Abstract
Background
Venous thromboembolism (VTE) occurs in up to 900,000 people in the United States each year and there is more risk for those over 40 years old. 1 The incidence increases due to hospitalization, about 50% of VTE events occur because of a hospital admission. Patients in the hospital tend to have 1 or more risk factors for VTE. The American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients recommends unfractionated heparin and low molecular weight heparin are recommended for acutely and critically ill patients for pharmacological VTE prophylaxis. 2 Enoxaparin is a low molecular weight heparin. These guidelines also state that there is need for more research for the most appropriate dosing for patients that are overweight. 2 Obesity is another risk factor for VTE. There is a higher incidence of VTE rates in obese patients on the normal prophylactic enoxaparin dosing of 40 mg daily, as well as anti-Factor Xa levels that are not at the prophylactic level. 3
A literature review of optimal enoxaparin dosing strategies found that most studies evaluated anti-Factor Xa ranges to determine if the enoxaparin dose was appropriate, and a couple of the studies evaluated VTE outcomes. 3 The weight-based recommendations include enoxaparin 40 mg twice daily for patients with a BMI greater or equal to 40 kg/m2 and 60 mg twice daily for BMI greater or equal to 60 kg/m2. 3
In a retrospective cohort study, patients weighing more than 100 kg were evaluated for the occurrence for VTE after receiving enoxaparin 40 mg once daily to the high dose of twice daily. Patients that received the standard dose of enoxaparin 40 mg once daily had a VTE rate of 1.48% and those that receive the high dose of enoxaparin 40 mg twice daily had a VTE rate of .77% (P = .05). There was no increased risk of bleeding in the group that received the high dose enoxaparin. This study also mentioned that physicians had a low rate of adapting to this new dosing strategy. The main reasons stated physicians’ afraid of bleeding risks with higher doses or just not being aware of newer dosing recommendations. 4
Another study reviewed patients with a BMI greater than or equal to 30 kg/m2 and gave them a dose of 40 mg daily or 60 mg daily. More patients in the higher dose group had a normal anti-Xa level, which was classified as between .32 and .54 IU/mL. 31% of patients in the enoxaparin 40 mg daily group were in the normal range and 69% of patients receiving enoxaparin 60 mg daily were in normal range (P = .007). When looking at a subgroup of patients with a weight greater than 100 kg, there was a distinct difference found with fewer patients having an anti-Factor Xa level in the reference range (P = .009). 5
On March 6, 2020, two pharmacists presented at a system-wide Grand Rounds for a health-system in the Upper Midwest on enoxaparin dosing for patients with a BMI 40 kg/m2 or greater. Based on their research and other clinical dosing recommendations, these pharmacists recommended adjusted prophylactic VTE dosing of enoxaparin to 40 mg twice daily instead of once daily in patients with BMI 40 kg/m2 or greater. This study was conducted to determine if the education provided increased the number of obese patients receiving enoxaparin twice daily compared to once daily at a single center within the health-system.
Methods
This was a case-control study conducted at a single center hospital in the Upper Midwest. Data was extracted from electronic health records of acute care patients. The pharmacist-led presentation took place on March 6, 2020, with pharmacists, physicians, and other health care professionals in attendance. This informational presentation covered VTE epidemiology, risk factors, prevalence, mechanism in obesity and then into enoxaparin dosing strategies. The final recommendation was to use enoxaparin 40 mg twice daily in patients with a BMI of 40 kg/m2 or greater. The control group was defined as patients admitted March 5, 2018 to March 5, 2020 and the case group included admissions from March 7, 2020 to March 7, 2022. Two years prior to and following the presentation. This time frame was chosen for the case group to include the most amount of time up to data collection and the same was chosen for the control group. The study population inclusion criteria were patients 18 years and older, hospitalized with a need for VTE prophylaxis with enoxaparin, and having a BMI greater or equal to 40 kg/m2. Exclusion criteria included a COVID-19 diagnosis within 14 days prior or at the time of admission, as well as any bleeding events 3 months prior to or during admission. The bleeding events were determined by any ICD codes documented during hospitalization that had a correlation to bleeding. There was no maximum BMI cut off and the study was not limited to orders entered by physicians that attended the pharmacist-led education. The primary outcome was the number of patients with a BMI greater or equal to 40 kg/m2 who received enoxaparin 40 mg twice daily compared to those who received enoxaparin 40 mg once daily. Data was evaluated using binary logistic generalized linear models.
The BMI of patients were not extracted from the electronic health record. The patients’ weight (kg) was collected from the documented weight during the hospital admission. Not every patient has a height measured during hospital admission. Heights (m) were collected from the most recent height documented in the electronic health record. BMI was then calculated electronically as weight (kg)/height (m2).
Results
Characteristics and Outcomes of Patients.
aLOS: Length of Stay.
Number of Hospitalizations in Control Group and Case Group.
Number of Patients Who Received Enoxaparin 40 mg Once Daily Versus Twice Daily.
Discussion
The American Society of Hematology VTE prophylaxis guidelines do not include dosing recommendations for obese patients. Recent studies questioned if patients with elevated BMI should receive the same prophylactic enoxaparin dosing as patients without an elevated BMI. This study evaluates the implementation of enoxaparin 40 mg twice daily in patients with a BMI 40 mg/kg2 or greater after a pharmacist-led health system education on the efficacy and safety of this dosing regimen.
There was no difference in the number of patients that received enoxaparin 40 mg subcutaneously twice daily after the pharmacist-led education compared to before the education.
There are multiple limitations in this study. A single hospital site was evaluated; therefore, the results may not be as applicable to other sites. Part of the study period took place during the COVID-19 pandemic, this may have altered physician and pharmacist views about prophylactic enoxaparin dosing as many different dosing strategies were used throughout the pandemic. This occurred as it was discovered that COVID-19 positive patients had a higher risk of coagulopathy. These other dosing strategies were not evaluated because they were not the recommended dosing based on the pharmacist-led education. As a result of the COVID-19 pandemic there was a decrease in scheduled surgeries and a downtrend in admissions during the summer of 2020. People were also avoiding hospital settings during this time as well. The education took place days before the hospital had to shift practices due to the COVID-19 shutdown. The follow-up on this education was not prioritized as hospital workflows were changing rapidly.
It was not determined if patients were admitted for medical treatment or as a surgical patient. This may have impacted the prophylactic enoxaparin dosing chosen. The sample size is smaller in the control group compared to the case group. This may also be related to the lower census of the hospital before the beginning of the COVID-19 pandemic. As fewer COVID-19 patients are admitted over the course of the case group, the hospital census is still higher compared to the timeframe of the control group. This could also be due to an increase in population in the surrounding area. Throughout the 4-year timeframe of the study, few patients were a part of the study population. Having a BMI 40 kg/m2 or greater was the largest limiting factor as to why patients were not included in this study. The study does not evaluate possible recommendations made by pharmacists to physicians to increase the enoxaparin dosing and possible rejections to this recommendation by physician preference.
Conclusion
There was no difference in the number of patients receiving enoxaparin 40 mg twice daily following the pharmacist-led education about prophylactic enoxaparin dosing in obesity. To improve rates of high-dose enoxaparin in obese patients, health care facilities could implement pharmacist-to-dose weight-based policies. Another option would be creating weight-based order sets in the electronic health record. Continued education to pharmacists and physicians about the outcomes and safety data of increased prophylactic enoxaparin dosing in obese patients is needed due to unawareness about increased dosing requirements.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
