Int J Angiol 2022; 31(03): 155-161
DOI: 10.1055/s-0042-1750329
Invited Article

Contemporary Treatment of Pulmonary Embolism: Medical Treatment and Management

1   Division of Cardiovascular Medicine, Texas Tech University Health Sciences Center, El Paso, Texas
,
1   Division of Cardiovascular Medicine, Texas Tech University Health Sciences Center, El Paso, Texas
,
1   Division of Cardiovascular Medicine, Texas Tech University Health Sciences Center, El Paso, Texas
› Author Affiliations

Abstract

Pulmonary embolus (PE) is defined as obstruction of the pulmonary artery or one of its branches by material (e.g., thrombus, tumor, air, or fat) but most commonly due to thrombus originating from the lower extremity deep veins.

We reviewed the current literature describing the optimal medical treatment and management of PE.

Databases (PubMed, the Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL) were searched for relevant studies and guidelines for management of patients with PE.

The initial approach to patients with suspected PE should focus upon stabilizing the patient while further workup for risk stratification is in progress. In most cases, anticoagulation should ideally be started even prior to confirming PE, if risk–benefit regarding suspicion of PE and bleeding risk is favorable.

Once the diagnosis is confirmed, risk stratification will guide further therapies consisting of anticoagulation, thrombolysis, or catheter-directed interventions. Data for initial, long-term, and indefinite anticoagulation, and factors that determine whether or not a patient can be treated in the outpatient setting, are reviewed and discussed.



Publication History

Article published online:
19 July 2022

© 2022. International College of Angiology. This article is published by Thieme.

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  • References

  • 1 Tsao CW, Aday AW, Almarzooq ZI. et al. Heart Disease and Stroke Statistics-2022 update: a report from the American Heart Association. Circulation 2022; 145 (08) e153-e639
  • 2 Smith SB, Geske JB, Maguire JM, Zane NA, Carter RE, Morgenthaler TI. Early anticoagulation is associated with reduced mortality for acute pulmonary embolism. Chest 2010; 137 (06) 1382-1390
  • 3 Porres-Aguilar M, Anaya-Ayala JE, Jiménez D, Mukherjee D. Pulmonary embolism response teams: pursuing excellence in the care for venous thromboembolism. Arch Med Res 2019; 50 (05) 257-258
  • 4 Porres-Aguilar M, Anaya-Ayala JE, Mukherjee D, Tapson VF. Pulmonary embolism response teams in the challenging era of venous thromboembolism associated with COVID-19. J Vasc Surg Venous Lymphat Disord 2020; 8 (05) 898-899
  • 5 Porres-Aguilar M, Jiménez D, Porres-Muñoz M, Mukherjee D. Pulmonary embolism response teams: purpose, evidence for efficacy, and future research directions. Res Pract Thromb Haemost 2019; 3 (04) 769
  • 6 Porres-Aguilar M, Tapson VF, Rivera-Lebron BN. et al. Impact and role of pulmonary embolism response teams in venous thromboembolism associated with COVID-19. J Investig Med 2021; 69 (06) 1153-1155
  • 7 Rivera-Lebron B, McDaniel M, Ahrar K. et al; PERT Consortium. Diagnosis, treatment and follow up of acute pulmonary embolism: consensus practice from the PERT Consortium. Clin Appl Thromb Hemost 2019; 25: 1076029619853037
  • 8 Robertson L, Jones LE. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for the initial treatment of venous thromboembolism. Cochrane Database Syst Rev 2017; 2: CD001100
  • 9 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
  • 10 Dawwas GK, Leonard CE, Lewis JD, Cuker A. Risk for recurrent venous thromboembolism and bleeding with apixaban compared with rivaroxaban: an analysis of real-world data. Ann Intern Med 2022; 175 (01) 20-28
  • 11 Clark NP. Role of the anticoagulant monitoring service in 2018: beyond warfarin. Hematology (Am Soc Hematol Educ Program) 2018; 2018 (01) 348-352
  • 12 Khan F, Rahman A, Carrier M. et al; MARVELOUS Collaborators. Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis. BMJ 2019; 366: l4363
  • 13 Konstantinides SV, Meyer G, Becattini C. et al; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020; 41 (04) 543-603
  • 14 Jaff MR, McMurtry MS, Archer SL. et al; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, American Heart Association Council on Peripheral Vascular Disease, American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011; 123 (16) 1788-1830
  • 15 Stevens SM, Woller SC, Baumann Kreuziger L. et al. Executive summary: antithrombotic therapy for VTE disease: second update of the CHEST Guideline and Expert Panel Report. Chest 2021; 160 (06) 2247-2259
  • 16 Chatterjee S, Chakraborty A, Weinberg I. et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA 2014; 311 (23) 2414-2421
  • 17 Jara-Palomares L, Jiménez D, Bikdeli B. et al; RIETE investigators. Derivation and validation of a clinical prediction rule for thrombolysis-associated major bleeding in patients with acute pulmonary embolism: the BACS score. Eur Respir J 2020; 20200723: 2002336
  • 18 Wang C, Zhai Z, Yang Y. et al; China Venous Thromboembolism (VTE) Study Group. Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial. Chest 2010; 137 (02) 254-262
  • 19 Matosevic B, Knoflach M, Werner P. et al. Fibrinogen degradation coagulopathy and bleeding complications after stroke thrombolysis. Neurology 2013; 80 (13) 1216-1224
  • 20 Lee VH, Conners JJ, Cutting S, Song SY, Bernstein RA, Prabhakaran S. Elevated international normalized ratio as a manifestation of post-thrombolytic coagulopathy in acute ischemic stroke. J Stroke Cerebrovasc Dis 2014; 23 (08) 2139-2144
  • 21 Results of a prospective randomized trial evaluating surgery versus thrombolysis for ischemia of the lower extremity. The STILE trial. Ann Surg 1994; 220 (03) 251-266 , discussion 266–268
  • 22 Nicholls SC, Hoffer EK, Chandler WL. Failure of peripheral arterial thrombolysis due to elevated plasminogen activator inhibitor type 1. Blood Coagul Fibrinolysis 2003; 14 (08) 729-733
  • 23 Agnelli G, Becattini C, Meyer G. et al; Caravaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med 2020; 382 (17) 1599-1607
  • 24 Raskob GE, van Es N, Verhamme P. et al; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 2018; 378 (07) 615-624
  • 25 Lee AY, Levine MN, Baker RI. et al; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349 (02) 146-153
  • 26 McBane II RD, 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 (02) 411-421
  • 27 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
  • 28 Davis KA, Davis DO. Direct acting oral anticoagulants for the treatment of suspected heparin-induced thrombocytopenia. Eur J Haematol 2017; 99 (04) 332-335
  • 29 Krauel K, Hackbarth C, Fürll B, Greinacher A. Heparin-induced thrombocytopenia: in vitro studies on the interaction of dabigatran, rivaroxaban, and low-sulfated heparin, with platelet factor 4 and anti-PF4/heparin antibodies. Blood 2012; 119 (05) 1248-1255
  • 30 Shatzel JJ, Crapster-Pregont M, Deloughery TG. Non-vitamin K antagonist oral anticoagulants for heparin-induced thrombocytopenia. A systematic review of 54 reported cases. Thromb Haemost 2016; 116 (02) 397-400
  • 31 Walenga JM, Prechel M, Jeske WP. et al. Rivaroxaban–an oral, direct factor Xa inhibitor–has potential for the management of patients with heparin-induced thrombocytopenia. Br J Haematol 2008; 143 (01) 92-99
  • 32 White RH, Brunson A, Romano PS, Li Z, Wun T. Outcomes after vena cava filter use in noncancer patients with acute venous thromboembolism: a population-based study. Circulation 2016; 133 (21) 2018-2029
  • 33 Rodriguez JJ, Munoz OC, Porres-Aguilar M, Mukherjee D. Thromboembolic complications in severe COVID-19: current antithrombotic strategies and future perspectives. Cardiovasc Hematol Disord Drug Targets 2021; 21 (01) 23-29
  • 34 Bikdeli B, Madhavan MV, Jimenez D. et al; Global COVID-19 Thrombosis Collaborative Group, Endorsed by the ISTH, NATF, ESVM, and the IUA, Supported by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol 2020; 75 (23) 2950-2973
  • 35 Zhai Z, Li C, Chen Y. et al; Prevention Treatment of VTE Associated with COVID-19 Infection Consensus Statement Group. Prevention and treatment of venous thromboembolism associated with coronavirus disease 2019 infection: a consensus statement before guidelines. Thromb Haemost 2020; 120 (06) 937-948
  • 36 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
  • 37 Schulman S, Kakkar AK, Goldhaber SZ. et al; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 2014; 129 (07) 764-772
  • 38 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
  • 39 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
  • 40 Agnelli G, Buller HR, Cohen A. et al. Oral apixaban for the treatment of venous thromboembolism in cancer patients: results from the AMPLIFY trial. J Thromb Haemost 2015; 13 (12) 2187-2191
  • 41 Levine M, Hirsh J, Weitz J. et al. A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism. Chest 1990; 98 (06) 1473-1479
  • 42 Tissue plasminogen activator for the treatment of acute pulmonary embolism. A collaborative study by the PIOPED Investigators. Chest 1990; 97 (03) 528-533
  • 43 Dalla-Volta S, Palla A, Santolicandro A. et al. PAIMS 2: alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism. Plasminogen activator Italian multicenter study 2. J Am Coll Cardiol 1992; 20 (03) 520-526
  • 44 Goldhaber SZ, Haire WD, Feldstein ML. et al. Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion. Lancet 1993; 341 (8844): 507-511
  • 45 Goldhaber SZ, Agnelli G, Levine MN. The Bolus Alteplase Pulmonary Embolism Group. Reduced dose bolus alteplase vs conventional alteplase infusion for pulmonary embolism thrombolysis. An international multicenter randomized trial. Chest 1994; 106 (03) 718-724
  • 46 Sors H, Pacouret G, Azarian R, Meyer G, Charbonnier B, Simonneau G. Hemodynamic effects of bolus vs 2-h infusion of alteplase in acute massive pulmonary embolism. A randomized controlled multicenter trial. Chest 1994; 106 (03) 712-717
  • 47 Meneveau N, Schiele F, Vuillemenot A. et al. Streptokinase vs alteplase in massive pulmonary embolism. A randomized trial assessing right heart haemodynamics and pulmonary vascular obstruction. Eur Heart J 1997; 18 (07) 1141-1148
  • 48 Tebbe U, Graf A, Kamke W. et al. Hemodynamic effects of double bolus reteplase versus alteplase infusion in massive pulmonary embolism. Am Heart J 1999; 138 (1 Pt 1): 39-44
  • 49 Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W. Management Strategies and Prognosis of Pulmonary Embolism-3 Trial Investigators. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med 2002; 347 (15) 1143-1150
  • 50 Becattini C, Agnelli G, Salvi A. et al; TIPES Study Group. Bolus tenecteplase for right ventricle dysfunction in hemodynamically stable patients with pulmonary embolism. Thromb Res 2010; 125 (03) e82-e86
  • 51 Fasullo S, Scalzo S, Maringhini G. et al. Six-month echocardiographic study in patients with submassive pulmonary embolism and right ventricle dysfunction: comparison of thrombolysis with heparin. Am J Med Sci 2011; 341 (01) 33-39
  • 52 Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M. “MOPETT” Investigators. Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” Trial). Am J Cardiol 2013; 111 (02) 273-277
  • 53 Kline JA, Nordenholz KE, Courtney DM. et al. Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double-blind, placebo-controlled randomized trial. J Thromb Haemost 2014; 12 (04) 459-468
  • 54 Meyer G, Vicaut E, Danays T. et al; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014; 370 (15) 1402-1411
  • 55 Patra S, Nagesh CM, Reddy B. et al. Thrombolysis with single bolus tenecteplase compared with streptokinase infusion in the treatment of acute pulmonary embolism: a pilot study. Clin Appl Thromb Hemost 2015; 21 (06) 550-557
  • 56 Kiser TH, Burnham EL, Clark B. et al. Half-dose versus full-dose alteplase for treatment of pulmonary embolism. Crit Care Med 2018; 46 (10) 1617-1625