Xa
(anti-FXa) levels similar to subcutaneous (SC) dosing suggest-
ing that this route of administration may be a feasible option for
parenteral anticoagulation in critically ill neonates and children
(11). Although this administration route represents an attractive
option for parenteral anticoagulation in critically ill infants and
children, there are limited data regarding efficacy and safety of
this dosing strategy.
In 2014, we implemented an institutional protocol for IV
enoxaparin administered as a 30-minute infusion in critically
ill infants and children. We conducted a retrospective study to
compare dosing, anticoagulation quality, safety, and efficacy of
IV versus SC enoxaparin.
MATERIALS AND METHODS
Study Design and Population
The Institutional Review Board of the Children’s National
Health System (CNHS) approved this study with waiver of
informed consent. Patients were identified using CNHS
pharmacy database (Cerner PowerChart; Cerner Corpora-
tion, Kansas City, MO). All children admitted to cardiac ICU,
PICU, or neonatal ICU at the CNHS who received enoxa-
parin between January 2014 and March 2016 were screened
for inclusion. Patients who received SC or IV enoxaparin for
treatment or for prevention of thromboembolism and had
at least one anti-FXa level during the admission formed the
cohort for this analysis.
Enoxaparin Dosing Protocol
Patients included in this study received adjusted-dose twice daily
SC enoxaparin (administered directly without a SC catheter) or
IV enoxaparin infused over 30 minutes according to our institu-
tional protocol. Enoxaparin dosing and laboratory monitoring
protocols are extrapolated from adult data and are based on anti-
FXa levels (13). The starting doses for infants less than 2 months
old were 1.8 mg/kg/dose for target anti-FXa of 0.5–1 U/mL (ther-
apeutic dose) and 0.75 mg/kg/dose for target anti-FXa level of
0.1–3 U/mL (prophylactic dose). For children 2 months old and
older, the respective starting doses were 1 mg/kg/dose and 0.5 mg/
kg/dose. Anti-FXa levels were drawn 4–6 hours (timed from the
start of the infusion in children who received IV enoxaparin)
after patient had received at least two initial or adjusted doses.
Anti-FXa levels were measured in-house using a chromogenic
heparin-calibrated anti-FXa activity assay (STA-Liquid Anti-Xa;
Stago, Asnières-sur-Seine, France) on the STA-R Evolution ana-
lyzer (Diagnostica Stago, Parsippany, NJ). The STA-Liquid Anti-
Xa assay kit contains no exogenous antithrombin or dextran
sulfate. Dose adjustments were made according to a standard
nomogram (13). The administration route (IV vs SC), starting
dose, and dose adjustments were determined at the discretion of
the treating ICU physicians in consultation with pharmacy and
the hospital inpatient thrombosis service.
2 www.pccmjournal.org XXX 2017 • Volume XX • Number XXX
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Data Collection
Relevant demographic, clinical, and laboratory data were col-
lected from electronic medical records in a Research Electronic
Data Capture (REDCap) database for analysis. The entire
cohort was divided into two groups. The first group included
patients who received therapeutic dose enoxaparin (target anti-
FXa of 0.5–1 U/mL). The second group comprised of patients
who received prophylactic dose enoxaparin (target anti-FXa
of 0.1–0.3 U/mL). Patients in the therapeutic enoxaparin dose
were further stratified according to age (≤ 3 and > 3 mo). This
age cutoff to define infants—with respect to enoxaparin dose
requirements—has been commonly employed (14, 15).
Outcome Measures
Dosing and anticoagulation quality measurements analyzed in
this study included starting dose, dose required to achieve tar-
get range of anti-FXa levels, first anti-FXa level, first anti-FXa
level within target range, time required to achieve target anti-
FXa levels, proportion of patients achieving target anticoagula-
tion levels on initial dosing, number of dose adjustments, and
duration spent in the target anti-FXa range.
Safety was assessed by determining the frequency of anti-
coagulation-related major bleeding and/or clinically relevant
nonmajor bleeding defined according to the International
Society on Thrombosis and Haemostasis criteria (16).
Clinical efficacy was evaluated by determining the frequency
of anticoagulation failure, defined as new thromboembolism,
thromboembolism progression, and/or thromboembolism recur-
rence, and by assessing radiologic response to anticoagulation on
follow-up imaging in patients with history of thromboembolism.
Statistical Analysis
Patients within the three groups were compared based on the
route of enoxaparin administration (IV vs SC). Continuous
variables are reported as median and interquartile range (IQR)
and compared using the Mann-Whitney U test. Categorical or
binary data are compared by Fisher exact test. Two-tailed val-
ues of p value less than 0.05 were considered statistically sig-
nificant. Analysis of the data was performed using IBM SPSS
Statistics (version 23.0; IBM, Armonk, NY).
RESULTS
From January 2014 to March 2016, 110 patients admitted to
the cardiac ICU, neonatal ICU, or PICU at CNHS received 139
courses of IV or SC enoxaparin and had at least one postadmin-
istration peak anti-FXa level documented. Of the 139 courses,
96 (40 IV enoxaparin courses and 56 SC enoxaparin courses)
were therapeutic with a target anti-FXa level of 0.5–1 U/mL, and
43 (23 IV enoxaparin courses and 20 SC enoxaparin courses)
were prophylactic with a target anti-FXa level of 0.1–0.3 U/mL.
The characteristics of the study population are summarized
in Tables 1–3. The baseline characteristics in the two cohorts
were largely similar; however, patients who received IV enoxa-
parin were overall younger in age with a lower baseline weight
than patients who received SC enoxaparin.
 Online Clinical Investigation

Overall, IV enoxaparin was comparable to SC enoxaparin
with regards to dosing, anticoagulation quality measurements,
safety, and efficacy in all three cohorts (Tables 1–3 and Figs. 1
and 2). Dosing requirements and anticoagulation quality mea-
surements in infants (≤ 3 mo) who received IV or SC thera-
peutic enoxaparin were not significantly different (Table 1
and Fig. 1A); however, the median first peak anti-FXa activ-
ity was higher with IV enoxaparin (0.51 [IQR, 0.21–0.60] U/
mL) compared to SC enoxaparin (0.36 [IQR, 0.20–0.47] U/
mL) with a trend toward significance (p = 0.07) (Fig. 2A).
The median time required to achieve target levels was also
shorter with IV enoxaparin (1.0 [IQR, 1.0–4.0] d) compared
to SC enoxaparin (3.0 [IQR, 1.0–5.0] d) with a trend toward
significance (p = 0.07) (Table 1). In patients with history of
thromboembolism, there were no demonstrable differences
in the radiologic response to systemic anticoagulation with
enoxaparin with similar rates of complete or partial thrombus
resolution (Table 1). There was only one identifiable antico-
agulation failure which occurred in the SC enoxaparin group,
and there was no significant difference in the rates of major
bleeding or clinically relevant nonmajor bleeding between IV
and SC enoxaparin (5% vs 10%, p = 1.00) (Table 1).
In older infants and children (> 3 mo) who received thera-
peutic dose enoxaparin, IV enoxaparin administration resulted
in a higher first peak anti-FXa level with a trend toward signifi-
cance (0.55 [IQR, 0.33–0.81] U/mL with IV enoxaparin vs 0.38
[IQR 0.26–0.51] U/mL with SC enoxaparin; p = 0.07) (Fig. 2B).
The median first peak anti-FXa level within the target (0.5–1
U/mL) was significantly higher with IV enoxaparin (0.67 [IQR,
0.61–0.79] U/mL) compared to SC enoxaparin (0.56 [IQR,
0.51–0.70 U/mL) (p = 0.024) (Fig. 2B). Otherwise, dosing and
anticoagulation quality measurements were not significantly
different between the two groups (Table 2 and Fig. 1B). The
frequency of bleeding events was similar in the IV enoxaparin

Comparison of Therapeutic Enoxaparin (Target Antifactor Xa Level, 0.5–1 U/mL)

Table 1.
According to Administration Route in Infants 3 Months Old or Younger
IV Enoxaparin (n = 20 Courses Subcutaneous Enoxaparin
Variable Given to 15 Patients) (n = 20 Courses Given to 16 Patients) p

Age (mo) 2 (1–3) 1.0 (0.1–3.0) 0.15

Weight (kg) 3.5 (2.4–4) 3.4 (3.2–4.5) 0.38
Male gender, n (%) 10 (66) 11 (69) 1.00
Cardiac disease, n (%) 11 (73) 12 (75) 1.00
Duration enoxaparin given (d) 22 (5.0–56.0) 20 (14–37) 0.99
Baseline platelet count (k/μL) 209 (151–316) 260 (188–357) 0.26
Baseline partial thromboplastin time (s) 37 (33–44) 39 (32–59) 0.65
Baseline international normalized ratio 1.24 (1.14–1.46) 1.31 (1.14–1.42) 0.61
Baseline antithrombin (%) 52 (37–74) 51 (36–55) 0.68
Baseline creatinine (mg/dL) 0.40 (0.30–0.50) 0.40 (0.36–0.50) 0.55
Time required to achieve target 1 (1–4) 3 (1–5)
anticoagulation levels (d) 0.07
Proportion of patients who achieved 11 (55) 8 (40)
target levels on initial dosing, n (%) 0.35
No. of dose adjustments 3 (1–6) 2 (0–3) 0.15
Dose adjustments per day of therapy 0.1 (0.1–0.3) 0.1 (0–0.2) 0.53
Time in the target range (d) 18.5 (4.0–37.5) 19.0 (6.5–30.5) 0.87
Percent time in the target range 79 (67–90) 77 (55–86) 0.46
Major or clinically relevant nonmajor 1 (5) 2 (10)
bleeding, n (%) 1.00
Radiologic response, n (%)
 Complete 7 (54) 5 (33)
0.65
 Partial 3 (23) 7 (47)
  No resolution 3 (23) 2 (13)
Anticoagulation failure, n (%) 0 (0) 1 (7) 1.00
Data are reported as median (interquartile range) or frequency (%) and analyzed using Mann-Whitney U test or Fisher exact test, as appropriate.

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 Diab et al

Table 2. Comparison of Therapeutic Enoxaparin (Target Antifactor Xa Level, 0.5–1 U/mL)

According to Administration Route in Infants and Children More than 3 Months Old
IV Enoxaparin (n = 20 Courses Subcutaneous Enoxaparin (n = 36
Variable Given to 17 Patients) Courses Given to 29 Patients) p

Age (mo) 8 (4–58) 23 (7–35) 0.34

Weight (kg) 7.4 (4.6–16.7) 12 (7–14.9) 0.21
Male gender, n (%) 11 (65) 19 (66) 1.00
Cardiac disease, n (%) 12 (71) 21 (72) 1.00
Duration enoxaparin given (d) 8 (5–28) 12 (7–27) 0.37
Baseline platelet count (k/μL) 233 (165–480) 275 (206–370) 0.75
Baseline partial thromboplastin time (s) 33 (29–41) 33 (31–40) 0.69
Baseline international normalized ratio 1.19 (1.07–1.31) 1.21 (1.07–1.40) 0.70
Baseline antithrombin (%) 60 (44–86) 76 (69–102) 0.05
Baseline creatinine (mg/dL) 0.50 (0.40–0.60) 0.40 (0.30–0.50) 0.16
Time required to achieve target anticoagulation 4 (2–23) 9 (4–19) 0.30
levels (d)
Proportion of patients who achieved target levels on 8 (40) 14 (39) 1.00
initial dosing, n (%)
No. of dose adjustments 3 (1–6) 2 (0–3) 0.15
Dose adjustments per day of therapy 2 (0–3) 1 (0–2) 0.89
Time in the target range (d) 4 (2–22.3) 9 (5–19) 0.23
Percent time in the target range 70 (45–99) 75 (60–93) 0.71
Major or clinically relevant nonmajor bleeding, n (%) 1 (5) 2 (6) 1.00
Radiologic response, n (%)
 Complete 7 (54) 14 (50)
 Partial 1 (8) 6 (21.5) 0.72
  No resolution 2 (15) 2 (7)
  No follow-up studies available 3 (23) 6 (21.5)
Anticoagulation failure, n (%) 0 (0) 0 (0) 1.00
Data are reported as median (interquartile range) or frequency (%) and analyzed using Mann-Whitney U test or Fisher exact test, as appropriate.

group (5%) and the SC enoxaparin group (6%) (p = 1.00) DISCUSSION

(Table 2). Similarly, there were no significant differences in the
radiologic response to therapeutic anticoagulation with enoxa-
parin with similar rates of thrombus resolution, and there were
no anticoagulation failures in either group (Table 2).
The dosing requirements and the overall anticoagulation
quality measurements in patients who received prophylactic
dose enoxaparin (target anti-FXa level of 0.1–0.3 U/mL) were
not significantly different between the two groups. Patients
who received prophylactic dose IV enoxaparin did however
require significantly more total dose adjustments, and there
was a trend toward a higher first peak anti-FXa level with SC
enoxaparin (Table 3 and Figs. 1C and 2C). The frequency of
bleeding events and anticoagulation failure was not signifi-
cantly different between the two groups (Table 3).
In this study, we report our center’s experience after imple-
mentation of a clinical protocol for IV enoxaparin as an alter-
native to SC enoxaparin in critically ill infants and children.
Our data suggest that enoxaparin administered as a 30-minute
infusion for treatment or prevention of thromboembolism in
critically ill pediatric patients is not significantly different from
SC enoxaparin with regards to dosing, quality of anticoagula-
tion, safety, or efficacy.
IV enoxaparin administration represents an attrac-
tive option to improve bioavailability in critically ill infants
and children as edema, peripheral vasoconstriction, and/or
decreased SC tissue in small infants can make achieving tar-
get concentrations using currently recommended SC dosing
challenging (17–20). Repeated SC injections also often result

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 Online Clinical Investigation

Table 3. Comparison of Prophylactic Enoxaparin (target Antifactor Xa level, 0.1–0.3 U/mL)

According to Administration Route
IV Enoxaparin (n = 23 Courses Subcutaneous Enoxaparin (n = 20
Variable Given to 17 Patients) Courses Given to 16 Patients) p

Age (mo) 7 (4–17) 12 (7–22) 0.15

Weight (kg) 6.8 (4–9.3) 8.5 (7.2–11.9) 0.14
Male gender, n (%) 7 (41) 8 (50) 0.73
Cardiac disease, n (%) 14 (82) 12 (75) 0.69
Duration enoxaparin given (d) 11 (8–32) 14 (7–28) 0.87
Baseline platelet count (103/μL) 304 (193–437) 262 (124–351) 0.29
Baseline partial thromboplastin time (s) 34 (33–42) 33 (32–36) 0.31
Baseline international normalized ratio 1.30 (1.16–1.52) 1.16 (1.04–1.39) 0.22
Baseline creatinine (mg/dL) 0.40 (0.30–0.60) 0.50 (0.40–0.60) 0.38
Time required to achieve target anticoagulation levels (d) 2 (1–5) 1.5 (1–3.5) 0.26
Proportion of patients who achieved target levels on initial 10 (44) 15 (75) 0.06
dosing, n (%)
No. of dose adjustments 2 (0.75–3) 2 (0–3) 0.012a
Dose adjustments per day of therapy 0.1 (0–0.2) 0 (0–0.1) 0.06
Time in the target range (d) 9.5 (5.75–29.25) 10.5 (3–24.5) 0.62
Percent time in the target range 80.5 (59–91.75) 71 (60–89.25) 0.63
Major or clinically relevant nonmajor bleeding, n (%) 1 (4) 0 (0) 1.00
Anticoagulation failure, n (%) 1 (4) 1 (5) 1.00
Statistically significant.
a

Data are reported as median (interquartile range) or frequency (%) and analyzed using Mann-Whitney U test or Fisher exact test, as appropriate.

in pain, bruising, hematomas, and distress to patients and their
families (21, 22). Although administration of enoxaparin using
an indwelling SC catheter (Insuflon; Unomedical A/S, Lejre,
Denmark) may reduce injection-site pain, significant local
adverse effects at the catheter insertion site have been reported
in infants (23). Furthermore, at our center, we have observed
significant variability in anti-FXa levels in infants receiving
enoxaparin via the Insuflon (Unomedical A/S) catheter.
Published pediatric experience with IV enoxaparin is lim-
ited (10–12). In a small case series of seven critically ill pediat-
ric patients, Crary et al (10) reported that enoxaparin given as
an IV bolus resulted in achieving peak anti-FXa levels at 1–2
hours followed by a substantial decrease 6–8 hours after an IV
dose suggesting that more frequent dosing may be necessary
with the IV route. This study also suggested that the dose of
IV enoxaparin required to achieve therapeutic levels may be
higher than the published doses with SC administration (10).
More recently, Cies et al (11) compared 15 critically ill pediatric
patients who received IV enoxaparin infused over 30 minutes to
control patients who received SC enoxaparin and showed that a
30-minute IV enoxaparin infusion produced therapeutic peak
anti-FXa levels similar to SC dosing with no adverse effects.
As reported in the study by Cies et al (11), we demonstrated
that IV enoxaparin infused over 30 minutes utilizing the same
weight- and age-based dosing algorithm for SC enoxaparin
achieved target peak anti-FXa level at doses that were not signifi-
cantly different suggesting similar pharmacodynamics. We also
observed an improved anticoagulation quality with the IV route
in patients who required therapeutic enoxaparin as evident by an
overall higher peak anti-FXa levels and shorter time to achieve
target levels suggesting that IV administration may lead to thera-
peutic anticoagulation faster and more reliably than SC dosing.
This difference is potentially clinically significant with respect to
provide effective anticoagulation in this critically ill patient popu-
lation. On the other hand, we found that in patients who received
prophylactic enoxaparin, there was a trend toward higher first
peak anti-FXa levels and an increased need for dose adjustments
with IV enoxaparin. This difference can be explained by the over-
all younger age of the IV group compared to SC group as infants
especially neonates require more dose changes to achieve the
target range (24, 25). Because of smaller sample size, we did not
stratify the prophylactic group by age as we did with the thera-
peutic group. More importantly, the clinical significance of this
difference is doubtful since all other outcome measures were
similar between the two administration routes.
The findings of this study also raise important clinical con-
siderations regarding current dosing strategy, efficacy, and safety
of anticoagulation with enoxaparin in the critically ill pediatric

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 Diab et al
patient population. We found that a significant proportion of
patients receiving IV or SC enoxaparin according to our insti-
tutional protocol did not achieve target levels on initial dosing,
and there was a delay in achieving target levels. This was most
noticeable in infants and children over 3 months old receiving
therapeutic enoxaparin. This is likely due to the fact that at our
center, enoxaparin was started in this cohort at the currently
suggested dose of 1 mg/kg while younger infants (< 2 mo old)
received an initial dose of 1.8 mg/kg, which was higher than the
recommended dose (1.5 mg/kg) (26). These findings are sup-
ported by a recent study by Schloemer et al (20) which showed
that only 42% of critically ill infants achieved target therapeutic
anti-FXa levels on initial dosing according to current enoxaparin
dosing guidelines for pediatric patients and that infants more
than 2 months old require a higher enoxaparin dose (1.3 mg/kg)
to achieve the target therapeutic range. Conversely, we found
that enoxaparin-administered IV or SC led to consistent antico-
agulation as measured by time in the target range with low rates
of thrombus nonresolution, anticoagulation failure, or bleeding
complications indicating that enoxaparin-administered IV or
SC was an effective anticoagulant with acceptable safety profile
in this high-risk patient population.
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Figure 1. Box plots of enoxaparin dose required to achieve target levels
in the overall patient cohort and in patients who achieved target levels on
initial dosing compared by administration route for therapeutic enoxaparin
in patients 3 mo old or younger (A), therapeutic enoxaparin in patients
greater than 3 mo old (B), and prophylactic enoxaparin (C). Groups
were compared by the Mann-Whitney U test (p < 0.05 was considered
significant). Box plot explanation: upper horizontal line of box, 75th
percentile; lower horizontal line of box, 25th percentile; horizontal bar
within box, median; upper horizontal bar outside box, 90th percentile; and
lower horizontal bar outside box, 10th percentile. SC = subcutaneous.
Our study represents the largest and most representative
pediatric experience to date with IV enoxaparin in critically
ill infants and children. We analyzed several well-defined
objective outcome measurements and provided important
real-world data; however, our study is limited by its retrospec-
tive single-center design. Although the largest study to date,
our sample size is overall still small, and larger prospective
randomized control trials are needed to further establish the
role of IV enoxaparin in the critically ill pediatric population.
Furthermore, anti-FXa levels were obtained per standard of
care at a single time point (4–6 hr after enoxaparin dose) so we
cannot ascertain that the pharmacokinetics and pharmacody-
namics of IV enoxaparin are similar to SC enoxaparin.
CONCLUSION
IV enoxaparin infused over 30 minutes appears to offer a safe
and effective option for parenteral anticoagulation in criti-
cally ill infants and children at risk for thromboembolism. The
results of this study support the need for a larger, multicenter
prospective study comparing IV with SC enoxaparin adminis-
tration for prevention and treatment of thromboembolism in
critically ill pediatric population.
 Online Clinical Investigation

Figure 2. Box plots of first antifactor Xa (anti-FXa) level and first

anti-FXa level within target range compared by administration route for
therapeutic enoxaparin in patients 3 mo old or younger (A), therapeutic
enoxaparin in patients greater than 3 mo old (B), and prophylactic
enoxaparin (C). Groups were compared by the Mann-Whitney U test
(p < 0.05 was considered significant). Box plot explanation: upper
horizontal line of box, 75th percentile; lower horizontal line of box,
25th percentile; horizontal bar within box, median; upper horizontal bar
outside box, 90th percentile; and lower horizontal bar outside box, 10th
percentile. SC = subcutaneous.

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