Official Journal of the Society of Hospital Pharmacists of Australia

BRIEF REPORT

Enoxaparin for thromboprophylaxis in overweight and obese

patients: a prescribing audit at a tertiary hospital
Maryam Sherkat Masoum, BPharm(Hons), MClinPharm1 , Lynne M. Emmerton, BPharm(Hons),
PhD2,*
1 Department of Pharmacy, Royal Perth Hospital, Perth, Australia
2 School of Pharmacy and Biomedical Sciences, Curtin University, Perth, Australia

Abstract
Obesity increases the risk of venous thromboembolism (VTE). Literature is inconclusive regarding fixed or weight-based dose adjustment
of enoxaparin to prevent VTE in overweight and obese patients. Data were collected for all adult patients who received enoxaparin in
one of three wards at Royal Perth Hospital from September to December 2016. The reference dose for non-obese patients was 40 mg
daily. The key outcome was the percentage of obese patients (body mass index (BMI) ≥ 30 kg/m2) receiving dose-adjusted enoxaparin.
Of the 343 patients who received enoxaparin, 92 (27%) were obese and 108 (32%) overweight. Of 141 patients of ‘normal’ BMI, 127
(90%) received appropriate doses. Two obese patients received adjusted enoxaparin doses: 60 mg daily for 6 days, and 40 mg twice
daily before titration. Weight-based enoxaparin dosing was not prevalent in this sample of 92 obese patients. Local prescribing guide-
lines are warranted, and their effect should be monitored.

Keywords: enoxaparin, overweight, obesity, drug utilization review, venous thromboembolism, prescribing patterns, practice guideline.

INTRODUCTION dosing. At the Royal Perth Hospital (RPH) campus, a

Obesity is a significant risk factor for the development
of venous thromboembolism (VTE) in hospitalised
patients.1 Standard doses of 40 mg daily enoxaparin, a
low molecular weight heparin, are recommended for
VTE prophylaxis in patients with normal renal function
and body weight.2
In overweight patients, weight-based enoxaparin dos-
ing, using total body weight, has been reported as effec-
tive at once-daily doses of 0.4 and 0.5 mg/kg,1,3 as well as
with doses of 0.5 mg/kg every 12 h.4,5 In patients with a
body mass index (BMI) ≥30 kg/m2, fixed-dose regimens
of 40 mg enoxaparin twice daily have been shown to be
effective.6–8 However, one study reported 60 mg enoxa-
parin daily as superior to 40 mg enoxaparin twice daily,9
and another study reported that 60 mg enoxaparin twice
daily was superior to 40 mg enoxaparin twice daily.10
Although these findings support dose adjustment of
enoxaparin for thromboprophylaxis in obesity, there is
no consensus regarding fixed-dose or weight-based
*Address for correspondence: Lynne M. Emmerton, School of
Pharmacy and Biomedical Sciences, Curtin University, GPO Box
U1987, Perth, Western Australia 6845, Australia.
E-mail: lynne.emmerton@curtin.edu.au
450-bed tertiary adult public hospital in Western Aus-
tralia, the need for definitive prescribing guidelines for
overweight patients has been recognised, which war-
rants insight into current prescribing patterns. The aim
of this study is to describe prescribing patterns for
enoxaparin at the RPH in the absence of specific pre-
scribing guidelines for overweight or obese patients.
METHODS
The present study was a retrospective observational audit
of inpatient medication charts and medical notes, refer-
enced to available literature and the state-wide anticoagu-
lation recommendations, and aligned with the hospital’s
commitment to quality improvement and drug utilisation
review. Three wards (Orthopaedic Surgery, General Medi-
cine and the State Major Trauma Unit) were selected to
represent surgical, medical and critical inpatients.
The audit included patients of all body weights to
obtain data around weight- or BMI-related prescribing
decisions. Patients without available medical records,
documented weight, height or BMI, and patients receiv-
ing therapeutic, rather than prophylactic, anticoagula-
tion therapy were excluded from the audit.

Journal of Pharmacy Practice and Research (2019) 49, 376–379

© 2019 The Society of Hospital Pharmacists of Australia doi: 10.1002/jppr.1524
Enoxaparin in overweight and obese patients
Hardcopy chart review was undertaken for each
patient admitted to the study wards from 1 September
to 31 December 2016. Based on ward occupancy, the
sampling time frame, an estimated prevalence of over-
weight or obesity of 50% and an estimated prescribing
rate of prophylactic enoxaparin of 40%, we anticipated
476 cases of overweight/obese patients would be sam-
pled, with around 190 receiving enoxaparin prophylaxis.
This was considered adequate for descriptive compar-
isons. Data collected included patient characteristics,
clinical parameters (serum creatinine and sample collec-
tion times), VTE prophylaxis, initial enoxaparin dosage,
administration times and dose adjustments.
To identify patients with normal and impaired renal
function, the Cockcroft–Gault equation was used to esti-
mate creatinine clearance (CrCl). This calculation used
the more conservative (lower) of two values: total and
ideal body weight. Renal impairment warranting enoxa-
parin dose reduction was defined as CrCl < 30 mL/
min.2 BMI categories for reporting of enoxaparin pre-
scribing were as follows: obese (BMI ≥ 30 kg/m2), over-
weight (BMI 25.0–29.9 kg/m2) and normal weight (BMI
18.5–24.9 kg/m2). The reference dose for patients of nor-
mal weight and renal function was 40 mg/day,2 in the
absence of a definitive guideline for dose adjustment in
obesity. Analysis was descriptive and exploratory. Cate-
gorical variables are stated as numbers with percent-
ages, and continuous variables are reported as the
mean  SD.
This study was granted Quality Activity approval
(no. 13761) from the RPH Service 4 Safety and Quality
Committee (Tier 3), and was endorsed by the Curtin
University Human Research Ethics Committee (No.
11858).
RESULTS
Patient Characteristics
The 1047 admissions comprised 216 from Orthopaedic
Surgery, 43 from General Medicine, 429 from the State
Major Trauma Unit and 359 patients admitted to the
study wards under other specialties. Excluding 17%
(178/1047) with incomplete data, 869 admissions were
analysed for the prescribing of VTE prophylaxis. Of
these, 39.5% (343/869) received VTE prophylaxis with
enoxaparin, 38% (331/869) received unfractionated hep-
arin, 1.5% (13/869) received therapeutic anticoagulation
and 21% (182/869) did not receive prophylaxis. Of the
343 patients prescribed prophylactic enoxaparin, 58%
(200/343) were overweight or obese (Table 1). Of the 92
obese patients, 54 (58.7%) were male and 21 (22.8%)
weighed more than 150 kg.
© 2019 The Society of Hospital Pharmacists of Australia
377
Enoxaparin Prescribing in Relation to BMI and
Renal Function
Of the 326 patients prescribed enoxaparin and with
available CrCl data, the regimens were 40 mg daily
(95.7%; n = 312), 20 mg daily (3.7%; n = 12), 40 mg
twice daily (0.3%; n = 1) or 60 mg daily (0.3%; n = 1;
Table 2). Some underdosing of enoxaparin (20 mg/day)
was observed among patients with normal renal func-
tion, for whom a 40-mg/day dose would be warranted.
Based on CrCl, dose reduction was warranted for 15
patients. Four (including one of the four obese patients)
received 20 mg enoxaparin daily, as per guidelines for
non-obese patients; the remaining 11 received the stan-
dard 40-mg daily dose.2
Nearly all normal weight patients (127/141) received
an appropriate dose according to their renal function.
Of the remaining 14 patients, six received lower-
than-recommended doses and eight received 20 mg
enoxaparin daily in the absence of renal impairment.
Dose Adjustments in Obesity
The vast majority of obese patients with CrCl data (82/
85) received the standard dose of 40 mg/day (Table 2).
Enoxaparin dosing was increased for two of the 92
patients with a BMI ≥30 kg/m2; these two cases are
described below.
Case 1
A 62-year-old female with normal renal function and
BMI 36 kg/m2 was admitted for management of sepsis,
and received 60 mg enoxaparin daily. The patient died
as a result of worsening sepsis, at which point five daily
doses of enoxaparin had been administered.
Table 1 Patient characteristics (n = 343)
Age (years) 50  22
Male sex 200 (58)
BMI (kg/m2) 26.5  5.9
Normal weighta 143 (41.7)
Overweighta 108 (31.5)
Obesea 92 (26.8)
Weight (kg) 81.3  24.4
Severe renal impairment 6 (1.7%)
Length of hospital stay (days) 8.9  7.3
Duration of enoxaparin administration (days) 5.6  3.9
Data are given as the mean  SD or as n (%).
a
Normal weight was defined as body mass index (BMI) 18.5–
24.9 kg/m2, overweight was defined as BMI 25.0–29.9 kg/m2 and
obesity was defined as BMI ≥ 30 kg/m2.
Journal of Pharmacy Practice and Research (2019) 49, 376–379
378
Table 2 Enoxaparin dose in relation to body mass index and according to renal impairmenta
Enoxaparin dosing
20 mg q.d. 40 mg q.d.
CrCl (mL/min) <30 ≥30 <30 ≥30
BMIb (kg/m2)
18–25 3 6 8 124
25–30 – 2 0 98
≥30 1 0 3 79
Total 4 8 11 301
Data show the number of subjects in each group. N/A, serum creatinine was not measured.
a
Severe renal impairment was defined as creatinine clearance (CrCl) <30 mL/min.
b
Body mass index (BMI) 18.5–24.9 kg/m2 was considered normal weight, BMI 25.0–29.9 kg/m2 was considered overweight, and BMI ≥
30 kg/m2 was considered obese.
Case 2
A 27-year-old male (BMI 36 kg/m2) with normal renal
function, admitted with a fractured femur, initially
received enoxaparin 40 mg daily. Following consultation
with Haematology, the dose was increased after Day 2
(three doses) to 40 mg in the morning and 60 mg at
night, and the discharge plan indicated 6 weeks of VTE
prophylaxis with review. Outpatient notes, including a
review at 2 months after discharge, did not report the
ongoing enoxaparin dose and duration. This was the
only case of consultation with a haematologist regarding
dose selection, and the only case in which anti-Xa levels
were documented.
DISCUSSION
This audit provides an insight into the complexity and
uncertainty of dose adjustment of prophylactic enoxa-
parin, with specific focus on overweight/obesity, and
considering renal function. Although practices are exp-
ected to differ between hospitals, the findings of this
study have highlighted conservative dosing in the
absence of prescribing guidelines for the population of
concern. These insights inform the clinical setting in the
determination of local prescribing guidelines. Enoxa-
parin dosing was assessed in 343 inpatients, of whom
31% were overweight and 27% were obese. Analysis
revealed only two cases of enoxaparin dose increases
among the 92 obese patients, and little individualised
dosing overall. Most patients, regardless of weight or
BMI, received standard 40-mg/day doses. Given that
over 50% of patients were overweight or obese with
normal renal function, this finding suggests underdosing
of enoxaparin prophylaxis, when reflecting on the body
Journal of Pharmacy Practice and Research (2019) 49, 376–379
M. Sherkat Masoum and L. M. Emmerton
60 mg q.d. 40 mg b.i.d. Total
N/A <30 >30 <30 >30
2 – – – – 143
8 – – – – 108
7 – 1 – 1 92
17 – 1 – 1 343
of literature recommending dose adjustment in over-
weight and obese patients.1,3–9
Possible contributing factors include lack of aware-
ness of: (1) the need for dose adjustment of enoxaparin
thromboprophylaxis in overweight and obese patients;
and (2) the associated increased risk of VTE events. Lack
of local hospital guidelines for dose adjustment in obe-
sity, a third likely contributor, is now being addressed.
Current local anticoagulation guidelines derived from
the Australian Medicines Handbook recommend standard
enoxaparin doses of 40 mg daily, with dose reduction to
20 mg daily in severe renal impairment.2 State-wide
dedicated anticoagulation charts advise prescribers to
contact a haematologist regarding dosing in patients
weighing >150 kg. In this audit, a haematologist was
consulted in one case. A reminder is recommended for
inclusion in prescribing guidelines. The presence of
additional risk factors (recent surgery and/or trauma)
increases the risk of VTE in non-medical patients, and
warrants consideration in prescribing guidelines.
The present study had several limitations. The sample
was restricted to patients who received enoxaparin for
VTE prophylaxis in three wards of a single hospital,
and was time limited by ongoing activity around the
introduction of prescribing guidelines. General Medical
patients may have been underrepresented due to
reduced accessibility of their records. Although 343
cases of prophylactic enoxaparin prescribing were
sourced and enabled descriptive analysis, the study was
not designed to report clinical outcomes (VTE or bleed-
ing events during admission or after discharge) or surro-
gate clinical outcomes (anti-Xa monitoring, an indicator
of anticoagulation). Documentation of patients’ weight
and height was inconsistent, and requires addressing,
particularly when dose adjustments for weight, BMI or
© 2019 The Society of Hospital Pharmacists of Australia
Enoxaparin in overweight and obese patients
renal function are warranted. However, measurement of
weight is challenging in immobile patients.
This study suggests the need for hospital-wide audit
of VTE prophylaxis to establish a longitudinal database
or point-in-time analyses, including clinical outcomes
for patients, followed by derivation, implementation
and monitoring of a local prescribing guideline that
attempts to draw together the best-available evidence.
The key finding is that patient weight appears insuffi-
ciently considered in the prescribing of prophylactic
enoxaparin at the RPH, likely due to inadequate
awareness of evidence regarding enoxaparin thrombo-
prophylaxis in obesity. Comparison of the present find-
ings with a review of prescribing patterns after the
implementation of new guidelines may provide valu-
able information regarding the uptake and clinical
effect of the guidelines. The present methods may be
used in other jurisdictions facing a similar lack of clar-
ity in their prescribing guidelines. If prescribing of
enoxaparin in obese patients in other hospitals is iden-
tified as less conservative, perhaps with higher rates of
anti-Xa monitoring, those findings would warrant dis-
semination to other sites to assist in the evolution of
clinical practice.
ACKNOWLEDGEMENTS
The authors acknowledge RPH Medical Records staff
and Michael Leahy for assistance with data acquisition.
This study did not receive any specific funding.
Conflicts of Interest
MSM is employed as a clinical pharmacist at the study
hospital. MSM had not provided services to the study
patients or wards during the data collection.
© 2019 The Society of Hospital Pharmacists of Australia
379
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Received: 29 August 2018
Revised version received: 29 October 2018
Accepted: 09 November 2018
Journal of Pharmacy Practice and Research (2019) 49, 376–379