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dose enoxaparin. Published literature regarding therapeutic
enoxaparin in morbidly obese individuals with VTE is also
reviewed.

Case Report
A 52-year-old African American, morbidly obese man
(height: 183 cm, weight: 236 kg, BMI: 68.2 kg/m2) presented
to the hospital with a chief complaint of left lower extremity
pain and shortness of breath with exertion. His past medical
history was significant for hypertension, bilateral lower
extremity lymphedema and chronic back pain. He stated his
lower extremity pain was a chronic issue that worsened with
exertion and his dyspnea had been occurring for 4 weeks and
was associated with orthopnea. Prior to admission, his medications included the following: aspirin 81 mg daily, atorvastatin 40 mg daily at bedtime, metoprolol tartrate 50 mg twice
a day, and duloxetine ER 60 mg daily.
On admission, his laboratory values included the following: sodium 134 mEq/L, potassium 3.5 mEq/L, blood urea
nitrogen 18 mg/dL, serum creatinine 1.96 mg/dL (baseline
1.1-1.3 mg/dL), glucose 228 mg/dL, and elevated d-dimer
8.84 mg/L FEU. Coagulation laboratory values at baseline
included the following: hemoglobin 13 g/dL, hematocrit
40.5%, platelets 234 × 103/µL, aPTT 24.2 seconds, PT 11.3
seconds, International normalized ratio (INR) 1.05. Vitals
demonstrated tachycardia (heart rate: 134 bpm), normal
respiratory rate (18 RR), blood pressure (135/83 mmHg),
and temperature (37.6°C). Ultrasound examination of the left
lower extremity was limited by edema; however, no thrombus was identified. A ventilation and perfusion scan performed for suspected PE was severely limited by body
habitus, but revealed low probability for PE in the areas that
were able to be visualized. CT scan was unable to be performed even after patient's renal function recovered to baseline due to his body habitus. The medical team deemed the
patient at moderate risk of PE given his clinical picture which
included ongoing tachycardia despite beta blockade, elevated d-dimer, and poor discriminative value of diagnostic
tests. An ankle brachial index was then performed on the
patient's left leg revealing a value of 0.0, indicating critical
limb ischemia. Angiography of the leg demonstrated complete lack of flow below the knee; however, the vascular surgeon recommended against thrombectomy and thrombolytics
given the patient's body habitus and clinical condition. The
decision was made to forego surgical intervention and pursue
systemic anticoagulation, which was already deemed necessary for suspected PE.
Intravenous heparin therapy titrated to a target PTT of
48-78 seconds based on institutional protocol was initiated
for both acute limb ischemia and suspected PE with concomitant warfarin until INR equaled or exceeded 2 on two consecutive days. On day 3 of warfarin therapy, the medical
team transitioned the patient from heparin to subcutaneous
(SQ) enoxaparin to expedite discharge to skilled nursing

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facility (Table 1). A weight-based dose of enoxaparin 0.83
mg/kg SQ Q12 hours was chosen based on previously published literature8 and rounded to 200 mg SQ Q12 hours based
on institutional policy, resulting in a dose of 0.85 mg/kg SQ
Q12 hours. Anti-Xa levels were ordered following the third
dose; however, due to an error anti-Xa levels were rescheduled and drawn 4 hours following the fifth dose of enoxaparin, which resulted in 1.01 IU/mL. The institutional target
therapeutic range for enoxaparin anti-Xa is 0.5-1 IU/mL.
Enoxaparin therapy of 200 mg SQ Q12 hours was continued.
The patient was discharged to a skilled nursing facility on
day 6 of warfarin therapy with an INR of 2.17, and with
improved lower extremity pain and swelling. He was discharged on his home medications plus warfarin 10 mg daily
and enoxaparin 200 mg SQ Q12 hours. On day 7 of warfarin
therapy, the INR value was 2.2. Enoxaparin therapy was discontinued since patient had achieved an INR ⩾ 2 on two
consecutive days. Of note, all other laboratory values including coagulation panel remained within normal limits, and
patient did not exhibit any signs or symptoms of bleeding
during therapy.

Discussion
This patient case adds to the growing amount of published
evidence demonstrating reduced weight-based doses of therapeutic enoxaparin may be necessary for the morbidly obese
population. The nonlinear increase in PD effects with
increasing body weight has a physiologic basis. Enoxaparin
is a hydrophilic molecule with a volume of distribution (Vd)
that roughly approximates plasma volume.6-8,13 Blood volume and total body water, however, do not increase linearly
with increasing body weight.14 Therefore, an argument for a
reduced dose requirement of enoxaparin could be made for
the morbidly obese population; however, there is limited PK
data to support this conclusion.
One PK/PD analysis compared 24 healthy obese patients
(BMI range: 29.6-48.4 kg/m2) and 25 normal weight individuals (BMI range: 19.4-25.5 kg/m2) who were administered 2 separate enoxaparin regimens separated by a 7-day
washout period: 1.5 mg/kg SQ once daily for 4 consecutive
days followed by 1.5 mg/kg IV infusion over 6 hours.7 In the
analysis of SQ enoxaparin, it was found that obese patients
took longer to reach steady state concentrations when compared to normal weight individuals and obese patients also
had higher exposure in terms of anti-Xa activity (14% higher
on day 1, P = 0.006; 19% higher on day 4, P = 0.001). In the
analysis of IV enoxaparin, obese individuals had higher
overall clearance (Cl) and Vd (p < 0.01); however, they had
a lower weight-based Cl and Vd. The authors concluded that
overall exposure is higher in obese patients when treated
with similar weight-based dosing regimens. However, an
analysis by Bazinet et al. which assessed the difference in PD
response to therapeutic dose enoxaparin between obese
(BMI ⩾ 30 kg/m2) and nonobese individuals was unable to

Hospital Pharmacy - December 2019

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