avkАрхивъ внутренней медициныThe Russian Archives of Internal Medicine2226-67042411-6564“SINAPS” LLC10.20514/2226-6704-2019-9-5-348-366avk-963Research ArticleОБЗОРНЫЕ СТАТЬИREVIEW ARTICLESСОВРЕМЕННЫЕ ВЗГЛЯДЫ НА АНТИКОАГУЛЯНТНУЮ И ТРОМБОЛИТИЧЕСКУЮ ТЕРАПИЮ ОСТРОЙ ЛЕГОЧНОЙ ЭМБОЛИИCURRENT VIEW ON ANTICOAGULANT AND THROMBOLYTIC TREATMENT OF ACUTE PULMONARY EMBOLISMИгнатенкоГ. А.IgnatenkoG. A.

Донецк

Donetsk

taradin@inbox.ruТарадинГ. Г.TaradinG. G.

Геннадий Геннадьевич Тарадин

Донецк

Gennady G. Taradin

Donetsk

ВатутинН. Т.VatutinN. T.КанишеваИ. В.KanishevaI. V.ГОО ВПО «Донецкий национальный медицинский университет им. М. Горького»УкраинаState Educational Organization of Higher Professional Education «M. Gorky Donetsk National Medical University»UkraineГОО ВПО «Донецкий национальный медицинский университет им. М. Горького»; ГУ «Институт неотложной и восстановительной хирургии им. В.К. Гусака»УкраинаState Educational Organization of Higher Professional Education «M. Gorky Donetsk National Medical University»; State Institution «V.K. Gusak Institute of Urgent and Recovery Surgery»Ukraine20190610201995348366Copyright © Игнатенко Г.А., Тарадин Г.Г., Ватутин Н.Т., Канишева И.В., 20192019Игнатенко Г.А., Тарадин Г.Г., Ватутин Н.Т., Канишева И.В.Ignatenko G.A., Taradin G.G., Vatutin N.T., Kanisheva I.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medarhive.ru/jour/article/view/963

Представленный обзор посвящен современным представлениям об особенностях антикоагулянтной и тромболитической терапии венозной тромбоэмболии и, в большей степени, острой легочной эмболии. Приводится современная классификация больных с острой легочной эмболией на основе расчёта риска ранней смертности и массивности тромбоэмбологенного события. Подчеркивается важность мультидисциплинарного подхода ведения больных легочной эмболией с привлечением кардиолога, реаниматолога, пульмонолога, торакального и кардиохирурга, нацеленных на лечение легочной эмболии на всех её этапах: от клинического подозрения до выбора и осуществления любого медицинского вмешательства. Подробно освещена антикоагулянтная терапия с демонстрацией результатов крупных исследований, посвященных оценке эффективности и безопасности антикоагулянтных препаратов. Приведена характеристика, основные дозировки и схемы применения прямых (новых) антикоагулянтов, включая апиксабан, ривароксабан, дабигатран, эдоксабан и бетриксабан. Отдельно затронуты вопросы ведения больных с геморрагическими осложнениями при проведении антикоагулянтной терапии и её применения у онкологических больных, часто страдающих венозными тромбоэмболиями. Кроме того, в обзоре подробно изложены современные подходы к проведению системного тромболизиса с использованием внутривенно вводимых препаратов: стрептокиназы, урокиназы и тканевых активаторов плазминогена. Описываются показания, противопоказания, результаты клинических исследований, посвященных различным режимам тромболитической терапии, включая лечение легочной эмболии пониженными дозировками фибринолитиков.

The presented review concerns contemporary views on specific aspects of anticoagulant and thrombolytic treatment of venous thromboembolism and mostly of acute pulmonary embolism. Modern classifications of patients with acute pulmonary embolism, based on early mortality risk and severity of thromboembolic event, are reproduced. The importance of multidisciplinary approach to the management of patients with pulmonary embolism with the assistance of cardiologist, intensive care specialist, pulmonologist, thoracic and cardiovascular surgeon, aimed at the management of pulmonary embolism at all stages: from clinical suspicion to the selection and performing of any medical intervention, is emphasized. Anticoagulant treatment with the demonstration of results of major trials, devoted to efficacy and safety evaluation of anticoagulants, is highlighted in details. Moreover, characteristics, basic dosage and dosage scheme of direct (new) oral anticoagulants, including apixaban, rivaroxaban, dabigatran, edoxaban and betrixaban are described in the article. In particular, the management of patients with bleeding complications of anticoagulant treatment and its application in cancer patients, who often have venous thromboembolism, is described. Additionally, modern approaches to systemic thrombolysis with intravenous streptokinase, urokinase and tissue plasminogen activators are presented in this review. The indications, contraindications, results of clinical trials devoted to various regimens of thrombolytic therapy, including treatment of pulmonary embolism by lower doses of fibrinolytic agents, are described.

легочная эмболиявенозная тромбоэмболиятромбоэмболия легочной артериилечениестратификация рискаантикоагулянтная терапияпрямые оральные антикоагулянтысистемный тромболизисфибринолизгеморрагические осложненияpulmonary embolismvenous thromboembolismthromboembolism of pulmonary arterytreatmentrisk stratificationanticoagulant therapydirect oral anticoagulantssystemic thrombolysisfibrinolysisbleeding complicationsReferencesKonstantinides S.V., Torbicki A., Agnelli G., et al. 2014 ESC 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) endorsed by the european respiratory society (ERS). European Heart Journal. 2014; 35(43): 3033–69, 3069a-3069k. DOI:10.1093/eurheartj/ehu283.Konstantinides S.V., Torbicki A., Agnelli G., et al. 2014 ESC 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) endorsed by the european respiratory society (ERS). European Heart Journal. 2014; 35(43): 3033–69, 3069a-3069k. DOI:10.1093/eurheartj/ehu283.Tritschler T, Kraaijpoel N, Le Gal G, Wells PS. Venous thromboembolism: advances in diagnosis and treatment. JAMA. 2018 Oct 16;320(15):1583-1594. doi: 10.1001/jama.2018.14346.Tritschler T, Kraaijpoel N, Le Gal G, Wells PS. Venous thromboembolism: advances in diagnosis and treatment. JAMA. 2018 Oct 16;320(15):1583-1594. doi: 10.1001/jama.2018.14346.Tagalakis V, Patenaude V, Kahn SR, Suissa S. Incidence of and mortality from venous thromboembolism in a real-world population: the Q-VTE Study Cohort. Am J Med. 2013;126(9): 832.e13-832. doi:10.1016/j.amjmed.2013.02.024Tagalakis V, Patenaude V, Kahn SR, Suissa S. Incidence of and mortality from venous thromboembolism in a real-world population: the Q-VTE Study Cohort. Am J Med. 2013;126(9): 832.e13-832. doi:10.1016/j.amjmed.2013.02.024Konstantinides S.V., Barco S., Lankeit M., Meyer G. Management of pulmonary embolism: an update. J Am Coll Cardiol. 2016 Mar 1;67(8):976-90. doi: 10.1016/j.jacc.2015.11.061.Konstantinides S.V., Barco S., Lankeit M., Meyer G. Management of pulmonary embolism: an update. J Am Coll Cardiol. 2016 Mar 1;67(8):976-90. doi: 10.1016/j.jacc.2015.11.061.Carrier M, Righini M, Wells PS, et al. Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications: a systematic review and meta-analysis of the management outcome studies. J Thromb Haemost. 2010;8(8):1716-1722. doi:10.1111/j.1538-7836.2010.03938.xCarrier M, Righini M, Wells PS, et al. Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications: a systematic review and meta-analysis of the management outcome studies. J Thromb Haemost. 2010;8(8):1716-1722. doi:10.1111/j.1538-7836.2010.03938.xВатутин Н.Т., Тарадин Г.Г., Канишева И.В. и др. Роль интервенционных методов в лечении острой легочной эмболии. Архивъ внутренней медицины. 2018; 8(5):346-360. doi: 10.20514/22266704-2018-0-5-346-360.Vatutin N.T., Taradin G.G., Kanisheva I.V., et al. The role of interventional methods in treatment of pulmonary embolism. The Russian Archives of Internal Medicine. 2018;8(5):346-360. [In Russian] doi: 10.20514/2226-6704-2018-0-5-346-360Torbicki A, Perrier A, Konstantinides S, et al.; ESC Committee for Practice Guidelines (CPG). 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 Sep;29(18):2276-315. doi: 10.1093/eurheartj/ehn310.Torbicki A, Perrier A, Konstantinides S, et al.; ESC Committee for Practice Guidelines (CPG). 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 Sep;29(18):2276-315. doi: 10.1093/eurheartj/ehn310.Jaff M.R., McMurtry M.S., Archer S.L., et al. 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):1788-830. doi: 10.1161/CIR.0b013e318214914f.Jaff M.R., McMurtry M.S., Archer S.L., et al. 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):1788-830. doi: 10.1161/CIR.0b013e318214914f.Sekhri V, Mehta N, Rawat N, et al. Management of massive and nonmassive pulmonary embolism. Arch Med Sci. 2012 Dec 20; 8(6):957-69. doi: 10.5114/aoms.2012.32402.Sekhri V, Mehta N, Rawat N, et al. Management of massive and nonmassive pulmonary embolism. Arch Med Sci. 2012 Dec 20; 8(6):957-69. doi: 10.5114/aoms.2012.32402.Bĕlohlavek J, Dytrych V, Linhart A. Pulmonary embolism, part I: Epidemiology, risk factors and risk stratification, pathophysiology, clinical presentation, diagnosis and nonthrombotic pulmonary embolism. Exp Clin Cardiol. 2013 Spring;18(2):129-38.Bĕlohlavek J, Dytrych V, Linhart A. Pulmonary embolism, part I: Epidemiology, risk factors and risk stratification, pathophysiology, clinical presentation, diagnosis and nonthrombotic pulmonary embolism. Exp Clin Cardiol. 2013 Spring;18(2):129-38.Corrigan D, Prucnal C, Kabrhel C. Pulmonary embolism: the diagnosis, risk-stratification, treatment and disposition of emergency department patients. Clin Exp Emerg Med. 2016 Sep; 3(3): 117–125. doi: 10.15441/ceem.16.146Corrigan D, Prucnal C, Kabrhel C. Pulmonary embolism: the diagnosis, risk-stratification, treatment and disposition of emergency department patients. Clin Exp Emerg Med. 2016 Sep; 3(3): 117–125. doi: 10.15441/ceem.16.146Miller G.A., Sutton G.C., Kerr I.H., et al. Comparison of streptokinase and heparin in treatment of isolated acute massive pulmonary embolism. Br Med J. 1971;2:681– 684.Miller G.A., Sutton G.C., Kerr I.H., et al. Comparison of streptokinase and heparin in treatment of isolated acute massive pulmonary embolism. Br Med J. 1971;2:681– 684.Aujesky D., Obrosky D.S., Stone R.A., et al. Derivation and validation of a prognostic model for pulmonary embolism. Am. J. Respir. Crit. Care Med. 2005;172: 1041–1046.Aujesky D., Obrosky D.S., Stone R.A., et al. Derivation and validation of a prognostic model for pulmonary embolism. Am. J. Respir. Crit. Care Med. 2005;172: 1041–1046.Jimenez 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 Aug 9;170(15):1383-9. doi: 10.1001/archinternmed.2010.199Jimenez 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 Aug 9;170(15):1383-9. doi: 10.1001/archinternmed.2010.199Huisman M.V., Barco S., Cannegieter S.C., et al. Pulmonary embolism. Nat. Rev. Dis. Primers. 2018 May 17;4:18028. doi: 10.1038/nrdp.2018.28.Huisman M.V., Barco S., Cannegieter S.C., et al. Pulmonary embolism. Nat. Rev. Dis. Primers. 2018 May 17;4:18028. doi: 10.1038/nrdp.2018.28.Kabrhel C., Jaff M.R., Channick R.N., et al. A multidisciplinary pulmonary embolism response team. CHEST Journal. 2013; 144(5):1738-1739.Kabrhel C., Jaff M.R., Channick R.N., et al. A multidisciplinary pulmonary embolism response team. CHEST Journal. 2013; 144(5):1738-1739.Root C.W., Dudzinski D.M., Zakhary B., et al. Multidisciplinary approach to the management of pulmonary embolism patients: the pulmonary embolism response team (PERT). J Multidiscip Healthc. 2018 Apr 5;11:187-195. doi: 10.2147/JMDH.S151196.Root C.W., Dudzinski D.M., Zakhary B., et al. Multidisciplinary approach to the management of pulmonary embolism patients: the pulmonary embolism response team (PERT). J Multidiscip Healthc. 2018 Apr 5;11:187-195. doi: 10.2147/JMDH.S151196.Petriş AO, Konstantinides S, Tint D, et al. Therapeutic advances in emergency cardiology: acute pulmonary embolism. Am J Ther. 2019 Mar/Apr;26(2):e248-e256. doi: 10.1097/MJT.0000000000000917.Petriş AO, Konstantinides S, Tint D, et al. Therapeutic advances in emergency cardiology: acute pulmonary embolism. Am J Ther. 2019 Mar/Apr;26(2):e248-e256. doi: 10.1097/MJT.0000000000000917.Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism. Lancet 1960;275(7138):1309–12.Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism. Lancet 1960;275(7138):1309–12.Jolly M., Phillips J. Pulmonary embolism: current role of catheter treatment options and operative thrombectomy. Surg. Clin. North. Am. 2018 Apr;98(2):279-292. doi: 10.1016/j.suc.2017.11.009.Jolly M., Phillips J. Pulmonary embolism: current role of catheter treatment options and operative thrombectomy. Surg. Clin. North. Am. 2018 Apr;98(2):279-292. doi: 10.1016/j.suc.2017.11.009.Chopard R, Andarelli JN, Humbert S, et al. Prescription patterns of direct oral anticoagulants in pulmonary embolism: A prospective multicenter French registry. Thromb Res. 2019 Feb;174:27-33. doi: 10.1016/j.thromres.2018.12.013.Chopard R, Andarelli JN, Humbert S, et al. Prescription patterns of direct oral anticoagulants in pulmonary embolism: A prospective multicenter French registry. Thromb Res. 2019 Feb;174:27-33. doi: 10.1016/j.thromres.2018.12.013.Stein PD, Dalen JE, Matta F, et al. Optimal therapy for unstable pulmonary embolism. Am J Med. 2019 Feb;132(2):168-171. doi: 10.1016/j.amjmed.2018.09.018.Stein PD, Dalen JE, Matta F, et al. Optimal therapy for unstable pulmonary embolism. Am J Med. 2019 Feb;132(2):168-171. doi: 10.1016/j.amjmed.2018.09.018.Borohovitz A, Weinberg MD, Weinberg I. Pulmonary embolism: Care standards in 2018. Prog Cardiovasc Dis. 2018 Mar — Apr;60(6):613621. doi: 10.1016/j.pcad.2017.12.005.Borohovitz A, Weinberg MD, Weinberg I. Pulmonary embolism: Care standards in 2018. Prog Cardiovasc Dis. 2018 Mar — Apr;60(6):613621. doi: 10.1016/j.pcad.2017.12.005.Hepburn-Brown M, Darvall J, Hammerschlag G. Acute pulmonary embolism: a concise review of diagnosis and management. Intern Med J. 2019 Jan;49(1):15-27. doi: 10.1111/imj.14145Hepburn-Brown M, Darvall J, Hammerschlag G. Acute pulmonary embolism: a concise review of diagnosis and management. Intern Med J. 2019 Jan;49(1):15-27. doi: 10.1111/imj.14145Kearon C, AgenoW, Cannegieter SC, et al.; Subcommittees on Control of Anticoagulation, and Predictive and Diagnostic Variables in Thrombotic Disease. Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH. J Thromb Haemost. 2016;14(7):1480-1483. doi:10.1111/jth.13336Kearon C, AgenoW, Cannegieter SC, et al.; Subcommittees on Control of Anticoagulation, and Predictive and Diagnostic Variables in Thrombotic Disease. Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH. J Thromb Haemost. 2016;14(7):1480-1483. doi:10.1111/jth.13336Carrier M., Le G.G., Wells P.S., et al. Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann. Intern. Med. 2010 May 4;152(9):578-89. doi: 10.7326/0003-4819-152-9201005040-00008.Carrier M., Le G.G., Wells P.S., et al. Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann. Intern. Med. 2010 May 4;152(9):578-89. doi: 10.7326/0003-4819-152-9201005040-00008.Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv. 2018 Nov 27;2(22):3257-3291. doi: 10.1182/bloodadvances.2018024893.Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv. 2018 Nov 27;2(22):3257-3291. doi: 10.1182/bloodadvances.2018024893.Kearon C., Akl E.A., Ornelas J., et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315-352. doi: 10.1016/j.chest.2015.11.026.Kearon C., Akl E.A., Ornelas J., et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315-352. doi: 10.1016/j.chest.2015.11.026.Heidbuchel H., Verhamme P., Alings M., et al. EHRA practical guide on the use of new oral anticoagulants in patients with nonvalvular atrial fibrillation: executive summary. Eur Heart J. 2013 Jul; 34(27): 20942106. doi: 10.1093/eurheartj/eht134.Heidbuchel H., Verhamme P., Alings M., et al. EHRA practical guide on the use of new oral anticoagulants in patients with nonvalvular atrial fibrillation: executive summary. Eur Heart J. 2013 Jul; 34(27): 20942106. doi: 10.1093/eurheartj/eht134.Beyer-Westendorf J., Verhamme P., Bauersachs R. Betrixaban for prevention of venous thromboembolism in acute medically ill patients. Eur Heart J Suppl. 2018 May;20(Suppl E):E16-E22. doi: 10.1093/eurheartj/suy017Beyer-Westendorf J., Verhamme P., Bauersachs R. Betrixaban for prevention of venous thromboembolism in acute medically ill patients. Eur Heart J Suppl. 2018 May;20(Suppl E):E16-E22. doi: 10.1093/eurheartj/suy017van Es N., Coppens M., Schulman S., et al. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 2014; Sep 18; 124(12):1968-75. doi: 10.1182/blood-2014-04-571232.van Es N., Coppens M., Schulman S., et al. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 2014; Sep 18; 124(12):1968-75. doi: 10.1182/blood-2014-04-571232.van der Hulle T., Kooiman J., den Exter P.L., et al. Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J. Thromb. Haemost. 2014;12(3):320-8. doi: 10.1111/jth.12485.van der Hulle T., Kooiman J., den Exter P.L., et al. Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J. Thromb. Haemost. 2014;12(3):320-8. doi: 10.1111/jth.12485.Arcadi FA, Portaro S, Giorgianni R, et al. New versus old oral anticoagulants: how can we set the scale needle? Considerations on a case report. Medicina (Kaunas). 2019 Mar 17;55(3). pii: E71. doi: 10.3390/medicina55030071Arcadi FA, Portaro S, Giorgianni R, et al. New versus old oral anticoagulants: how can we set the scale needle? Considerations on a case report. Medicina (Kaunas). 2019 Mar 17;55(3). pii: E71. doi: 10.3390/medicina55030071Dawwas GK, Brown J, Dietrich E, et al. Effectiveness and safety of apixaban versus rivaroxaban for prevention of recurrent venous thromboembolism and adverse bleeding events in patients with venous thromboembolism: a retrospective population-based cohort analysis. Lancet Haematol. 2019 Jan;6(1):e20-e28. doi: 10.1016/S23523026(18)30191-1.Dawwas GK, Brown J, Dietrich E, et al. Effectiveness and safety of apixaban versus rivaroxaban for prevention of recurrent venous thromboembolism and adverse bleeding events in patients with venous thromboembolism: a retrospective population-based cohort analysis. Lancet Haematol. 2019 Jan;6(1):e20-e28. doi: 10.1016/S23523026(18)30191-1.Schulman S., Kearon C., Kakkar A.K., et al.; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342-52. doi: 10.1056/NEJMoa0906598.Schulman S., Kearon C., Kakkar A.K., et al.; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342-52. doi: 10.1056/NEJMoa0906598.Schulman S., Kakkar A.K., Goldhaber S.Z., et al.; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014;129(7):764-72. doi: 10.1161/CIRCULATIONAHA.113.004450Schulman S., Kakkar A.K., Goldhaber S.Z., et al.; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014;129(7):764-72. doi: 10.1161/CIRCULATIONAHA.113.004450Bauersachs R., Berkowitz S.D., Brenner B., et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499-510. doi: 10.1056/NEJMoa1007903.Bauersachs R., Berkowitz S.D., Brenner B., et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499-510. doi: 10.1056/NEJMoa1007903.Buller H.R., Prins M.H., Lensin A.W., et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287-97. doi: 10.1056/NEJMoa1113572Buller H.R., Prins M.H., Lensin A.W., et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287-97. doi: 10.1056/NEJMoa1113572Agnelli G., Buller H.R., Cohen A., et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9):799-808. doi: 10.1056/NEJMoa1302507.Agnelli G., Buller H.R., Cohen A., et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9):799-808. doi: 10.1056/NEJMoa1302507.Buller H.R., Decousus H., Grosso M.A., et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369(15):1406-15. doi: 10.1056/NEJMoa1306638.Buller H.R., Decousus H., Grosso M.A., et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369(15):1406-15. doi: 10.1056/NEJMoa1306638.Martin K., Beyer-Westendorf J., Davidson B.L., et al. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J. Thromb. Haemost. 2016 Jun;14(6):1308-13. doi: 10.1111/jth.13323.Martin K., Beyer-Westendorf J., Davidson B.L., et al. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J. Thromb. Haemost. 2016 Jun;14(6):1308-13. doi: 10.1111/jth.13323.Piran S, Schulman S. Treatment of bleeding complications in patients on anticoagulant therapy. Blood. 2019;133(5):425-435. doi:10.1182/blood-2018-06-820746Piran S, Schulman S. Treatment of bleeding complications in patients on anticoagulant therapy. Blood. 2019;133(5):425-435. doi:10.1182/blood-2018-06-820746Shakur H, Roberts I, Bautista R, et al.; CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010; 376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5.Shakur H, Roberts I, Bautista R, et al.; CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010; 376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5.Douxfils J, Gosselin RC. Laboratory assessment of direct oral anticoagulants. Semin Thromb Hemost. 2017 Apr;43(3):277-290. doi: 10.1055/s-0036-1597296Douxfils J, Gosselin RC. Laboratory assessment of direct oral anticoagulants. Semin Thromb Hemost. 2017 Apr;43(3):277-290. doi: 10.1055/s-0036-1597296Mosarla RC, Vaduganathan M, Qamar A, et al. Anticoagulation strategies in patients with cancer: JACC Review Topic of the Week. J Am Coll Cardiol. 2019 Mar 26;73(11):1336-1349. doi: 10.1016/j.jacc.2019.01.017Mosarla RC, Vaduganathan M, Qamar A, et al. Anticoagulation strategies in patients with cancer: JACC Review Topic of the Week. J Am Coll Cardiol. 2019 Mar 26;73(11):1336-1349. doi: 10.1016/j.jacc.2019.01.017Lee AY, Levine MN, Baker RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10; 349(2):146-53.Lee AY, Levine MN, Baker RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10; 349(2):146-53.Lee AYY, Kamphuisen PW, Meyer G, et al.; CATCH Investigators.. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: a randomized clinical trial. JAMA. 2015 Aug 18;314(7):677-686. doi: 10.1001/jama.2015.9243.Lee AYY, Kamphuisen PW, Meyer G, et al.; CATCH Investigators.. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: a randomized clinical trial. JAMA. 2015 Aug 18;314(7):677-686. doi: 10.1001/jama.2015.9243.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; 378:615–24. doi: 10.1056/NEJMoa1711948Raskob 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; 378:615–24. doi: 10.1056/NEJMoa1711948Young A, Marshall A, Thirlwall J, et al. Anticoagulation therapy in selected cancer patients at risk of recurrence of venous thromboembolism: results of the Select-D Pilot Trial. Blood 2017; 130:625.Young A, Marshall A, Thirlwall J, et al. Anticoagulation therapy in selected cancer patients at risk of recurrence of venous thromboembolism: results of the Select-D Pilot Trial. Blood 2017; 130:625.Li A, Garcia DA, Lyman GH, et al. Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): A systematic review and meta-analysis. Thromb Res 2018: doi:10.1016/j.thromres.2018.02.144.Li A, Garcia DA, Lyman GH, et al. Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): A systematic review and meta-analysis. Thromb Res 2018: doi:10.1016/j.thromres.2018.02.144.Peacock WF, Singer AJ. Reducing the hospital burden associated with the treatment of pulmonary embolism. J Thromb Haemost. 2019 Mar 9. doi: 10.1111/jth.14423Peacock WF, Singer AJ. Reducing the hospital burden associated with the treatment of pulmonary embolism. J Thromb Haemost. 2019 Mar 9. doi: 10.1111/jth.14423Khorana AA, Noble S, Lee AYY, et al. Role of direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism: guidance from the SSC of the ISTH. J Thromb Haemost 2018 Sep;16(9):1891-1894. doi: 10.1111/jth.14219.Khorana AA, Noble S, Lee AYY, et al. Role of direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism: guidance from the SSC of the ISTH. J Thromb Haemost 2018 Sep;16(9):1891-1894. doi: 10.1111/jth.14219.Bartel B. Systemic thrombolysis for acute pulmonary embolism. Hosp. Pract. 2015;43(1):22-7. doi: 10.1080/21548331.2015.1001302.Bartel B. Systemic thrombolysis for acute pulmonary embolism. Hosp. Pract. 2015;43(1):22-7. doi: 10.1080/21548331.2015.1001302.Konstantinides S.V., Barco S. Systemic thrombolytic therapy for acute pulmonary embolism: who is a candidate? Semin. Respir. Crit. Care Med. 2017 Feb;38(1):56-65. doi: 10.1055/s-0036-1597560.Konstantinides S.V., Barco S. Systemic thrombolytic therapy for acute pulmonary embolism: who is a candidate? Semin. Respir. Crit. Care Med. 2017 Feb;38(1):56-65. doi: 10.1055/s-0036-1597560.Marti C., John G., Konstantinides S., et al. Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis. Eur Heart J 2015; 36(10):605-14. doi: 10.1093/eurheartj/ehu218.Marti C., John G., Konstantinides S., et al. Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis. Eur Heart J 2015; 36(10):605-14. doi: 10.1093/eurheartj/ehu218.Stein P.D., Matta F. Thrombolytic therapy in unstable patients with acute pulmonary embolism: saves lives but underused. Am J Med. 2012; 125(5):465-70. doi: 10.1016/j.amjmed.2011.10.015.Stein P.D., Matta F. Thrombolytic therapy in unstable patients with acute pulmonary embolism: saves lives but underused. Am J Med. 2012; 125(5):465-70. doi: 10.1016/j.amjmed.2011.10.015.Murphy E, Lababidi A, Reddy R, et al. The role of thrombolytic therapy for patients with a submassive pulmonary embolism. Cureus. 2018;10(6):e2814. doi:10.7759/cureus.2814Murphy E, Lababidi A, Reddy R, et al. The role of thrombolytic therapy for patients with a submassive pulmonary embolism. Cureus. 2018;10(6):e2814. doi:10.7759/cureus.2814Virk HUH, Chatterjee S, Sardar P, et al. Systemic thrombolysis for pulmonary embolism: evidence, patient selection, and protocols for management. Interv Cardiol Clin. 2018 Jan;7(1):71-80. doi: 10.1016/j.iccl.2017.08.001.Virk HUH, Chatterjee S, Sardar P, et al. Systemic thrombolysis for pulmonary embolism: evidence, patient selection, and protocols for management. Interv Cardiol Clin. 2018 Jan;7(1):71-80. doi: 10.1016/j.iccl.2017.08.001.Никитина О.В., Михайлов И.П., Кудряшова Н.Е. и др. Тромболитическая и антикоагулянтная терапия при тромбоэмболии легочной артерии: влияние на легочную перфузию (часть 2). Журнал им. Н.В. Склифосовского Неотложная медицинская помощь. 2018; 7(2): 134–143. DOI: 10.23934/2223-9022-2018-7-2-134-143.Nikitina O.V., Mikhailov I.P., Kudryashova N.Y., et al. Thrombolytic and anticoagulant therapy for pulmonary embolism: an effect on pulmonary perfusion (part 2). Russian Sklifosovsky Journal of Emergency Medical Care. 2018; 7(2): 134–143. DOI: 10.23934/2223-9022-2018-72-134-143 [in Russian].Becattini C, Agnelli G, Salvi A, et al. Bolus tenecteplase for right ventricle dysfunction in hemodynamically stable patients with pulmonary embolism. Thromb Res. 2010;125(3):e82–e86. doi: 10.1016/j.thromres.2009.09.017Becattini C, Agnelli G, Salvi A, et al. Bolus tenecteplase for right ventricle dysfunction in hemodynamically stable patients with pulmonary embolism. Thromb Res. 2010;125(3):e82–e86. doi: 10.1016/j.thromres.2009.09.017Jerjes-Sanchez C, Ramirez-Rivera A, de Lourdes Garcia M, et al. Streptokinase and heparin versus heparin alone in massive pulmonary embolism: a randomized controlled trial. J Thromb Thrombolysis. 1995;2(3):227-229.Jerjes-Sanchez C, Ramirez-Rivera A, de Lourdes Garcia M, et al. Streptokinase and heparin versus heparin alone in massive pulmonary embolism: a randomized controlled trial. J Thromb Thrombolysis. 1995;2(3):227-229.Kline J.A., Steuerwald M.T., Marchick M.R., et al. Prospective evaluation of right ventricular function and functional status 6 months after acute submassive pulmonary embolism: frequency of persistent or subsequent elevation in estimated pulmonary artery pressure. Chest 2009;136:1202-10.Kline J.A., Steuerwald M.T., Marchick M.R., et al. Prospective evaluation of right ventricular function and functional status 6 months after acute submassive pulmonary embolism: frequency of persistent or subsequent elevation in estimated pulmonary artery pressure. Chest 2009;136:1202-10.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 Jun 18; 311(23):2414-21. doi: 10.1001/jama.2014.5990Chatterjee 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 Jun 18; 311(23):2414-21. doi: 10.1001/jama.2014.5990Bougouin W., Marijon E., Planquette B., et al.; on behalf from the Sudden Death Expertise Center. Pulmonary embolism related sudden cardiac arrest admitted alive at hospital: Management and outcomes. Resuscitation. 2017;115:135-140. doi: 10.1016/j.resuscitation.2017.04.019.Bougouin W., Marijon E., Planquette B., et al.; on behalf from the Sudden Death Expertise Center. Pulmonary embolism related sudden cardiac arrest admitted alive at hospital: Management and outcomes. Resuscitation. 2017;115:135-140. doi: 10.1016/j.resuscitation.2017.04.019.Zuin M, Rigatelli G, Carraro M, et al. Systemic thrombolysis in haemodynamically unstable pulmonary embolism: The earlier the better? Thromb Res. 2019 Jan;173:117-123. doi: 10.1016/j.thromres.2018.11.029.Zuin M, Rigatelli G, Carraro M, et al. Systemic thrombolysis in haemodynamically unstable pulmonary embolism: The earlier the better? Thromb Res. 2019 Jan;173:117-123. doi: 10.1016/j.thromres.2018.11.029.Fernandes CJCDS, Jardim CVP, Alves JL Jr, et al. Reperfusion in acute pulmonary thromboembolism. J Bras Pneumol. 2018 Jun 7:0. doi: 10.1590/S1806-37562017000000204.Fernandes CJCDS, Jardim CVP, Alves JL Jr, et al. Reperfusion in acute pulmonary thromboembolism. J Bras Pneumol. 2018 Jun 7:0. doi: 10.1590/S1806-37562017000000204.Becattini C., Agnelli G., Lankeit M., et al. Acute pulmonary embolism: mortality prediction by the 2014 European Society of Cardiology risk stratification model. Eur. Respir. J. 2016;48(3):780-6. doi: 10.1183/13993003.00024-2016.Becattini C., Agnelli G., Lankeit M., et al. Acute pulmonary embolism: mortality prediction by the 2014 European Society of Cardiology risk stratification model. Eur. Respir. J. 2016;48(3):780-6. doi: 10.1183/13993003.00024-2016.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 Apr;12(4):459-68. doi: 10.1111/jth.12521.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 Apr;12(4):459-68. doi: 10.1111/jth.12521.Konstantinides S., Geibel A., Heusel G., et al.; 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 Oct 10; 347(15):1143-50.Konstantinides S., Geibel A., Heusel G., et al.; 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 Oct 10; 347(15):1143-50.Sharifi M., Bay C., Skrocki L., et al.; “MOPETT” Investigators. Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” Trial). Am J Cardiol. 2013;111(2):273-7. doi: 10.1016/j.amjcard.2012.09.027.Sharifi M., Bay C., Skrocki L., et al.; “MOPETT” Investigators. Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” Trial). Am J Cardiol. 2013;111(2):273-7. doi: 10.1016/j.amjcard.2012.09.027.Riva N., Puljak L., Moja L., et al. Multiple overlapping systematic reviews facilitate the origin of disputes: the case of thrombolytic therapy for pulmonary embolism. J Clin Epidemiol. 2018;97:1-13. doi: 10.1016/j.jclinepi.2017.11.012.Riva N., Puljak L., Moja L., et al. Multiple overlapping systematic reviews facilitate the origin of disputes: the case of thrombolytic therapy for pulmonary embolism. J Clin Epidemiol. 2018;97:1-13. doi: 10.1016/j.jclinepi.2017.11.012.Teleb M, Porres-Aguilar M, Anaya-Ayala JE, et al. Potential role of systemic thrombolysis in acute submassive intermediate risk pulmonary embolism: review and future perspectives. Ther Adv Cardiovasc Dis. 2016;10(2):103–110. doi:10.1177/1753944716630694Teleb M, Porres-Aguilar M, Anaya-Ayala JE, et al. Potential role of systemic thrombolysis in acute submassive intermediate risk pulmonary embolism: review and future perspectives. Ther Adv Cardiovasc Dis. 2016;10(2):103–110. doi:10.1177/1753944716630694Meyer G., Vicaut E., Danays T., et al.; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014; 370(15):1402-11. doi: 10.1056/NEJMoa1302097.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):1402-11. doi: 10.1056/NEJMoa1302097.Miranda CH. Use of thrombolytic agents in the treatment of acute pulmonary thromboembolism: things are not as simple as you might think. J Bras Pneumol. 2019 Feb 11;45(1):e20180297. doi: 10.1590/1806-3713/e20180297.Miranda CH. Use of thrombolytic agents in the treatment of acute pulmonary thromboembolism: things are not as simple as you might think. J Bras Pneumol. 2019 Feb 11;45(1):e20180297. doi: 10.1590/1806-3713/e20180297.Klok F.A., Dzikowska-Diduch O., Kostrubiec M., et al. Derivation of a clinical prediction score for chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. J. Thromb. Haemost. 2016;14(1):121-8. doi: 10.1111/jth.13175Klok F.A., Dzikowska-Diduch O., Kostrubiec M., et al. Derivation of a clinical prediction score for chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. J. Thromb. Haemost. 2016;14(1):121-8. doi: 10.1111/jth.13175Goldhaber S.Z. PEITHO Long-Term Outcomes Study: Data Disrupt Dogma. J Am Coll Cardiol. 2017 Mar 28;69(12):1545-1548. doi: 10.1016/j.jacc.2017.01.027.Goldhaber S.Z. PEITHO Long-Term Outcomes Study: Data Disrupt Dogma. J Am Coll Cardiol. 2017 Mar 28;69(12):1545-1548. doi: 10.1016/j.jacc.2017.01.027.Konstantinides S.V., Vicaut E., Danays T., et al. Impact of thrombolytic therapy on the long-term outcome of intermediate-risk pulmonary embolism. J Am Coll Cardiol. 2017;69(12):1536-1544. doi: 10.1016/j.jacc.2016.12.039.Konstantinides S.V., Vicaut E., Danays T., et al. Impact of thrombolytic therapy on the long-term outcome of intermediate-risk pulmonary embolism. J Am Coll Cardiol. 2017;69(12):1536-1544. doi: 10.1016/j.jacc.2016.12.039.Jimenez D, de Miguel-Diez J, Guijarro R, et al; RIETE Investigators. Trends in the management and outcomes of acute pulmonary embolism: analysis from the RIETE Registry. J Am Coll Cardiol. 2016;67(2):162–170 doi: 10.1016/j.jacc.2015.10.060.Jimenez D, de Miguel-Diez J, Guijarro R, et al; RIETE Investigators. Trends in the management and outcomes of acute pulmonary embolism: analysis from the RIETE Registry. J Am Coll Cardiol. 2016;67(2):162–170 doi: 10.1016/j.jacc.2015.10.060.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; Feb;137(2):254-62. doi: 10.1378/chest.09-0765.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; Feb;137(2):254-62. doi: 10.1378/chest.09-0765.Kiser TH, Burnham EL, Clark B, et al. Half-dose versus full-dose alteplase for treatment of pulmonary embolism. Crit Care Med. 2018 Oct;46(10):1617-1625. doi: 10.1097/CCM.0000000000003288.Kiser TH, Burnham EL, Clark B, et al. Half-dose versus full-dose alteplase for treatment of pulmonary embolism. Crit Care Med. 2018 Oct;46(10):1617-1625. doi: 10.1097/CCM.0000000000003288.Jin Q, Luo Q, Zhao Z, et al. Half-dose versus full-dose alteplase therapy in pulmonary embolism: does half dose really lose? Crit Care Med. 2018 Dec;46(12):e1223-e1224. doi: 10.1097/CCM.0000000000003384Jin Q, Luo Q, Zhao Z, et al. Half-dose versus full-dose alteplase therapy in pulmonary embolism: does half dose really lose? Crit Care Med. 2018 Dec;46(12):e1223-e1224. doi: 10.1097/CCM.0000000000003384Rothschild DP, Goldstein JA, Bowers TR. Low-dose systemic thrombolytic therapy for treatment of submassive pulmonary embolism: Clinical efficacy but attendant hemorrhagic risks. Catheter Cardiovasc Interv. 2019 Feb 15;93(3):506-510. doi: 10.1002/ccd.28042.Rothschild DP, Goldstein JA, Bowers TR. Low-dose systemic thrombolytic therapy for treatment of submassive pulmonary embolism: Clinical efficacy but attendant hemorrhagic risks. Catheter Cardiovasc Interv. 2019 Feb 15;93(3):506-510. doi: 10.1002/ccd.28042.Halaby R, Giri J. Keep it simple? Half-dose systemic thrombolysis or catheter-directed thrombolysis for pulmonary embolism. Vasc Med. 2019 Mar 5:1358863X18824653. doi: 10.1177/1358863X18824653.Halaby R, Giri J. Keep it simple? Half-dose systemic thrombolysis or catheter-directed thrombolysis for pulmonary embolism. Vasc Med. 2019 Mar 5:1358863X18824653. doi: 10.1177/1358863X18824653.

The authors declare that there are no conflicts of interest present.