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Low-RISK PE

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An evidence-based tool to guide the identification and outpatient treatment of patients with low-risk pulmonary embolism.

Section IconDiagnose Pulmonary Embolism
PE can be confirmed with one of the following:
Computed Tomographic Pulmonary Angiography (CTPA)
Ventilation-perfusion lung scan (V/Q)
PE may also be identified on pulmonary arteriography or pulmonary magnetic resonance arteriography (MRA).
A diagnosis of PE can also be made in patients with an identified deep venous thrombosis (DVT) and the presence of symptoms indicative of PE, but the absence of chest imaging precludes complete risk-stratification.
In addition to PE diagnostic testing, the following lab tests are required for risk stratification and medication selection:
Complete blood count, basic metabolic panel, troponin, and a pregnancy test (for women of childbearing age). Liver function and coagulation tests may also be helpful
References
  1. Barnes GD, Gafoor S, Wakefield T, Upchurch GR, Jr., Henke P, Froehlich JB. National trends in venous disease. J Vasc Surg. 2010;51(6):1467-1473.
  2. Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016;41(1):3-14.
  3. Smith SB, Geske JB, Kathuria P, et al. Analysis of National Trends in Admissions for Pulmonary Embolism. Chest. 2016;150(1):35-45.
  4. Jimenez S, Ruiz-Artacho P, Merlo M, et al. Risk profile, management, and outcomes of patients with venous thromboembolism attended in Spanish Emergency Departments: The ESPHERIA registry. Medicine (Baltimore). 2017;96(48):e8796.
  5. Kabrhel C, Rosovsky R, Channick R, et al. A Multidisciplinary Pulmonary Embolism Response Team: Initial 30-Month Experience With a Novel Approach to Delivery of Care to Patients With Submassive and Massive Pulmonary Embolism. Chest. 2016;150(2):384-393.
  6. Singer AJ, Thode HC, Jr., Peacock WFt. Admission rates for emergency department patients with venous thromboembolism and estimation of the proportion of low risk pulmonary embolism patients: a US perspective. Clin Exp Emerg Med. 2016;3(3):126-131.
  7. 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(6):597-604.
  8. Becattini C, Agnelli G. Risk stratification and management of acute pulmonary embolism. Hematology Am Soc Hematol Educ Program. 2016;2016(1):404-412.
  9. Kabrhel C, Okechukwu I, Hariharan P, et al. Factors associated with clinical deterioration shortly after PE. Thorax. 2014;69(9):835-842.
  10. Weeda ER, Kohn CG, Peacock WF, et al. External Validation of the Hestia Criteria for Identifying Acute Pulmonary Embolism Patients at Low Risk of Early Mortality. Clin Appl Thromb Hemost. 2017;23(7):769-774.
  11. Kovacs MJ, Anderson D, Morrow B, Gray L, Touchie D, Wells PS. Outpatient treatment of pulmonary embolism with dalteparin. Thromb Haemost. 2000;83(2):209-211.
  12. Wells PS. Outpatient treatment of patients with deep-vein thrombosis or pulmonary embolism. Curr Opin Pulm Med. 2001;7(5):360-364.
  13. Wells PS, Buller HR. Outpatient treatment of patients with pulmonary embolism. Semin Vasc Med. 2001;1(2):229-234.
  14. Aujesky D, Roy PM, Verschuren F, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet. 2011;378(9785):41-48.
  15. Singer AJ, Xiang J, Kabrhel C, et al. Multicenter Trial of Rivaroxaban for Early Discharge of Pulmonary Embolism From the Emergency Department (MERCURY PE): Rationale and Design. Acad Emerg Med. 2016;23(11):1280-1286.
  16. Barco S, Schmidtmann I, Ageno W, et al. Survival and quality of life after early discharge in low-risk pulmonary embolism. Eur Respir J. 2021;57(2).
  17. Bledsoe JR, Woller SC, Stevens SM, et al. Management of Low-Risk Pulmonary Embolism Patients Without Hospitalization: The Low-Risk Pulmonary Embolism Prospective Management Study. Chest. 2018;154(2):249-256.
  18. Kabrhel C, Rosovsky R, Baugh C, et al. Multicenter Implementation of a Novel Management Protocol Increases the Outpatient Treatment of Pulmonary Embolism and Deep Vein Thrombosis. Acad Emerg Med. 2019;26(6):657-669.
  19. Vinson DR, Ballard DW, Huang J, et al. Outpatient Management of Emergency Department Patients With Acute Pulmonary Embolism: Variation, Patient Characteristics, and Outcomes. Ann Emerg Med. 2018;72(1):62-72 e63.
  20. van der Wall SJ, Hendriks SV, Huisman MV, Klok FA. Home treatment of acute pulmonary embolism: state of the art in 2018. Curr Opin Pulm Med. 2018;24(5):425-431.
  21. Agterof MJ, Schutgens RE, Snijder RJ, et al. Out of hospital treatment of acute pulmonary embolism in patients with a low NT-proBNP level. J Thromb Haemost. 2010;8(6):1235-1241.
  22. Kline JA, Kahler ZP, Beam DM. Outpatient treatment of low-risk venous thromboembolism with monotherapy oral anticoagulation: patient quality of life outcomes and clinician acceptance. Patient Prefer Adherence. 2016;10:561-569.
  23. Malik AH, Aronow WS. Safety, efficacy, length of stay and patient satisfaction with outpatient management of low-risk pulmonary embolism patients - a meta-analysis. Arch Med Sci. 2021;17(1):245-251.
  24. Othieno R, Okpo E, Forster R. Home versus in-patient treatment for deep vein thrombosis. Cochrane Database Syst Rev. 2018;1:Cd003076.
  25. Simon LE, Iskin HR, Vemula R, et al. Emergency Department Patient Satisfaction with Treatment of Low-risk Pulmonary Embolism. West J Emerg Med. 2018;19(6):938-946.
  26. Ghazvinian R, Elf J, Lofvendahl S, Holst J, Gottsater A. Outpatient Treatment in Low-Risk Pulmonary Embolism Patients Receiving Direct Acting Oral Anticoagulants Is Associated With Cost Savings. Clin Appl Thromb Hemost. 2020;26:1076029620937352.
  27. Bledsoe JR, Woller SC, Stevens SM, et al. Cost-effectiveness of managing low-risk pulmonary embolism patients without hospitalization. The low-risk pulmonary embolism prospective management study. Am J Emerg Med. 2021;41:80-83.
  28. Shan J ID, Bath H, Johnson DJ, Julien D, Vinson DR. "Outpatient Management" of Pulmonary Embolism Defined in the Primary Literature: A Narrative Review. 2021;25(20):233.
  29. Westafer LM, Shieh MS, Pekow PS, Stefan MS, Lindenauer PK. Outpatient Management of Patients Following Diagnosis of Acute Pulmonary Embolism. Acad Emerg Med. 2021;28(3):336-345.
  30. Vinson DR, Mark DG, Ballard DW. Overcoming barriers to outpatient management of emergency department patients with acute pulmonary embolism. Acad Emerg Med. 2021;28(3):377-378.
  31. Crisp JG, Lovato LM, Jang TB. Compression ultrasonography of the lower extremity with portable vascular ultrasonography can accurately detect deep venous thrombosis in the emergency department. Ann Emerg Med. 2010;56(6):601-610.
  32. Pomero F, Dentali F, Borretta V, et al. Accuracy of emergency physician-performed ultrasonography in the diagnosis of deep-vein thrombosis: a systematic review and meta-analysis. Thromb Haemost. 2013;109(1):137-145.
  33. Karande GY, Hedgire SS, Sanchez Y, et al. Advanced imaging in acute and chronic deep vein thrombosis. Cardiovasc Diagn Ther. 2016;6(6):493-507.
Section IconRisk Stratify PE and Identify Patients Safe for Outpatient Management
Psychosocial criteria for home discharge
Issues that may limit compliance:
  • Homelessness
  • Untreated substance use disorder
  • Dysregulated psychiatric disease
  • Lack of ability to follow up (e.g. transportation)
  • Lack of ability to obtain medications (e.g. no insurance)
  • Any other condition that the physician deems as high risk for noncompliance
Clinical criteria for home discharge
No evidence of hemodynamic instability (including syncope) pre-hospital or during ED course
Negative Hestia Criteria Learn More
No high-risk features on CTPA
  • RV:LV ratio >1
  • Main pulmonary artery PE or saddle PE
  • Clot visualized in the heart
No high-risk features on echocardiogram (bedside or formal), if performed
  • Echocardiogram should be considered if CTPA shows evidence of right ventricular strain (e.g. RV:LV ratio >1)
  • Right ventricular hypokinesis
  • Bowing of the intraventricular septum (i.e. D-sign)
  • Clot visualized in the heart
No high-risk features on laboratory testing
  • Troponin elevated
No high-risk features on lower extremity venous ultrasound (bedside or formal) or venograpy, if performed
  • Lower extremity venous imaging should be considered when a patient has leg pain, swelling, redness, or evidence of venous distension
  • DVT in iliofemoral vein
  • Evidence of phlegmasia cerulea or alba dolens
No high-risk features on ECG.
  • New right heart strain pattern, including;
    • Right bundle branch block
    • Deep T wave inversions in anterior precordial leads
    • S1Q3T3 pattern
    • New onset atrial fibrillation
If high-risk features on ECG, evaluate for right heart strain with echocardiogram
References
  1. Elias A, Mallett S, Daoud-Elias M, Poggi JN, Clarke M. Prognostic models in acute pulmonary embolism: a systematic review and meta-analysis. BMJ Open. 2016;6(4):e010324.
  2. Zondag W, Mos IC, Creemers-Schild D, et al. Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study. J Thromb Haemost. 2011;9(8):1500-1507.
  3. Peacock FW, Coleman CI, Diercks DB, et al. Emergency Department Discharge of Pulmonary Embolus Patients. Acad Emerg Med. 2018;25(9):995-1003.
  4. Barco S, Schmidtmann I, Ageno W, et al. Survival and quality of life after early discharge in low-risk pulmonary embolism. Eur Respir J. 2021;57(2).
  5. Aujesky D, Obrosky DS, Stone RA, et al. Derivation and validation of a prognostic model for pulmonary embolism. American journal of respiratory and critical care medicine. 2005;172(8):1041-1046.
  6. Aujesky D, Roy PM, Verschuren F, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet. 2011;378(9785):41-48.
  7. Bledsoe JR, Woller SC, Stevens SM, et al. Management of Low-Risk Pulmonary Embolism Patients Without Hospitalization: The Low-Risk Pulmonary Embolism Prospective Management Study. Chest. 2018;154(2):249-256.
  8. Vinson DR, Mark DG, Chettipally UK, et al. Increasing Safe Outpatient Management of Emergency Department Patients With Pulmonary Embolism: A Controlled Pragmatic Trial. Ann Intern Med. 2018;169(12):855-865.
  9. Jimenez D, Aujesky D, Moores L, et al. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med. 2010;170(15):1383-1389.
  10. Roy PM. Hestia rule versus simplified PESI for home treatment of patients with acute pulmonary embolism: A multinational randomised clinical trial (HOME-PE). Eur Heart J 2021 (in press).
  11. Konstantinides SV. Home treatment of pulmonary embolism: are all the questions answered now after the HOME-PE trial? Cardiovasc Res. 2020;116(13):e179-e181.
  12. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-352.
  13. Vinson DR, Engelhart DC, Bahl D, et al. Presyncope Is Associated with Intensive Care Unit Admission in Emergency Department Patients with Acute Pulmonary Embolism. West J Emerg Med. 2020;21(3):703-713.
  14. Digby GC, Kukla P, Zhan ZQ, et al. The value of electrocardiographic abnormalities in the prognosis of pulmonary embolism: a consensus paper. Ann Noninvasive Electrocardiol. 2015;20(3):207-223.
  15. El-Menyar A, Sathian B, Al-Thani H. Elevated serum cardiac troponin and mortality in acute pulmonary embolism: Systematic review and meta-analysis. Respir Med. 2019;157:26-35.
  16. Becattini C, Maraziti G, Vinson DR, et al. Right ventricle assessment in patients with pulmonary embolism at low risk for death based on clinical models: an individual patient data meta-analysis. Eur Heart J. 2021.
  17. Lankeit M, Friesen D, Aschoff J, et al. Highly sensitive troponin T assay in normotensive patients with acute pulmonary embolism. Eur Heart J. 2010;31(15):1836-1844.
  18. den Exter PL, Zondag W, Klok FA, et al. Efficacy and Safety of Outpatient Treatment Based on the Hestia Clinical Decision Rule with or without N-Terminal Pro-Brain Natriuretic Peptide Testing in Patients with Acute Pulmonary Embolism. A Randomized Clinical Trial. American journal of respiratory and critical care medicine. 2016;194(8):998-1006.
  19. Klok FA, Mos IC, Huisman MV. Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism: a systematic review and meta-analysis. American journal of respiratory and critical care medicine. 2008;178(4):425-430.
  20. Becattini C, Agnelli G, Vedovati MC, et al. Multidetector computed tomography for acute pulmonary embolism: diagnosis and risk stratification in a single test. Eur Heart J. 2011;32(13):1657-1663.
  21. Meinel FG, Nance JW, Jr., Schoepf UJ, et al. Predictive Value of Computed Tomography in Acute Pulmonary Embolism: Systematic Review and Meta-analysis. Am J Med. 2015;128(7):747-759.e742.
  22. Hariharan P, Dudzinski DM, Rosovsky R, et al. Relation Among Clot Burden, Right-Sided Heart Strain, and Adverse Events After Acute Pulmonary Embolism. Am J Cardiol. 2016;118(10):1568-1573.
  23. Gouin B, Blondon M, Jimenez D, et al. Clinical Prognosis of Nonmassive Central and Noncentral Pulmonary Embolism: A Registry-Based Cohort Study. Chest. 2017;151(4):829-837.
  24. Méan M, Tritschler T, Limacher A, et al. Association between computed tomography obstruction index and mortality in elderly patients with acute pulmonary embolism: A prospective validation study. PLoS One. 2017;12(6):e0179224.
  25. Pruszczyk P, Goliszek S, Lichodziejewska B, et al. Prognostic value of echocardiography in normotensive patients with acute pulmonary embolism. JACC Cardiovasc Imaging. 2014;7(6):553-560.
  26. Cho JH, Kutti Sridharan G, Kim SH, et al. Right ventricular dysfunction as an echocardiographic prognostic factor in hemodynamically stable patients with acute pulmonary embolism: a meta-analysis. BMC Cardiovasc Disord. 2014;14:64.
  27. Dudzinski DM, Hariharan P, Parry BA, Chang Y, Kabrhel C. Assessment of Right Ventricular Strain by Computed Tomography Versus Echocardiography in Acute Pulmonary Embolism. Acad Emerg Med. 2017;24(3):337-343.
  28. Trujillo-Santos J, den Exter PL, Gomez V, et al. Computed tomography-assessed right ventricular dysfunction and risk stratification of patients with acute non-massive pulmonary embolism: systematic review and meta-analysis. J Thromb Haemost. 2013;11(10):1823-1832.
  29. Garvey S, Dudzinski DM, Giordano N, Torrey J, Zheng H, Kabrhel C. Pulmonary embolism with clot in transit: An analysis of risk factors and outcomes. Thromb Res. 2020;187:139-147.
  30. Barrios D, Rosa-Salazar V, Jiménez D, et al. Right heart thrombi in pulmonary embolism. Eur Respir J. 2016;48(5):1377-1385.
  31. Barrios D, Rosa-Salazar V, Morillo R, et al. Prognostic Significance of Right Heart Thrombi in Patients With Acute Symptomatic Pulmonary Embolism: Systematic Review and Meta-analysis. Chest. 2017;151(2):409-416.
  32. Koć M, Kostrubiec M, Elikowski W, et al. Outcome of patients with right heart thrombi: the Right Heart Thrombi European Registry. Eur Respir J. 2016;47(3):869-875.
  33. Jimenez D, Aujesky D, Diaz G, et al. Prognostic significance of deep vein thrombosis in patients presenting with acute symptomatic pulmonary embolism. American journal of respiratory and critical care medicine. 2010;181(9):983-991.
  34. Kabrhel C, Okechukwu I, Hariharan P, et al. Factors associated with clinical deterioration shortly after PE. Thorax. 2014;69(9):835-842.
  35. Ortel TL, Neumann I, Ageno W, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv. 2020;4(19):4693-4738.
Section IconRisk Stratify for Bleeding on Anticoagulation
Patients at high-risk of anticoagulant-related bleeding should be admitted
Examples of high bleeding risk:
  • Active bleeding
  • Previous clinically significant bleeding including: Bleeding in a critical area or organ (e.g. intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, pericardial, intramuscular with compartment syndrome, hemoptysis, airway bleeding), or other bleeding requiring intervention.
  • Recent major surgery
  • Recent major trauma (including closed head injury without bleeding)
  • Recent stroke
  • Malignancy in a critical site (e.g. intracranial, spinal, ocular, oropharyngeal, retroperitoneal)
  • Thrombocytopenia (platelet count <75,000)
  • Cirrhosis or severe alcohol use disorder
  • High risk of falling
  • Use of medications that interact with anticoagulants or significantly increase risk of bleeding
Bleeding risk scores
Bleeding risk scores (e.g. VTE-BLEED, HAS-BLED, HEMORR2HAGES) may also be helpful in gauging long-term risk of anticoagulation related bleeding.
Section IconSelect and Start an Anticoagulant
Anticoagulants
DOACs are preferred for most patients
DOACs that do not require initial parenteral anticoagulant
Apixaban (Eliquis): 10 mg twice daily for 7 days followed by 5 mg twice daily
Rivaroxaban (Xarelto): 15 mg twice daily for 21 days followed by 20 mg daily; must be taken with food
DOACs that do require initial parenteral anticoagulant
Dabigatran (Pradaxa): 150 mg twice daily AFTER parenteral agent for 5-10 days; cannot be crushed
Edoxaban (Savaysa): 60 mg daily AFTER parenteral agent for 5-10 days
LMWH or fondaparinux must be given for the first 5 days
  • LMWH: enoxaparin sodium (Lovenox), 1 mg/kg SC twice daily or dalteparin sodium (fragmin), 200 IU/kg SC daily
  • Fondaparinux: 5 mg (body weight <50 kg), 7.5 mg (50 to 100 kg), or 10 mg (>100 kg) SC once daily
LMWH/Warfarin may be used when a DOAC is contraindicated or otherwise inappropriate
LMWH: dalteparin sodium (fragmin), 200 IU/kg SC daily or enoxaparin sodium (Lovenox), 1 mg/kg SC twice daily
Warfarin: 5 mg daily po, beginning after the first dose of LMWH/fondaparinux
Contraindications to DOACs
Antiphospholipid syndrome
Severe renal impairment (creatinine clearance <30 mL/min)
Certain cancers (e.g. GI, GU, brain or brain mets)
Liver impairment
Obesity (>120 kg or BMI >40)
Malabsorption such as gastric bypass
Pregnancy
Contraindications to LMWH
Severe renal impairment (creatinine clearance <30 mL/min)
Bacterial endocarditis
Body weight <50 kg
Contraindications to warfarin therapy
Pregnancy
History of warfarin-induced skin necrosis
Concurrent medications that interact with warfarin (e.g. antifungals, antibiotics, CYP2C9, 1A2, or 3A4 inhibitors/inducers)
References
  1. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). European Respiratory Journal. 2019;54(3):1901647.
  2. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-352.
  3. Agnelli G, Buller HR, Cohen A, et al. Oral Apixaban for the Treatment of Acute Venous Thromboembolism. New England Journal of Medicine. 2013;369(9):799-808.
  4. Oral Rivaroxaban for Symptomatic Venous Thromboembolism. New England Journal of Medicine. 2010;363(26):2499-2510.
  5. Raskob GE, van Es N, Verhamme P, et al. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med. 2018;378(7):615-624.
  6. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism. New England Journal of Medicine. 2009;361(24):2342-2352.
  7. Edoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism. New England Journal of Medicine. 2013;369(15):1406-1415.
  8. Raskob GE, van Es N, Verhamme P, et al. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. New England Journal of Medicine. 2017;378(7):615-624.
  9. Young AM, Marshall A, Thirlwall J, et al. Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D). J Clin Oncol. 2018;36(20):2017-2023.
  10. McBane RD, 2nd, Wysokinski WE, Le-Rademacher JG, et al. Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial. J Thromb Haemost. 2020;18(2):411-421.
  11. Agnelli G, Becattini C, Meyer G, et al. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. New England Journal of Medicine. 2020;382(17):1599-1607.
  12. Bates SM, Rajasekhar A, Middeldorp S, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood Advances. 2018;2(22):3317-3359.
Section IconFollow-up and Patient Education
Discharge Planning
Assure that the patient has a good home support system
Assure that the patient does not have a history of non-adherence to treatment
Giving the first dose of anticoagulant in the ED is recommended
Assure that patient has medication in-hand or can fill prescription upon discharge
Involving Case Management can be helpful with insurance, medication, and appointment barriers
Observation stays can provide time to address insurance, medication, and appointment barriers
Assure that the patient has timely clinic follow up. If needed, consider observation admission or hospitalization so that follow-up can be arranged
Obtain baseline CBC, platelets, creatinine, pregnancy test, PT/INR
General Medication Instructions
Educate patient to inform their healthcare team (e.g. PCP, pharmacist) that they are taking an anticoagulant.
Inform patients that their clinician may want them to stop taking the anticoagulant before having surgery, dental work or other procedures.
Inform women to contact the anticoagulant clinic or their PCP immediately if they become or are planning to become pregnant.
Inform women that they can take LMWH/warfarin while breastfeeding, but not DOACs.
Educate patients on methods to reduce the risk of bleeding (e.g. use soft toothbrush, shave with electric razor, use appropriate safety equipment, avoid ASA and NSAIDs, and avoid contact sports or activities with risk of falling or injury)
DOAC Specific Medication Instructions
Assure that the patient has timely clinic follow up (e.g. 7-10 days, or before dose change). If needed, consider observation admission or hospitalization so that follow-up can be arranged.
Educate patient that dose changes are required for apixaban (day 7) and rivaroxaban (day 21)
Educate patient that rivaroxaban should be taken with food
Educate patient that dabigatran and edoxaban need 5-10d LMWH lead-in before starting DOAC (see LMWH info below)
Educate patient about what to do if they miss a dose or take an extra dose.
If taking medication twice a day and >6 hours until next scheduled dose, take a dose ASAP. If <6 hours until next dose, skip the missed dose and take the next scheduled dose.
If taking medication once a day and you miss one of the doses, take it asap if >12 hours until the next scheduled dose. If <12 hours until next dose, skip the missed dose and take the next scheduled dose.
If patient takes a double dose, skip next scheduled dose and take the following dose the next day as scheduled.
LMWH + Warfarin Specific Medication Instructions
Assure that the patient has timely follow up for INR check (e.g. in 2-3 days). If needed, consider observation admission or hospitalization so that follow-up can be arranged.
Make sure patient has follow-up with clinician within 3-5 days
Prescribe enough LMWH to reach follow up and to ensure a minimum of 5 days overlap with warfarin
Typical starting warfarin dose is 5 mg daily, beginning after the first dose of LMWH
Warfarin should be taken the same time each day, preferably in the evening
Review the patient's medications for potential drug-drug interactions and discuss drug-food interactions (e.g., food rich in Vit K)
Educate patient on LWMH self-administration and assure proper technique
LMWH kits with instructions, record of daily injections, sterile alcohol swabs and sharps collector, may be helpful
Educate patient about what to do if they miss a dose or take an extra dose.
If patient misses a dose, skip it and wait until the next schedule dose. Don’t take a double dose to make up for missed dose.
If patient misses two or more days in a row, contact the anticoagulant clinic or your clinician. The dose may need to be changed.
If patient takes a higher dose than prescribed, contact the anticoagulant clinic or your clinician.
Return Precautions
Call PCP immediately for signs of minor bleeding (e.g. heavy menstrual periods, bleeding from your nose, gums, urine, or from a cut)
Return to the ER for any signs of major bleeding or worsening PE or DVT (e.g. CP, SOB, fast heartbeat, sweating, lightheadedness, fainting, vomiting blood or coughing up dark brown mucus, bleeding from your rectum, sudden severe back pain, severe nose bleeds which doesn’t stop quickly despite pressure (within 10 min), any other visible bleeding that will not stop, severe fall or injury to the head, severe or usual headache with symptoms like slurred speech, arm weakness, or facial drooping).
Return to the ER for any head injury or other significant trauma
Return to the ER if unable to obtain anticoagulant through PCP or anticoagulant clinic
Keys to successful outpatient management
A good home support system
No history of non-adherence to treatment
Ability to fill prescriptions (e.g. financial, transportation)
Insurance coverage may need to be confirmed by case management
Ability to follow-up in the clinic
References
  1. Kline JA, Kahler ZP, Beam DM. Outpatient treatment of low-risk venous thromboembolism with monotherapy oral anticoagulation: patient quality of life outcomes and clinician acceptance. Patient Prefer Adherence. 2016;10:561-569.
  2. Kabrhel C, Rosovsky R, Baugh C, et al. Multicenter Implementation of a Novel Management Protocol Increases the Outpatient Treatment of Pulmonary Embolism and Deep Vein Thrombosis. Acad Emerg Med. 2019;26(6):657-669.
  3. Kabrhel C, Rosovsky R, Baugh C, et al. The creation and implementation of an outpatient pulmonary embolism treatment protocol. Hosp Pract (1995). 2017;45(3):123-129.
  4. Simon LE, Iskin HR, Vemula R, et al. Emergency Department Patient Satisfaction with Treatment of Low-risk Pulmonary Embolism. West J Emerg Med. 2018;19(6):938-946.
  5. Peacock WF, Singer AJ. Reducing the hospital burden associated with the treatment of pulmonary embolism. J Thromb Haemost. 2019;17(5):720-736.
  6. Vinson DR, Ballard DW, Huang J, et al. Timing of discharge follow-up for acute pulmonary embolism: retrospective cohort study. West J Emerg Med. 2015;16(1):55-61.
  7. Condliffe R. Pathways for outpatient management of venous thromboembolism in a UK centre. Thrombosis journal. 2016;14:47.
Section IconPearls and Pitfalls
Systematic, inter-departmental protocols that support outpatient treatment may lead to sustained success
Reliable access to anticoagulant medications is essential for outpatient treatment of low-risk PE
Case Management and Pharmacy Resources may improve access to anticoagulant medications:
  • A "Med to Bed" or similar programs whereby patients are discharged with their medications in-hand
  • The patient's pharmacy may be able to confirm that the anticoagulant is covered by their insurance, without the need for a prior authorization
  • A "starter pack" of a DOAC can assist patients in successfully transitioning their dose at week 1 or 3
Drug manufacturers may offer low-cost, short-term access to medications through their websites for eligible patients
Consider an observation stay for the first dose of anticoagulant and to provide access to case management and pharmacy resources
Follow-up must be arranged prior to discharge
Closed loop communication with the follow-up clinician is recommended
For patients without a PCP, an alternative system that facilitates reliable follow up is essential
Patients with borderline creatinine clearance, advanced age, or other comorbid conditions should be considered for early follow up
For patients with uncontrolled hypertension, use caution when considering outpatient anticoagulant therapy
References
  1. Hayes BD, Zaharna L, Winters ME, Feemster AA, Browne BJ, Hirshon JM. To-Go medications for decreasing ED return visits. Am J Emerg Med. 2012;30(9):2011-2014.
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Acknowledgments

Developed by the ACEP Expert Panel on Low-Risk Pulmonary Embolism
and Low-Risk Deep Vein Thrombosis
Reviewed by the ACEP Clinical Resource Review Committee

CONTRIBUTORS
Christopher Kabrhel MD, MPH, FACEP, FAAEM (chair) Anna Marie Chang, MD Jackeline Hernandez-Nino, MD Alice M. Mitchell, MD, FACEP Rachel Rosovsky, MD, MPH David R. Vinson, MD, FACEP Stephen J. Wolf, MD, FACEP

 

ACEP Staff
Jerry Anderson Riane V. Gay, MPA, CAE Liz Muth

 

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