Semin Thromb Hemost 2016; 42(08): 846-856
DOI: 10.1055/s-0036-1593542
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Outpatient Treatment of Venous Thromboembolism: Operational Impact and the Role of Novel Anticoagulants

Benjamin White
1   Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts
,
Rachel Rosovsky
2   Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
,
Blair Alden Parry
1   Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts
,
Christopher Kabrhel
1   Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts
› Author Affiliations
Further Information

Publication History

Publication Date:
20 October 2016 (online)

Abstract

Pulmonary embolism (PE) and venous thromboembolism (VTE) are common diagnoses in the emergency department (ED), with significant potential morbidity and mortality. As a result, historically nearly all patients with PE have been admitted to the hospital for observation and treatment. In recent years, the ability to rapidly and accurately risk stratify patients with VTE according to their risk of short-term clinical deterioration has supported outpatient treatment, and non-vitamin K antagonist oral anticoagulants (NOACs) have further facilitated this approach. This review details the historical context and operational impact of managing VTE in the outpatient setting, describes a model for outpatient management of VTE, and suggests potential areas of further inquiry.

 
  • References

  • 1 Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis 2016; 41 (1) 3-14
  • 2 Chambers JG, Kabrhel C, Venkatesh AK, Schuur JD. Prevalence and patient predictors in outpatient treatment of venous thromboembolic disease. Ann Emerg Med 2013; 62 (4) S36
  • 3 Aujesky D, Perrier A, Roy P-M , et al. Validation of a clinical prognostic model to identify low-risk patients with pulmonary embolism. J Intern Med 2007; 261 (6) 597-604
  • 4 Aujesky D, Roy P-M, Le Manach CP , et al. Validation of a model to predict adverse outcomes in patients with pulmonary embolism. Eur Heart J 2006; 27 (4) 476-481
  • 5 Kabrhel C, Okechukwu I, Hariharan P , et al. Factors associated with clinical deterioration shortly after PE. Thorax 2014; 69 (9) 835-842
  • 6 Aujesky D, Roy P-M, 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 Wells PS, Büller HR. Outpatient treatment of patients with pulmonary embolism. Semin Vasc Med 2001; 1 (2) 229-234
  • 8 Wells PS. Outpatient treatment of patients with deep-vein thrombosis or pulmonary embolism. Curr Opin Pulm Med 2001; 7 (5) 360-364
  • 9 Penaloza A, Kline J, Verschuren F , et al. European and American suspected and confirmed pulmonary embolism populations: comparison and analysis. J Thromb Haemost 2012; 10 (3) 375-381
  • 10 Donzé J, Le Gal G, Fine MJ , et al. Prospective validation of the Pulmonary Embolism Severity Index. A clinical prognostic model for pulmonary embolism. Thromb Haemost 2008; 100 (5) 943-948
  • 11 Jiménez D, Aujesky D, Moores L , et al; RIETE Investigators. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med 2010; 170 (15) 1383-1389
  • 12 Kabrhel C, Sacco W, Liu S, Hariharan P. Outcomes considered most important by emergency physicians when determining disposition of patients with pulmonary embolism. Int J Emerg Med 2010; 3 (4) 239-264
  • 13 Hariharan P, Takayesu JK, Kabrhel C. Association between the Pulmonary Embolism Severity Index (PESI) and short-term clinical deterioration. Thromb Haemost 2011; 105 (4) 706-711
  • 14 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
  • 15 Wenzel RP, Edmond MB. The impact of hospital-acquired bloodstream infections. Emerg Infect Dis 2001; 7 (2) 174-177
  • 16 Yoo HH, Queluz TH, El Dib R. Outpatient versus inpatient treatment for acute pulmonary embolism. In: The Cochrane Collaboration, ed. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd; 2014. . Available at http://doi.wiley.com/10.1002/14651858.CD010019.pub2 . Accessed July 22, 2016
  • 17 Kahler ZP, Beam DM, Kline JA. Cost of treating venous thromboembolism with heparin and warfarin versus home treatment with rivaroxaban. Acad Emerg Med 2015; 22 (7) 796-802
  • 18 Beam DM, Kahler ZP, Kline JA. Immediate discharge and home treatment with rivaroxaban of low-risk venous thromboembolism diagnosed in two U.S. emergency departments: a one-year preplanned analysis. Acad Emerg Med 2015; 22 (7) 788-795
  • 19 Dexter L. The chair and venous thrombosis. Trans Am Clin Climatol Assoc 1973; 84: 1-15
  • 20 Galanaud J-P, Laroche J-P, Righini M. The history and historical treatments of deep vein thrombosis. J Thromb Haemost 2013; 11 (3) 402-411
  • 21 Anning ST. The historical aspects of venous thrombosis. Med Hist 1957; 1 (1) 28-37
  • 22 Mannucci PM. Venous thrombosis: the history of knowledge. Pathophysiol Haemost Thromb 2002; 32 (5–6) 209-212
  • 23 Parapia LA. History of bloodletting by phlebotomy. Br J Haematol 2008; 143 (4) 490-495
  • 24 Barral FG. Vena cava filters: why, when, what and how?. J Cardiovasc Surg (Torino) 2008; 49 (1) 35-49
  • 25 McLEAN J. The discovery of heparin. Circulation 1959; 19 (1) 75-78
  • 26 Charles AF, Scott DA. Studies on heparin: Observations on the chemistry of heparin. Biochem J 1936; 30 (10) 1927-1933
  • 27 Mueller RL, Scheidt S. History of drugs for thrombotic disease. Discovery, development, and directions for the future. Circulation 1994; 89 (1) 432-449
  • 28 Campbell HA, Link KP. Studies on the hemorrhagic sweet clover disease: IV. The isolation and crystallization of the hemorrhagic agent. J Biol Chem 1941; 138 (1) 21-33
  • 29 Link KP. The discovery of dicumarol and its sequels. Circulation 1959; 19 (1) 97-107
  • 30 Kearon C, Akl EA, Comerota AJ , et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2 Suppl): 419-494
  • 31 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
  • 32 Agnelli G, Buller HR, Cohen A , et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369 (9) 799-808
  • 33 Schulman S, Kearon C, Kakkar AK , et al; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361 (24) 2342-2352
  • 34 Büller HR, Décousus H, Grosso MA , et al; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013; 369 (15) 1406-1415
  • 35 Bauersachs R, Berkowitz SD, Brenner B , et al; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363 (26) 2499-2510
  • 36 Büller HR, Prins MH, Lensin AW , et al; EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366 (14) 1287-1297
  • 37 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
  • 38 Wells PS, Anderson DR, Rodger MA , et al. A randomized trial comparing 2 low-molecular-weight heparins for the outpatient treatment of deep vein thrombosis and pulmonary embolism. Arch Intern Med 2005; 165 (7) 733-738
  • 39 Piran S, Le Gal G, Wells PS , et al. Outpatient treatment of symptomatic pulmonary embolism: a systematic review and meta-analysis. Thromb Res 2013; 132 (5) 515-519
  • 40 Vinson DR, Zehtabchi S, Yealy DM. Can selected patients with newly diagnosed pulmonary embolism be safely treated without hospitalization? A systematic review. Ann Emerg Med 2012; 60 (5) 651-662.e4
  • 41 Institute of Medicine (US) Roundtable on Evidence-Based Medicine. The healthcare imperative: lowering costs and improving outcomes: workshop series summary. In: Yong PL, Saunders RS, Olsen L. eds. Washington, DC: National Academies Press; 2010
  • 42 Welch SJ, Stone-Griffith S, Asplin B, Davidson SJ, Augustine J, Schuur JD ; Second Performance Measures and Benchmarking Summit; Emergency Department Benchmarking Alliance. Emergency department operations dictionary: results of the second performance measures and benchmarking summit. Acad Emerg Med 2011; 18 (5) 539-544
  • 43 Jiménez D, Yusen RD, Otero R , et al. Prognostic models for selecting patients with acute pulmonary embolism for initial outpatient therapy. Chest 2007; 132 (1) 24-30
  • 44 Subramaniam RM, Mandrekar J, Blair D, Peller PJ, Karalus N. The Geneva prognostic score and mortality in patients diagnosed with pulmonary embolism by CT pulmonary angiogram. J Med Imaging Radiat Oncol 2009; 53 (4) 361-365
  • 45 Giannitsis E, Müller-Bardorff M, Kurowski V , et al. Independent prognostic value of cardiac troponin T in patients with confirmed pulmonary embolism. Circulation 2000; 102 (2) 211-217
  • 46 Pollack CV, Schreiber D, Goldhaber SZ , et al. Clinical characteristics, management, and outcomes of patients diagnosed with acute pulmonary embolism in the emergency department: initial report of EMPEROR (Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry). J Am Coll Cardiol 2011; 57 (6) 700-706
  • 47 Sánchez D, De Miguel J, Sam A , et al. The effects of cause of death classification on prognostic assessment of patients with pulmonary embolism. J Thromb Haemost 2011; 9 (11) 2201-2207
  • 48 Aujesky D, Obrosky DS, Stone RA , et al. A prediction rule to identify low-risk patients with pulmonary embolism. Arch Intern Med 2006; 166 (2) 169-175
  • 49 Janata K, Holzer M, Laggner AN, Müllner M. Cardiac troponin T in the severity assessment of patients with pulmonary embolism: cohort study. BMJ 2003; 326 (7384) 312-313
  • 50 Kucher N, Printzen G, Doernhoefer T, Windecker S, Meier B, Hess OM. Low pro-brain natriuretic peptide levels predict benign clinical outcome in acute pulmonary embolism. Circulation 2003; 107 (12) 1576-1578
  • 51 Kucher N, Printzen G, Goldhaber SZ. Prognostic role of brain natriuretic peptide in acute pulmonary embolism. Circulation 2003; 107 (20) 2545-2547
  • 52 La Vecchia L, Ottani F, Favero L , et al. Increased cardiac troponin I on admission predicts in-hospital mortality in acute pulmonary embolism. Heart 2004; 90 (6) 633-637
  • 53 ten Wolde M, Tulevski II, Mulder JWM , et al. Brain natriuretic peptide as a predictor of adverse outcome in patients with pulmonary embolism. Circulation 2003; 107 (16) 2082-2084
  • 54 Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 2011; 365 (21) 2002-2012
  • 55 Squizzato A, Galli M, Dentali F, Ageno W. Outpatient treatment and early discharge of symptomatic pulmonary embolism: a systematic review. Eur Respir J 2009; 33 (5) 1148-1155
  • 56 Beer JH, Burger M, Gretener S, Bernard-Bagattini S, Bounameaux H. Outpatient treatment of pulmonary embolism is feasible and safe in a substantial proportion of patients. J Thromb Haemost 2003; 1 (1) 186-187
  • 57 Büller HR, Davidson BL, Decousus H , et al; Matisse Investigators. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med 2003; 349 (18) 1695-1702
  • 58 Lim AYH, Parr DG, Stableforth DE, Fellows M, Fontaine R, Fegan CD. Early discharge and home supervision of patients with pulmonary embolism treated with low-molecular weight heparin. Eur J Intern Med 2003; 14 (2) 89-93
  • 59 Siragusa S, Arcara C, Malato A , et al. Home therapy for deep vein thrombosis and pulmonary embolism in cancer patients. Ann Oncol 2005; 16 (Suppl. 04) iv136-iv139
  • 60 Ong BS, Karr MA, Chan DKY, Frankel A, Shen Q. Management of pulmonary embolism in the home. Med J Aust 2005; 183 (5) 239-242
  • 61 Ageno W, Grimwood R, Limbiati S, Dentali F, Steidl L, Wells PS. Home-treatment of deep vein thrombosis in patients with cancer. Haematologica 2005; 90 (2) 220-224
  • 62 Olsson C-G, Bitzén U, Olsson B , et al. Outpatient tinzaparin therapy in pulmonary embolism quantified with ventilation/perfusion scintigraphy. Med Sci Monit 2006; 12 (2) PI9-PI13 (abstract)
  • 63 Davies CWH, Wimperis J, Green ES , et al. Early discharge of patients with pulmonary embolism: a two-phase observational study. Eur Respir J 2007; 30 (4) 708-714
  • 64 Lui B, Tran A, Montalto M. Treatment of patients with pulmonary embolism entirely in Hospital in the Home. Aust Fam Physician 2007; 36 (5) 381-384
  • 65 Agterof MJ, Schutgens REG, 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
  • 66 Otero R, Uresandi F, Jiménez D , et al. Home treatment in pulmonary embolism. Thromb Res 2010; 126 (1) e1-e5
  • 67 Rodríguez-Cerrillo M, Alvarez-Arcaya A, Fernández-Díaz E, Fernández-Cruz A. A prospective study of the management of non-massive pulmonary embolism in the home. Eur J Intern Med 2009; 20 (6) 598-600
  • 68 Zondag W, Mos ICM, Creemers-Schild D , et al; Hestia Study Investigators. Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study. J Thromb Haemost 2011; 9 (8) 1500-1507
  • 69 Kearon C, Ginsberg JS, Julian JA , et al; Fixed-Dose Heparin (FIDO) Investigators. Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA 2006; 296 (8) 935-942
  • 70 Hacobian M, Shetty R, Niles CM , et al. Once daily enoxaparin for outpatient treatment of acute venous thromboembolism: a case-control study. Clin Appl Thromb Hemost 2010; 16 (1) 21-25