Effectiveness of thrombolytic therapy in patients with severe COVID-19 and pulmonary embolism
DOI:
https://doi.org/10.61751/bmbr/3.2024.50Keywords:
thrombolysis, acute respiratory distress syndrome, alteplase, unfractionated heparinAbstract
Current research provides insufficient data on the use of thrombolytic therapy in the treatment of pulmonary embolism in patients with COVID-19. Existing studies present data on the efficacy of thrombolytic drug therapy for thrombotic complications in severe COVID-19. However, these studies either involve a very small number of observations or remain incomplete. This article aimed to assess systemic thrombolysis’s effectiveness in intravenous alteplase administration in this pathology. The medical records of 92 patients were analysed. Patients were divided into four groups depending on the therapy administered. Patients in the first group had complications in the form of pulmonary embolism but did not require thrombolytic therapy. Treatment of patients in the first group consisted of prescribing
low-molecular-weight heparin at a therapeutic dose. Patients in the second and third groups had pulmonary embolism in the context of COVID-19 and required thrombolytic therapy. The third group differed from the second in the presence of a thrombus in the right heart. Patients in the fourth group had complications in the form of pulmonary embolism, and
required thrombolytic therapy, but did not receive it due to a lack of funds. Patients in the second and third groups were immediately treated with unfractionated heparin and alteplase. Thrombolysis was not performed in the fourth group. Mortality rates were studied according to the assigned group. It was established that the risk of death increased (p<0.001)
with increasing levels of D-dimer and decreased with increasing PaO2/FiO2 (p < 0.001). In the presence of a thrombus in the right heart chambers, the risk of death increased (p = 0.002), OR = 3.97 (95% CI 1.66-9.49). A trend towards reducing death risk with thrombolytic therapy was observed (p = 0.052). Data were summarised regarding the increased (p = 0.009)
risk of death when thrombolytic therapy was delayed. Mortality in the fourth group was 100%. The obtained data indicate the significant effectiveness of thrombolytic therapy in the treatment of this pathology
Received: 01.05.2024 | Revised: 17.07.2024 | Accepted: 30.08.2024
References
Wang Y, Lu X, Li Y, Chen H, Chen T, Su N, et al. Clinical course and outcomes of 344 intensive care patients with COVID-19. Am J Respir Crit Care Med. 2020;201(11):1430–34. DOI: 10.1164/rccm.202003-0736LE
Fibrinolytic therapy to treat ARDS in the setting of COVID-19 infection [Internet]. [cited 2024 Aug 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT04357730
Tenecteplase in patients with COVID-19 [Internet]. [cited 2024 Aug 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT04505592
Low-Dose tenecteplase in COVID-19 diagnosed with pulmonary embolism [Internet]. [cited 2024 Aug 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT04558125
Iba T, Levy JH, Thachil J, Wada H, Levi M; Scientific and Standardization Committee on DIC of the International Society on Thrombosis and Haemostasis. The progression from coagulopathy to disseminated intravascular coagulation in representative underlying diseases. Thromb Res. 2019;179:11–14. DOI: 10.1016/j.thromres.2019.04.030
Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417–18. DOI: 10.1016/S0140-6736(20)30937-5
Wang J, Hajizadeh N, Moore EE, McIntyre RC, Moore PK, Veress LA, et al. Tissue plasminogen activator (tPA) treatment for COVID-19 associated acute respiratory distress syndrome (ARDS): A case series. J Thromb Haemost. 2020;18(7):1752–55.
Barrett CD, Oren-Grinberg A, Chao E, Moraco AH, Martin MJ, Reddy SH, et al. Rescue therapy for severe COVID-19-associated acute respiratory distress syndrome with tissue plasminogen activator: A case series. J Trauma Acute Care Surg. 2020;89(3):453–57. DOI: 10.1097/TA.0000000000002786
Moore HB, Barrett CD, Moore EE, Jhunjhunwala R, McIntyre RC, Moore PK, et al. Study of alteplase for respiratory failure in severe acute respiratory syndrome coronavirus 2/COVID-19: Study design of the phase IIa STARS trial. Res Pract Thromb Haemost. 2020;4(6):984–96. DOI: 10.1002/rth2.12395
Poor HD, Ventetuolo CE, Tolbert T, Chun G, Serrao G, Zeidman A, et al. COVID-19 critical illness pathophysiology driven by diffuse pulmonary thrombi and pulmonary endothelial dysfunction responsive to thrombolysis. Clin Transl Med. 2020;10(2). DOI: 10.1002/ctm2.44
Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020;135(23):2033–40. DOI: 10.1182/blood.2020006000
Ruscitti P, Giacomelli R. Ferritin and severe COVID-19, from clinical observations to pathogenic implications and therapeutic perspectives. Isr Med Assoc J. 2020;22(8):516–18.
McGonagle D, Sharif K, O'Regan A, Bridgewood C. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev. 2020;19(6):102537. DOI: 10.1016/j.autrev.2020.102537
Nehring SM, Goyal A, Patel BC. C reactive protein [Internet]. Treasure Island: StatPearls Publishing; 2024 Jan [cited 2024 Aug 5]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441843/
Bounds EJ, Kok SJ. D Dimer [Internet]. Treasure Island: StatPearls Publishing; 2024 Jan [cited 2024 Aug 5]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431064/
Song J, Park DW, Moon S, Cho HJ, Park JH, Seok H, et al. Diagnostic and prognostic value of interleukin-6, pentraxin 3, and procalcitonin levels among sepsis and septic shock patients: A prospective controlled study according to the Sepsis-3 definitions. BMC Infect Dis. 2019;19:968. DOI: 10.1186/s12879-019-4618-7
Nawrot O. The biogenetical revolution of the Council of Europe – twenty years of the Convention on Human Rights and Biomedicine (Oviedo Convention). Life Sci Soc Policy. 2018;14:11. DOI: 10.1186/s40504-018-0073-2
Ministry of Health of Ukraine. On the Approval of the Procedure for Conducting Clinical Trials of Medicinal Products and Examination of Clinical Trial Materials, and the Model Regulation on Ethics Committees [Internet]. 2009 [cited 2024 Aug 5]. Order No. 690, 2009 Sep 23. Available from: https://zakon.rada.gov.ua/laws/show/z0743-09#Text
Guillon A, Laurent E, Godillon L, Kimmoun A, Grammatico-Guillon L. In-hospital mortality rates of critically ill COVID-19 patients in France: A nationwide cross-sectional study of 45,409 ICU patients. Br J Anaesth. 2021;127(5):180–82. DOI: 10.1016/j.bja.2021.08.006
Malas MB, Naazie IN, Elsayed N, Mathlouthi A, Marmor R, Clary B. Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: A systematic review and meta-analysis. EClinicalMedicine. 2020;29:100639. DOI: 10.1016/j.eclinm.2020.100639
Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844–47.
Iba T, Levy JH, Levi M, Thachil J. Coagulopathy in COVID-19. J Thromb Haemost. 2020;18(9):2103–9. DOI: 10.1111/jth.14975
Asakura H, Ogawa H. COVID-19-associated coagulopathy and disseminated intravascular coagulation. Int J Hematol. 2021;113(1):45–57. DOI: 10.1007/s12185-020-03029-y
Mestre-Gómez B, Lorente-Ramos RM, Rogado J, Franco-Moreno A, Obispo B, Salazar-Chiriboga D, et al. Thrombosis and thrombolysis in COVID-19: A study by the Infanta Leonor Thrombosis Research Group. J Thromb Thrombolysis. 2021;51:40–46. DOI: 10.1007/s11239-020-02190-9
Liao SC, Shao SC, Chen YT, Chen YC, Hung MJ. Incidence and mortality of pulmonary embolism in COVID-19: A systematic review and meta-analysis. Crit Care. 2020;24(1):464. DOI: 10.1186/s13054-020-03175-z
De Cobelli F, Palumbo D, Ciceri F, Landoni G, Ruggeri A, Rovere-Querini P, et al. Pulmonary vascular thrombosis in COVID-19 pneumonia. J Cardiothorac Vasc Anesth. 2021;35(12):3631–41. DOI: 10.1053/j.jvca.2021.01.011
Woodard PK. Pulmonary thromboembolism in COVID-19. Radiology. 2020;298(2):E107–8. DOI: 10.1148/radiol.2020204175
Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, et al. 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(4):543–3. DOI: 10.1093/eurheartj/ehz405
Dudzinski DM, Giri J, Rosenfield K. Interventional treatment of pulmonary embolism. Circ Cardiovasc Interv. 2017;10(2):e004345. DOI: 10.1161/CIRCINTERVENTIONS.116.004345
Akdis D, Chen K, Saguner AM, Stämpfli SF, Chen X, Chen L, et al. Clinical characteristics of patients with a right ventricular thrombus in arrhythmogenic right ventricular cardiomyopathy. Thromb Haemost. 2019;119(8):1373–78. DOI: 10.1055/s-0039-1688829
Sakr Y, Giovini M, Leone M, Pizzilli G, Kortgen A, Bauer M, et al. Pulmonary embolism in patients with coronavirus disease-2019 (COVID-19) pneumonia: A narrative review. Ann Intensive Care. 2020;10:124. DOI: 10.1186/s13613-020-00741-0
Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, et al. High risk of thrombosis in patients with severe SARS-Cov-2 infection: A multicenter prospective cohort study. Intensive Care Med. 2020;46(6):1089–98. DOI: 10.1007/s00134-020-06062-x
Martínez Chamorro E, Revilla Ostolaza TY, Pérez Núñez M, Borruel Nacenta S, Cruz-Conde Rodríguez-Guerra C, Ibáñez Sanz L. Pulmonary embolisms in patients with COVID-19: A prevalence study in a tertiary hospital. Radiología (English Edition). 2021;63(1):13–21. DOI: 10.1016/j.rxeng.2020.09.011
Poissy J, Goutay J, Caplan M, Parmentier E, Duburcq T, Lassalle F, Jeanpierre E, et al. Pulmonary embolism in patients with COVID-19: Awareness of an increased prevalence. Circulation. 2020;142(2):184–86. DOI: 10.1161/CIRCULATIONAHA.120.047430
Kapała P, Versace M, Tuchendler E, Marciniak A, Guzik P. Pulmonary embolism in patients with the Coronavirus Disease 2019. J Med Sci. 2022;91(1):e602. DOI: 10.20883/e602
Suh YJ, Hong H, Ohana M, Bompard F, Revel MP, Valle C, et al. Pulmonary embolism and deep vein thrombosis in COVID-19: A systematic review and meta-analysis. Radiology. 2021;298(2):E70–E80. DOI: 10.1148/radiol.2020203557
Miesbach W, Makris M. COVID-19: Coagulopathy, risk of thrombosis, and the rationale for anticoagulation. Clin Appl Thromb Hemost. 2020;26:1076029620938149. DOI: 10.1177/1076029620938149
Mackman N, Antoniak S, Wolberg AS, Kasthuri R, Key NS. Coagulation abnormalities and thrombosis in patients infected with SARS-CoV-2 and other pandemic viruses. Arterioscler Thromb Vasc Biol. 2020;40(9):2033–44. DOI: 10.1161/ATVBAHA.120.314514
Basman C, Rashid U, Parmar YJ, Kliger C, Kronzon I. The role of percutaneous vacuum-assisted thrombectomy for intracardiac and intravascular pathology. J Card Surg. 2018;33(10):666–72. DOI: 10.1111/jocs.13806
Boehringer Ingelheim Focuses COVID-19 clinical research on alteplase [Internet]. [cited 2024 Aug 5]. Available from: https://www.boehringer-ingelheim.com/press-release/bi-focuses-covid-19-clinical-research-alteplase
Barrios D, Rosa-Salazar V, Morillo R, Nieto R, Fernández S, Zamorano JL, et al. Prognostic significance of right heart thrombi in patients with acute symptomatic pulmonary embolism: Systematic review and meta-analysis. Chest. 2017;151(2):409–16. DOI: 10.1016/j.chest.2016.09.038
Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020;5(7):802–10.
Vlachou M, Drebes A, Candilio L, Weeraman D, Mir N, Murch N, et al. Pulmonary thrombosis in Covid-19: Before, during and after hospital admission. J Thromb Thrombolysis. 2021;51(4):978–84. DOI: 10.1007/s11239-020-02370-7
Anthi A, Konstantonis D, Theodorakopoulou M, Apostolopoulou O, Karampela I, Konstantopoulou G, et al. A Severe COVID-19 case complicated by right atrium thrombus. Am J Case Rep. 2020;21:e926915. DOI: 10.12659/AJCR.926915
Burgos LM, Costabel JP, Galizia Brito V, Sigal A, Maymo D, Iribarren A, Trivi M. Floating right heart thrombi: A pooled analysis of cases reported over the past 10 years. Am J Emerg Med. 2018;36(6):911–15. DOI: 10.1016/j.ajem.2017.10.045
Rai MP, Herzallah K, Alratroot A, Laird-Fick H. The dilemma in the management of haemodynamically stable pulmonary embolism with right heart thrombus. BMJ Case Rep. 2019;12(7):e229162. DOI: 10.1136/bcr-2018-229162
Keeton J, Gonzalez PE, Cox J, Morlend RM, Amin AA, Mammen PPA, et al. Saved by the VAC: Minimally invasive removal of a surely fatal right heart thrombus in a patient with advanced heart failure. Case Rep Cardiol. 2020;2020:7579262. DOI: 10.1155/2020/7579262
Rajput FA, Du L, Woods M, Jacobson K. Percutaneous vacuum-assisted thrombectomy using angiovac aspiration system. Cardiovasc Revasc Med. 2020;21(4):489–93. DOI: 10.1016/j.carrev.2019.12.020
Alharthy A, Faqihi F, Papanikolaou J, Balhamar A, Blaivas M, Memish ZA, Karakitsos D. Thrombolysis in severe COVID-19 pneumonia with massive pulmonary embolism. Am J Emerg Med. 2021;41:261.e1–61.e3. DOI: 10.1016/j.ajem.2020.07.068
Price LC, McCabe C, Garfield B, Wort SJ. Rescue therapy with thrombolysis in patients with severe COVID-19-associated acute respiratory distress syndrome. Pulm Circ. 2020;10(4):2045894020973906. DOI: 10.1177/2045894020973906
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