So, you diligently use PERC and Well’s and d-dimer and they were all positive on your patient who presented with chest pain and dyspnea. You obtained a pulmonary CT angiogram and found a pulmonary embolism. Easy admission, right? Well not so fast. Your patient may be a candidate for outpatient treatment. Who is truly safe to go home?
Venous thromboembolism is a major public health concern in the United States with estimates that 1-2 per 1000 individuals may be affected each year (300-600,000 individuals per year).  An analysis of healthcare claims from 1998-2004 estimated that the total annual healthcare cost for primary diagnosis of VTE is about $10,000 (DVT) to $16,000 (PE).  This conservatively equates to total annual costs of $3 billion to $10 billion attributable to VTE in the US. This care has likely only gotten more expensive in the past 10 years. A more recent study using data from 2011 determined the average US admission for PE was 5.1 days and cost $37,000. The averaged DVT admission was 4.7 days costing $30,000 (totaling > $10 billion annually in US) for 2011. 
Studies indicate outpatient treatment is safe and feasible for select groups of patients diagnosed with pulmonary embolism. Canadian studies in the early 2000s demonstrated that nearly 50 percent of patients could be treated as outpatients with acute pulmonary embolism. This strategy had not been widely accepted outside of Canada but is now being considered and adopted elsewhere. Estimates are as high as 45-50% of patients that are traditionally admitted for pulmonary embolism treatment may be treated as outpatient. [4,5] A review by Kohn et al of clinical prediction rules classified 22-45% of patients as low risk for mortality in theses study populations.  So conservatively 20-50% of patients may be safely managed as outpatients.
ACCP (American College of Chest Physicians) 2016 guidelines recommends outpatient treatment for low risk patients with an adequate social situation (well-maintained living conditions, strong support group, access to phone, patient feels well enough to go, and ability to quickly be re-hospitalized) and follow-up available. This was given a grade 2B recommendation (weak recommendation based on moderate quality evidence). 
ACEP (American College Emergency Physicians) has given this a Class III recommendation as of 2018, “Selected patients with acute PE who are at low risk for adverse outcomes as determined by PESI, simplified PESI (sPESI), or the Hestia criteria may be safely discharged from the ED on anticoagulation, with close outpatient follow-up.” They cite the following as potential benefits of implementing this treatment strategy: 
- Reduced inpatient treatment-related complications (i.e., hospital-acquired infections)
- Reduced cost compared with inpatient patient care
- Reduced hospital inpatient crowding
- Reduced time associated with treatment follow-up
- Better use of health care resources
- Improved patient satisfaction as a result of more efficient patient care and the ability to be treated at home
PESI (Pulmonary Embolism Severity Index) is a prediction rule used to risk stratify patients diagnosed with pulmonary embolism. It was originally used to estimate 30-day mortality in patients with acute pulmonary embolism using 11 variables. [9,10] Patients in Class I or II are considered low risk for mortality and may be a candidate for outpatient treatment of pulmonary embolism. This tool is advantageous as it can also help to identify patients at high risk for mortality that may need consideration for ICU admission or further work-up with 2D-Echocardiogram, cardiac biomarkers such as troponin or BNP (brain natriuretic peptide) to identify right heart strain and ultimately possible TPA (tissue plasminogen activator) administration.
- Age (1 point per year)
- Male (10 points)
- History of cancer (30 points)
- History of heart failure (10 points)
- History of chronic lung disease (10 points)
- Heart rate >109 (20 points)
- Systolic blood pressure < 100 (30 points)
- Respiratory rate > 29 (20 points)
- Temperature < 36 C (20 points)
- Altered mental status (60 points)
- Oxygen < 90% (20 points)
|PESI score||Class||Risk 30-day mortality|
The Simplified PESI (Pulmonary Embolism Severity Index) tool is one of the easiest and most validated for the emergency clinicians to use for risk stratification to identify those of low risk who may fit criteria for outpatient treatment. The simplified PESI relies on 6 easily identifiable factors to identify low risk patients for mortality from their PE. [11,12]
- Age < 81
- No history of cancer
- No history of COPD
- Heart rate < 110
- Systolic BP > 99
- Oxygen saturation > 89%
If the patient has a score of zero on the simplified PESI (i.e. none of the 6 factors are present), the patient is considered low risk. The overall 30-day mortality risk if the score is zero is 1%. The overall 30-day mortality for any score > 0 is 8.9% with severe morbidity of 2.7%. The score in simplified PESI is not additive, so once you have any positive criteria, the overall mortality is 8.9%. But at this point, you should be admitting your patient and considering further critical treatments. If you have a score of 1 or greater, you can use the original PESI to further risk stratify your patient.
There are several other clinical prediction rules and risk-stratification schemes that have been studied with varying degrees of performance – ESC, GRACE, Geneva, Aujesky, and others.  Kohn, et all reviewed 11 clinical prediction models/risk stratification methods for acute pulmonary embolism to determine accuracy for identifying patients with acute pulmonary embolism at low risk for mortality.  The specificity was less than 48% for the top 5 most sensitive models (with regards to sensitivity). Several models were based on data from studies with lower levels of evidence.
|Clinical Prediction Rule||Sensitivity||Specificity||Low risk %||Level of Evidence|
|PESI||0.89 (0.87-0.90)||0.49 (0.44-0.53)||45%||High|
|sPESI||0.92 (0.89-0.94)||0.38 (0.32-0.44)||35%||High|
|Geneva||0.41 (0.29-0.55)||0.85 (0.81-0.88)||82%||High|
|ESC||0.88 (0.77-0.94)||0.38 (0.28-0.49)||36%||High|
|Hestia||0.82 (0.52-0.95)||0.56 (0.52-0.61)||55%||Low|
|GRACE||0.99 (0.89-1.00)||0.27 0.21-0.34)||22%||Low|
|Aujesky||0.97 (0.95-0.99)||0.24 (0.19-0.31)||22%||Low|
It is important to recognize performance: limitations, sensitivity/specificity, and validation of each of these rules before putting them into practice. Perhaps the simplest to use in the emergency setting is sPESI. Other clinicians have advocated adding surrogate markers of RV strain (cardiac biomarkers such as troponin I and BNP) or direct measurement of RV size (looking for dilatation) on limited cardiac ultrasound in combination with sPESI or other clinical prediction models. [14-16] Jimenez et al reviewed the use of sPESI and BNP and found a negative predictive value of 99% for 30-day outcome of complicated course from PE (death, recurrent PE or hemodynamic collapse).  Others have refuted this and found that adding RV strain markers (troponin) or US provided no performance benefit to the PESI and HESTIA predictive models. [17-18] More research is likely needed in this area to determine which biomarker or US may or may not provide additional prognostic information to individual predictive models.
Long, et al have proposed the following algorithm as an approach to determining if your acute pulmonary embolism patient may be safely discharged. This algorithm has not been validated, but it incorporates the clinical prediction models that are already discussed. 
You ultimately determine your patient is a good fit for going home. What will you send them on? What else do you need to consider? Can they afford it?
The American College of Chest Physicians published updated guidelines on the management of venous thromboembolism in 2016. Included in this guideline were updated recommendations regarding pharmaceutical therapy. “For VTE without an associated cancer diagnosis, all direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, or edoxaban) are recommended over vitamin K antagonist (VKA) therapy (all Grade 2B) and VKA therapy is recommended over low molecular weight heparin (LMWH; Grade 2C).” 
If your patient does not have an associated cancer diagnosis, has normal renal function and good follow-up, you can consider sending them home on a direct oral anticoagulant. This should involve shared decision-making with the patient as this is still a novel management in the US. It should be noted from the table below that dabigatran and edoxaban still require bridging with low-molecular weight heparin. Rivaroxaban and apixaban do not require this bridging. It is also important to consider whether or not your patient will be able to afford the medication as it can be costly. For example, current published prices for apixaban range from $420-$461 at US pharmacies. However, there is a manufacturer coupon available for apixaban that allows the patient to get a 30-day free trial as well as a manufacturer coupon available for $10 per month with commercial insurance. (www.eliquis.bmscustomerconnect.com) However, these costs and coupons may change, so it’s always a good idea to check at the time of discharge that the patient will be able to secure their prescriptions.
We use a reference table created by our emergency pharmacists for prescribing oral anticoagulation. It’s also notable that the dosing and need for bridging is not the same when prescribing the same drug for atrial fibrillation versus venous thromboembolism treatment. Therefore, it’s wise to review a reference before prescribing these newer agents.
The landscape of venous thromboembolism treatment has changed drastically over the past ten years. First, we began treating DVT as an outpatient. Now we are beginning to do the same for a subset of patients with pulmonary embolism. It’s important to consider this on a case by case basis because pulmonary embolism is associated with a high mortality, but this is certainly an option in a subset of patients who are at low risk for complication from their acute pulmonary embolism.
Sydney Leach, MD & Jessica Nesheim, PharmD
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- LaMori JC, Shoheiber O, Mody SH, Bookhart BK. Inpatient resource use and cost burden of deep vein thrombosis and pulmonary embolism in the United States. Clin 2015 Jan 1;37(1):62-70
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- Baglin T. Fifty per cent of patients with pulmonary embolism can be treated as outpatients. J Thromb Haemost 2010; 8: 2404–5.
- Kohn CG, Mearns ES, Parker MW, et al. Prognostic Accuracy of Clinical Prediction Rules for Early Post-Pulmonary Embolism All-Cause Mortality: A Bivariate Meta-analysis. Chest 2015 Apr 1;147(4):1043-62.
- Kearon, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016;149:315-352
- ACEP Clinical Policies Subcommittee. Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department with Suspected Acute Venous Thromboembolic Disease. Ann Emerg Med 2018; 71(5): e59-109
- Aujesky D., Roy R M., Le Manach C.P., et al: Validation of a model to predict adverse outcomes in patients with pulmonary embolism. Eur Heart J 2006; 27; 261:476-81
- Aujesky D., Perrier A., Roy PM, et al: Validation of a clinical prognostic model to identify low-risk patients with pulmonary embolism. J Intern Med 2007; 261:597-604
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- Righini M., Roy P.M., Meyer G., Verschuren F., Aujesky D., and Le Gal G.: The Simplified Pulmonary Embolism Severity Index (SPESI): validation of a clinical prognostic model for pulmonary embolism. J Thromb Haemost 2011; 9 (10): 2115-7
- Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie N, Pruszczyk P, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008;29(18):2276–31.
- Jimenez D., Kopecna D., Tapson V., et al: Derivation and validation of multimarker prognostication for normotensive patients with acute symptomatic pulmonary embolism. Am J Respir Crit Care Med 2014; 189: pp. 718-726
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- Singanayagam A., Scally C., Al-Khairalla M.Z., et al: Are biomarkers additive to pulmonary embolism severity index for severity assessment in normotensive patients with acute pulmonary embolism? QJM 2011; 104: pp. 125-131
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- Zondag W., Vingerhoets L.M., Durian M.F., et al: Hestia criteria can safely select patients with pulmonary embolism for outpatient treatment irrespective of right ventricular function. J Thromb Haemost 2013; 11: pp. 686-692
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