Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Author(s): Hayder M. Al-Kuraishy, Ali I. Al-Gareeb, Nasser A. Hadi Al-Harcan, Athanasios Alexiou* and Gaber El-Saber Batiha*

DOI: 10.2174/1871530322666220801102402

DownloadDownload PDF Flyer Cite As
Tranexamic Acid and Plasminogen/Plasmin Glaring Paradox in COVID-19

Page: [35 - 45] Pages: 11

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Coronavirus disease 2019 (COVID-19) is caused by a severe acute respiratory syndrome, coronavirus type 2 (SARS-CoV-2), leading to acute tissue injury and an overstated immune response. In COVID-19, there are noteworthy changes in the fibrinolytic system with the development of coagulopathy. Therefore, modulation of the fibrinolytic system may affect the course of COVID-19. Tranexamic acid (TXA) is an anti-fibrinolytic drug that reduces the conversion of plasminogen to plasmin, which is necessary for SARS-CoV-2 infectivity. In addition, TXA has anti-inflammatory, anti-platelet, and anti-thrombotic effects, which may attenuate the COVID-19 severity. Thus, in this narrative review, we try to find the beneficial and harmful effects of TXA in COVID-19.

Keywords: COVID-19, SARS-CoV-2, fibrinolytic system, tranexamic acid, acute lung injury, acute respiratory syndrome, angiotensin converting enzyme 2.

Graphical Abstract

[1]
Al-Kuraishy, H.M.; Al-Gareeb, A.I.; Alzahrani, K.J.; Cruz-Martins, N.; Batiha, G.E. The potential role of neopterin in Covid-19: A new perspective. Mol. Cell. Biochem., 2021, 476(11), 4161-4166.
[http://dx.doi.org/10.1007/s11010-021-04232-z] [PMID: 34319496]
[2]
Al-Kuraishy, H.M.; Al-Gareeb, A.I.; Alzahrani, K.J.; Alexiou, A.; Batiha, G.E. Niclosamide for COVID-19: Bridging the gap. Mol. Biol. Rep., 2021, 48(12), 8195-8202.
[http://dx.doi.org/10.1007/s11033-021-06770-7] [PMID: 34664162]
[3]
Al-Kuraishy, H.M.; Al-Gareeb, A.I.; Alblihed, M.; Cruz-Martins, N.; Batiha, G.E. COVID-19 and risk of acute ischemic stroke and acute lung injury in patients with type ii diabetes mellitus: The anti-inflammatory role of metformin. Front. Med. (Lausanne), 2021, 8, 644295.
[http://dx.doi.org/10.3389/fmed.2021.644295] [PMID: 33718411]
[4]
Al-Kuraishy, H.M.; Al-Gareeb, A.I.; Qusty, N.; Cruz-Martins, N.; El-Saber Batiha, G. Sequential doxycycline and colchicine combination therapy in COVID-19: The salutary effects. Pulm. Pharmacol. Ther., 2021, 67, 102008.
[http://dx.doi.org/10.1016/j.pupt.2021.102008] [PMID: 33727066]
[5]
Al-Kuraishy, H.M.; Al-Gareeb, A.I.; Qusty, N.; Alexiou, A.; Batiha, G.E. Impact of sitagliptin in non-diabetic COVID-19 patients. Curr. Mol. Pharmacol., 2022, 15(4), 683-692.
[PMID: 34477540]
[6]
Al-Kuraishy, H.M.; Hussien, N.R.; Al-Naimi, M.S.; Al-Buhadily, A.K.; Al-Gareeb, A.I.; Lungnier, C. Renin-Angiotensin system and fibrinolytic pathway in COVID-19: One-way skepticism. Biomed. Biotechnol. Res. J., 2020, 4(5), 33.
[7]
McCormack, P.L. Tranexamic acid: A review of its use in the treatment of hyperfibrinolysis. Drugs, 2012, 72(5), 585-617.
[http://dx.doi.org/10.2165/11209070-000000000-00000] [PMID: 22397329]
[8]
Cai, J.; Ribkoff, J.; Olson, S.; Raghunathan, V.; Al-Samkari, H.; DeLoughery, T.G.; Shatzel, J.J. The many roles of tranexamic acid: An overview of the clinical indications for TXA in medical and surgical patients. Eur. J. Haematol., 2020, 104(2), 79-87.
[http://dx.doi.org/10.1111/ejh.13348] [PMID: 31729076]
[9]
Atsev, S.; Tomov, N. Using antifibrinolytics to tackle neuroinflammation. Neural Regen. Res., 2020, 15(12), 2203-2206.
[http://dx.doi.org/10.4103/1673-5374.284979] [PMID: 32594031]
[10]
Lecker, I.; Wang, D.S.; Whissell, P.D.; Avramescu, S.; Mazer, C.D.; Orser, B.A. Tranexamic acid-associated seizures: Causes and treatment. Ann. Neurol., 2016, 79(1), 18-26.
[http://dx.doi.org/10.1002/ana.24558] [PMID: 26580862]
[11]
Watts, G. Utako Okamoto. Lancet, 2016, 387(10035), 2286.
[http://dx.doi.org/10.1016/S0140-6736(16)30697-3] [PMID: 27308678]
[12]
Godier, A.; Roberts, I.; Hunt, B.J. Tranexamic acid: Less bleeding and less thrombosis? Crit. Care, 2012, 16(3), 135.
[http://dx.doi.org/10.1186/cc11374] [PMID: 22748073]
[13]
Nogami, K.; Shima, M.; Matsumoto, T.; Nishiya, K.; Tanaka, I.; Yoshioka, A. Mechanisms of plasmin-catalyzed inactivation of factor VIII: A crucial role for proteolytic cleavage at Arg336 responsible for plasmin-catalyzed factor VIII inactivation. J. Biol. Chem., 2007, 282(8), 5287-5295.
[http://dx.doi.org/10.1074/jbc.M607816200] [PMID: 17189254]
[14]
Li, A.; Wun, T.C. Proteolysis of tissue factor pathway inhibitor (TFPI) by plasmin: effect on TFPI activity. Thromb. Haemost., 1998, 80(3), 423-427.
[http://dx.doi.org/10.1055/s-0037-1615224] [PMID: 9759622]
[15]
Reichel, C.A.; Lerchenberger, M.; Uhl, B.; Rehberg, M.; Berberich, N.; Zahler, S.; Wymann, M.P.; Krombach, F. Plasmin inhibitors prevent leukocyte accumulation and remodeling events in the postischemic microvasculature. PLoS One, 2011, 6(2), e17229.
[http://dx.doi.org/10.1371/journal.pone.0017229] [PMID: 21364954]
[16]
Weber, C.F.; Görlinger, K.; Byhahn, C.; Moritz, A.; Hanke, A.A.; Zacharowski, K.; Meininger, D. Tranexamic acid partially improves platelet function in patients treated with dual anti-platelet therapy. Eur. J. Anaesthesiol., 2011, 28(1), 57-62.
[17]
George, A. Tranexamic acid: An emerging depigmenting agent. Pigment Int., 2016, 3(2), 66.
[http://dx.doi.org/10.4103/2349-5847.196295]
[18]
Zhao, X.; Sun, Y.; Meng, Z.; Yang, Z.; Fan, S.; Ye, T.; Yang, L.; Li, T.; Gu, R.; Wu, Z.; Gan, H.; Dou, G.; Qi, Y.; Liu, S. Preparation and characterization of tranexamic acid modified porous starch and its application as a hemostatic agent. Int. J. Biol. Macromol., 2022, 200, 273-284.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.12.180] [PMID: 35007632]
[19]
Yoshizaki, S.; Kijima, K.; Hara, M.; Saito, T.; Tamaru, T.; Tanaka, M.; Konno, D.J.; Nakashima, Y.; Okada, S. Tranexamic acid reduces heme cytotoxicity via the TLR4/TNF axis and ameliorates functional recovery after spinal cord injury. J. Neuroinflammation, 2019, 16(1), 160.
[http://dx.doi.org/10.1186/s12974-019-1536-y] [PMID: 31358003]
[20]
Levi, M. Disseminated intravascular coagulation. Crit. Care Med., 2007, 35(9), 2191-2195.
[http://dx.doi.org/10.1097/01.CCM.0000281468.94108.4B] [PMID: 17855836]
[21]
Gando, S.; Levi, M.; Toh, C.H. Disseminated intravascular coagulation. Nat. Rev. Dis. Primers, 2016, 2(1), 16037.
[http://dx.doi.org/10.1038/nrdp.2016.37] [PMID: 27250996]
[22]
Boral, B.M.; Williams, D.J.; Boral, L.I. Disseminated intravascular coagulation. Am. J. Clin. Pathol., 2016, 146(6), 670-680.
[http://dx.doi.org/10.1093/ajcp/aqw195] [PMID: 28013226]
[23]
Gatate, Y.; Masaki, N.; Sato, A.; Yasuda, R.; Namba, T.; Yada, H.; Kawamura, A.; Adachi, T. Tranexamic acid controlled chronic disseminated intravascular coagulation associated with aortic dissection and patent false lumen for three years. Intern. Med., 2017, 56(8), 925-929.
[http://dx.doi.org/10.2169/internalmedicine.56.7499] [PMID: 28420841]
[24]
Takahashi, W.; Yoneda, T.; Koba, H.; Ueda, T.; Tsuji, N.; Ogawa, H.; Asakura, H. Potential mechanisms of nafamostat therapy for severe COVID-19 pneumonia with disseminated intravascular coagulation. Int. J. Infect. Dis., 2021, 102, 529-531.
[http://dx.doi.org/10.1016/j.ijid.2020.10.093] [PMID: 33157292]
[25]
Levi, M.; Toh, C.H.; Thachil, J.; Watson, H.G. Guidelines for the diagnosis and management of disseminated intravascular coagulation. Br. J. Haematol., 2009, 145(1), 24-33.
[http://dx.doi.org/10.1111/j.1365-2141.2009.07600.x] [PMID: 19222477]
[26]
Asakura, H. Diversity of disseminated intravascular coagulation and selection of appropriate treatments. Int. J. Hematol., 2021, 113(1), 10-14.
[http://dx.doi.org/10.1007/s12185-020-03030-5] [PMID: 33159644]
[27]
Lillicrap, D. Disseminated intravascular coagulation in patients with 2019-nCoV pneumonia. J. Thromb. Haemost., 2020, 18(4), 786-787.
[http://dx.doi.org/10.1111/jth.14781] [PMID: 32212240]
[28]
Levi, M.; Iba, T. COVID-19 coagulopathy: Is it disseminated intravascular coagulation? Intern. Emerg. Med., 2021, 16(2), 309-312.
[http://dx.doi.org/10.1007/s11739-020-02601-y] [PMID: 33368021]
[29]
Ezihe-Ejiofor, J.A.; Hutchinson, N. Anticlotting mechanisms 1: Physiology and pathology. Contin. Educ. Anaesth. Crit. Care Pain, 2013, 13(3), 87-92.
[http://dx.doi.org/10.1093/bjaceaccp/mks061]
[30]
Zaidi, A.; Green, L. Physiology of haemostasis. Anaesth. Intensive Care Med., 2019, 20(3), 152-158.
[http://dx.doi.org/10.1016/j.mpaic.2019.01.005]
[31]
Brinkman, H.J.M.; Ahnström, J.; Castoldi, E.; Dahlbäck, B.; Marlar, R.A. Pleiotropic anticoagulant functions of protein S, consequences for the clinical laboratory. Communication from the SSC of the ISTH. J. Thromb. Haemost., 2021, 19(1), 281-286.
[http://dx.doi.org/10.1111/jth.15108] [PMID: 33405384]
[32]
Gómez-Mesa, J.E.; Galindo-Coral, S.; Montes, M.C.; Muñoz Martin, A.J. Thrombosis and coagulopathy in COVID-19. Curr. Probl. Cardiol., 2021, 46(3), 100742.
[http://dx.doi.org/10.1016/j.cpcardiol.2020.100742] [PMID: 33243440]
[33]
Al-Kuraishy, H.M.; Al-Gareeb, A.I.; Al-Hussaniy, H.A.; Al-Harcan, N.A.H.; Alexiou, A.; Batiha, G.E. Neutrophil Extracellular Traps (NETs) and COVID-19: A new frontiers for therapeutic modality. Int. Immunopharmacol., 2022, 104, 108516.
[http://dx.doi.org/10.1016/j.intimp.2021.108516] [PMID: 35032828]
[34]
Marietta, M.; Ageno, W.; Artoni, A.; De Candia, E.; Gresele, P.; Marchetti, M.; Marcucci, R.; Tripodi, A. COVID-19 and haemostasis: A position paper from Italian Society on Thrombosis and Haemostasis (SISET). Blood Transfus., 2020, 18(3), 167-169.
[35]
Hussien, N.R.; Al-Niemi, M.S.; Al-Kuraishy, H.M.; Al-Gareeb, A.I. Statins and COVID-19: The neglected front of bidirectional effects. J. Pak. Med. Assoc., 2021, 71(Suppl. 8), S133-S136.
[36]
Levi, M.; Thachil, J.; Iba, T.; Levy, J.H. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol., 2020, 7(6), e438-e440.
[http://dx.doi.org/10.1016/S2352-3026(20)30145-9] [PMID: 32407672]
[37]
Miesbach, W.; Makris, M. COVID-19: Coagulopathy, risk of thrombosis, and the rationale for anticoagulation. Clin. Appl. Thromb. Hemost., 2020, 26, 1076029620938149.
[http://dx.doi.org/10.1177/1076029620938149] [PMID: 32677459]
[38]
Al-Kuraishy, H.M.; Al-Gareeb, A.I.; Faidah, H.; Al-Maiahy, T.J.; Cruz-Martins, N.; Batiha, G.E. The looming effects of estrogen in Covid-19: A rocky rollout. Front. Nutr., 2021, 8, 649128.
[http://dx.doi.org/10.3389/fnut.2021.649128] [PMID: 33816542]
[39]
Lippi, G.; Henry, B.M.; Sanchis-Gomar, F. Plasma anti-thrombin values are significantly decreased in coronavirus disease 2019 (COVID-19) patients with severe illness. Semin. Thromb. Hemost., 2019, 47(4), 460-462.
[40]
Gazzaruso, C.; Paolozzi, E.; Valenti, C.; Brocchetta, M.; Naldani, D.; Grignani, C.; Salvucci, F.; Marino, F.; Coppola, A.; Gallotti, P. Association between antithrombin and mortality in patients with COVID-19. A possible link with obesity. Nutr. Metab. Cardiovasc. Dis., 2020, 30(11), 1914-1919.
[http://dx.doi.org/10.1016/j.numecd.2020.07.040] [PMID: 32907762]
[41]
Mazzeffi, M.; Chow, J.H.; Amoroso, A.; Tanaka, K. Revisiting the protein C pathway: An opportunity for adjunctive intervention in COVID-19? Anesth. Analg., 2020, 131(3), 690-693.
[http://dx.doi.org/10.1213/ANE.0000000000005059] [PMID: 32541255]
[42]
Griffin, J.H.; Lyden, P. COVID-19 hypothesis: Activated protein C for therapy of virus-induced pathologic thromboinflammation. Res. Pract. Thromb. Haemost., 2020, 4(4), 506-509.
[http://dx.doi.org/10.1002/rth2.12362] [PMID: 32548551]
[43]
Kojima, T.; Gando, S.; Morimoto, Y.; Mashio, H.; Goda, Y.; Kawahigashi, H.; Kemmotsu, O. Systematic elucidation of effects of tranexamic acid on fibrinolysis and bleeding during and after cardiopulmonary bypass surgery. Thromb. Res., 2001, 104(5), 301-307.
[http://dx.doi.org/10.1016/S0049-3848(01)00379-6] [PMID: 11738071]
[44]
Kwaan, H.C.; Lindholm, P.F. The central role of fibrinolytic response in COVID-19-a hematologist’s perspective. Int. J. Mol. Sci., 2021, 22(3), 1283.
[http://dx.doi.org/10.3390/ijms22031283] [PMID: 33525440]
[45]
Barrett, C.D.; Moore, H.B.; Moore, E.E.; McIntyre, R.C.; Moore, P.K.; Burke, J.; Hua, F.; Apgar, J.; Talmor, D.S.; Sauaia, A.; Liptzin, D.R.; Veress, L.A.; Yaffe, M.B. Fibrinolytic therapy for refractory COVID-19 acute respiratory distress syndrome: Scientific rationale and review. Res. Pract. Thromb. Haemost., 2020, 4(4), 524-531.
[http://dx.doi.org/10.1002/rth2.12357] [PMID: 32542213]
[46]
Chan, K.H.; Farouji, I.; Slim, J.; Shaaban, H.S.; Guron, G. Tranexamic acid: A potential treatment option for coronavirus disease 2019. J. Glob. Infect. Dis., 2020, 12(3), 160-161.
[http://dx.doi.org/10.4103/jgid.jgid_132_20] [PMID: 33343171]
[47]
Asakura, H.; Ogawa, H. Potential of heparin and nafamostat combination therapy for COVID-19. J. Thromb. Haemost., 2020, 18(6), 1521-1522.
[http://dx.doi.org/10.1111/jth.14858] [PMID: 32302456]
[48]
Barker, A.B.; Wagener, B.M. An ounce of prevention may prevent hospitalization. Physiol. Rev., 2020, 100(3), 1347-1348.
[http://dx.doi.org/10.1152/physrev.00017.2020] [PMID: 32412329]
[49]
Thierry, A.R. Anti-protease treatments targeting plasmin (ogen) and neutrophil elastase may be beneficial in fighting COVID-19. Physiol. Rev., 2020, 100(4), 1597-1598.
[http://dx.doi.org/10.1152/physrev.00019.2020] [PMID: 32639219]
[50]
Parthvi, R.; Mehra, S. Rukma; Mehra, S. Risk of pulmonary embolism due to tranexamic acid: A case study. Am. J. Ther., 2018, 25(4), e512-e514.
[http://dx.doi.org/10.1097/MJT.0000000000000606] [PMID: 28787284]
[51]
Ijaopo, E.O.; Ijaopo, R.O.; Adjei, S. Bilateral pulmonary embolism while receiving tranexamic acid: A case report. J. Med. Case Reports, 2020, 14(1), 1-6.
[52]
Price, L.C.; McCabe, C.; Garfield, B.; Wort, S.J. Thrombosis and COVID-19 pneumonia: The clot thickens! Eur. Respir. J., 2020, 56(1), 2001608.
[http://dx.doi.org/10.1183/13993003.01608-2020] [PMID: 32554532]
[53]
Helms, J.; Clere-Jehl, R.; Bianchini, E.; Le Borgne, P.; Burban, M.; Zobairi, F.; Diehl, J-L.; Grunebaum, L.; Toti, F.; Meziani, F.; Borgel, D. Thrombomodulin favors leukocyte microvesicle fibrinolytic activity, reduces NETosis and prevents septic shock-induced coagulopathy in rats. Ann. Intensive Care, 2017, 7(1), 118.
[PMID: 28050894]
[54]
Coccheri, S. COVID-19: The crucial role of blood coagulation and fibrinolysis. Intern. Emerg. Med., 2020, 15(8), 1369-1373.
[http://dx.doi.org/10.1007/s11739-020-02443-8] [PMID: 32748128]
[55]
Batiha, G.E.; Al-Gareeb, A.I.; Qusti, S.; Alshammari, E.M.; Rotimi, D.; Adeyemi, O.S.; Al-Kuraishy, H.M. Common NLRP3 inflammasome inhibitors and Covid-19: Divide and Conquer. Scientific African, 2021, 18, e01084.
[56]
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), 844-847.
[http://dx.doi.org/10.1111/jth.14768] [PMID: 32073213]
[57]
Cui, S.; Chen, S.; Li, X.; Liu, S.; Wang, F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J. Thromb. Haemost., 2020, 18(6), 1421-1424.
[http://dx.doi.org/10.1111/jth.14830] [PMID: 32271988]
[58]
Wygrecka, M.; Marsh, L.M.; Morty, R.E.; Henneke, I.; Guenther, A.; Lohmeyer, J.; Markart, P.; Preissner, K.T. Enolase-1 promotes plasminogen-mediated recruitment of monocytes to the acutely inflamed lung. Blood, 2009, 113(22), 5588-5598.
[http://dx.doi.org/10.1182/blood-2008-08-170837] [PMID: 19182206]
[59]
Hunt, B.J. The current place of tranexamic acid in the management of bleeding. Anaesthesia, 2015, 70(Suppl. 1), 50-53, e18.
[http://dx.doi.org/10.1111/anae.12910] [PMID: 25440395]
[60]
Baker, S.K.; Strickland, S. A critical role for plasminogen in inflammation. J. Exp. Med., 2020, 217(4), e20191865.
[http://dx.doi.org/10.1084/jem.20191865] [PMID: 32159743]
[61]
Vago, J.P.; Sugimoto, M.A.; Lima, K.M.; Negreiros-Lima, G.L.; Baik, N.; Teixeira, M.M.; Perretti, M.; Parmer, R.J.; Miles, L.A.; Sousa, L.P. Plasminogen and the plasminogen receptor, Plg-RKT, regulate macrophage phenotypic, and functional changes. Front. Immunol., 2019, 10, 1458.
[http://dx.doi.org/10.3389/fimmu.2019.01458] [PMID: 31316511]
[62]
Chen, Y.; Wang, J.; Liu, C.; Su, L.; Zhang, D.; Fan, J.; Yang, Y.; Xiao, M.; Xie, J.; Xu, Y.; Li, Y.; Zhang, S. IP-10 and MCP-1 as biomarkers associated with disease severity of COVID-19. Mol. Med., 2020, 26(1), 97.
[http://dx.doi.org/10.1186/s10020-020-00230-x] [PMID: 33121429]
[63]
Burysek, L.; Syrovets, T.; Simmet, T. The serine protease plasmin triggers expression of MCP-1 and CD40 in human primary monocytes via activation of p38 MAPK and janus kinase (JAK)/STAT signaling pathways. J. Biol. Chem., 2002, 277(36), 33509-33517.
[http://dx.doi.org/10.1074/jbc.M201941200] [PMID: 12093796]
[64]
Wang, Y.; Perlman, S. COVID-19: Inflammatory profile. Annu. Rev. Med., 2021, 73.
[PMID: 34437814]
[65]
Spinella, P.C.; Thomas, K.A.; Turnbull, I.R.; Fuchs, A.; Bochicchio, K.; Schuerer, D.; Reese, S.; Coleoglou Centeno, A.A.; Horn, C.B.; Baty, J.; Shea, S.M.; Meledeo, M.A.; Pusateri, A.E.; Levy, J.H.; Cap, A.P.; Bochicchio, G.V. The Immunologic effect of early intravenous two and four gram bolus dosing of tranexamic acid compared to placebo in patients with severe traumatic bleeding (TAMPITI): A randomized, double-blind, placebo-controlled, single-center trial. Front. Immunol., 2020, 11, 2085.
[http://dx.doi.org/10.3389/fimmu.2020.02085] [PMID: 33013880]
[66]
Jimenez, J.J.; Iribarren, J.L.; Lorente, L.; Rodriguez, J.M.; Hernandez, D.; Nassar, I.; Perez, R.; Brouard, M.; Milena, A.; Martinez, R.; Mora, M.L. Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: A case control study followed by a randomized double-blind controlled trial. Crit. Care, 2007, 11(6), R117.
[http://dx.doi.org/10.1186/cc6173] [PMID: 17988379]
[67]
Teng, Y.; Feng, C.; Liu, Y.; Jin, H.; Gao, Y.; Li, T. Anti-inflammatory effect of tranexamic acid against trauma-hemorrhagic shock-induced acute lung injury in rats. Exp. Anim., 2018, 67(3), 313-320.
[http://dx.doi.org/10.1538/expanim.17-0143] [PMID: 29398669]
[68]
Ryniak, S.; Harbut, P.; Östlund, A.; Mysiak, A.; Jakobsson, J.G. Suspected transfusion related acute lung injury improving following Administration of Tranexamic Acid: A case report. Case Rep. Anesthesiol., 2014, 2014, 710813.
[http://dx.doi.org/10.1155/2014/710813] [PMID: 24995132]
[69]
Medcalf, R.L.; Keragala, C.B.; Myles, P.S. Fibrinolysis and COVID-19: A plasmin paradox. J. Thromb. Haemost., 2020, 18(9), 2118-2122.
[http://dx.doi.org/10.1111/jth.14960] [PMID: 32543119]
[70]
Mariano, R.Z.; Ramos, M.C.; Reis, F. COVID-19 and pulmonary embolism: Do not forget the association! Rev. Soc. Bras. Med. Trop., 2020, 53, e20200234.
[http://dx.doi.org/10.1590/0037-8682-0234-2020] [PMID: 32520085]
[71]
Hofstra, J.J.; Cornet, A.D.; Declerck, P.J.; Dixon, B.; Aslami, H.; Vlaar, A.P.; Roelofs, J.J.; van der Poll, T.; Levi, M.; Schultz, M.J. Nebulized fibrinolytic agents improve pulmonary fibrinolysis but not inflammation in rat models of direct and indirect acute lung injury. PLoS One, 2013, 8(2), e55262.
[http://dx.doi.org/10.1371/journal.pone.0055262] [PMID: 23408962]
[72]
Tucker, T.; Idell, S. Plasminogen-plasmin system in the pathogenesis and treatment of lung and pleural injury. Semin. Thromb. Hemost., 2013, 39(4), 373-381.
[http://dx.doi.org/10.1055/s-0033-1334486] [PMID: 23504608]
[73]
Wu, Y.; Wang, T.; Guo, C.; Zhang, D.; Ge, X.; Huang, Z.; Zhou, X.; Li, Y.; Peng, Q.; Li, J. Plasminogen improves lung lesions and hypoxemia in patients with COVID-19. QJM, 2020, 113(8), 539-545.
[http://dx.doi.org/10.1093/qjmed/hcaa121] [PMID: 32275753]
[74]
Danzi, G.B.; Loffi, M.; Galeazzi, G.; Gherbesi, E. Acute pulmonary embolism and COVID-19 pneumonia: A random association? Eur. Heart J., 2020, 41(19), 1858.
[http://dx.doi.org/10.1093/eurheartj/ehaa254] [PMID: 32227120]
[75]
Liu, C.; Ma, Y.; Su, Z.; Zhao, R.; Zhao, X.; Nie, H.G.; Xu, P.; Zhu, L.; Zhang, M.; Li, X.; Zhang, X.; Matthay, M.A.; Ji, H.L. Meta-analysis of preclinical studies of fibrinolytic therapy for acute lung injury. Front. Immunol., 2018, 9, 1898.
[http://dx.doi.org/10.3389/fimmu.2018.01898] [PMID: 30177934]
[76]
Samson, A.L.; Knaupp, A.S.; Sashindranath, M.; Borg, R.J.; Au, A.E.; Cops, E.J.; Saunders, H.M.; Cody, S.H.; McLean, C.A.; Nowell, C.J.; Hughes, V.A.; Bottomley, S.P.; Medcalf, R.L. Nucleocytoplasmic coagulation: An injury-induced aggregation event that disulfide crosslinks proteins and facilitates their removal by plasmin. Cell Rep., 2012, 2(4), 889-901.
[http://dx.doi.org/10.1016/j.celrep.2012.08.026] [PMID: 23041318]
[77]
Kryvenko, V.; Vadász, I. Molecular mechanisms of Na, K-ATPase dysregulation driving alveolar epithelial barrier failure in severe COVID-19. Am. J. Physiol. Lung Cell. Mol. Physiol., 2021, 320(6), L1186-L11193.
[78]
Wang, J.; Hajizadeh, N.; Moore, E.E.; McIntyre, R.C.; Moore, P.K.; Veress, L.A.; Yaffe, M.B.; Moore, H.B.; Barrett, C.D. Tissue plasminogen activator (tPA) treatment for COVID-19 associated Acute Respiratory Distress Syndrome (ARDS): A case series. J. Thromb. Haemost., 2020, 18(7), 1752-1755.
[http://dx.doi.org/10.1111/jth.14828] [PMID: 32267998]
[79]
Bendjelid, K.; Giraud, R.; Von Düring, S. Treating hypoxemic COVID-19 “ARDS” patients with almitrine: The earlier the better? Anaesth. Crit. Care Pain Med., 2020, 39(4), 451-452.
[http://dx.doi.org/10.1016/j.accpm.2020.07.003] [PMID: 32653550]
[80]
Ji, H.L.; Zhao, R.; Matalon, S.; Matthay, M.A. Elevated plasmin (ogen) as a common risk factor for COVID-19 susceptibility. Physiol. Rev., 2020, 100(3), 1065-1075.
[http://dx.doi.org/10.1152/physrev.00013.2020] [PMID: 32216698]
[81]
Bangalore, S.; Sharma, A.; Slotwiner, A.; Yatskar, L.; Harari, R.; Shah, B.; Ibrahim, H.; Friedman, G.H.; Thompson, C.; Alviar, C.L.; Chadow, H.L.; Fishman, G.; Reynolds, H.R.; Keller, N.; Hochman, J.S. ST-segment elevation in patients with COVID-19 - a case series. N. Engl. J. Med., 2020, 382(25), 2478-2480.
[http://dx.doi.org/10.1056/NEJMc2009020]
[82]
Al-Kuraishy, H.M.; Al-Gareeb, A.I.; Qusti, S.; Alshammari, E.M.; Gyebi, G.A.; Batiha, G.E. Covid-19-induced dysautonomia: A menace of sympathetic storm. ASN Neuro, 2021, 13, 17590914211057635.
[http://dx.doi.org/10.1177/17590914211057635] [PMID: 34755562]
[83]
Varga, Z.; Flammer, A.J.; Steiger, P.; Haberecker, M.; Andermatt, R.; Zinkernagel, A.S.; Mehra, M.R.; Schuepbach, R.A.; Ruschitzka, F.; Moch, H. Endothelial cell infection and endotheliitis in COVID-19. Lancet, 2020, 395(10234), 1417-1418.
[http://dx.doi.org/10.1016/S0140-6736(20)30937-5] [PMID: 32325026]
[84]
Bester, J.; Pretorius, E. Effects of IL-1β IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity. Sci. Rep., 2016, 6(1), 1-10.
[PMID: 28442746]
[85]
Zlamal, J.; Althaus, K.; Jaffal, H.; Häberle, H.; Pelzl, L.; Singh, A.; Witzemann, A.; Weich, K.; Bitzer, M.; Malek, N.; Göpel, S.; Bösmüller, H.; Gawaz, M.; Mirakaj, V.; Rosenberger, P.; Bakchoul, T. Upregulation of cAMP prevents antibody-mediated thrombus formation in COVID-19. Blood Adv., 2022, 6(1), 248-258.
[http://dx.doi.org/10.1182/bloodadvances.2021005210] [PMID: 34753174]
[86]
Asakura, H.; Ogawa, H. COVID-19-associated coagulopathy and disseminated intravascular coagulation. Int. J. Hematol., 2021, 113(1), 45-57.
[http://dx.doi.org/10.1007/s12185-020-03029-y] [PMID: 33161508]
[87]
Upadhyay, S.P.; Mallick, P.N.; Jagia, M.; Singh, R.K. Acute arterial thrombosis associated with inadvertent high dose of tranexamic acid. Indian J. Crit. Care Med., 2013, 17(4), 237-239.
[http://dx.doi.org/10.4103/0972-5229.118443] [PMID: 24133333]
[88]
Savage, R. Thrombosis with tranexamic acid for menorrhagia. Prescriber Update., 2003, 24, 26-27.
[89]
McGonagle, D.; O’Donnell, J.S.; Sharif, K.; Emery, P.; Bridgewood, C. Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. Lancet Rheumatol., 2020, 2(7), e437-e445.
[http://dx.doi.org/10.1016/S2665-9913(20)30121-1] [PMID: 32835247]
[90]
Signoff, J.K.; Fitzgerald, J.C.; Teachey, D.T.; Balamuth, F.; Weiss, S.L. Hypofibrinogenemia is associated with poor outcome and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome in pediatric severe sepsis. Pediatr. Crit. Care Med., 2018, 19(5), 397-405.
[http://dx.doi.org/10.1097/PCC.0000000000001507] [PMID: 29470247]
[91]
Quinton, T.M.; Kim, S.; Derian, C.K.; Jin, J.; Kunapuli, S.P. Plasmin-mediated activation of platelets occurs by cleavage of protease-activated receptor 4. J. Biol. Chem., 2004, 279(18), 18434-18439.
[http://dx.doi.org/10.1074/jbc.M401431200] [PMID: 14973136]
[92]
Amara, U.; Flierl, M.A.; Rittirsch, D.; Klos, A.; Chen, H.; Acker, B.; Brückner, U.B.; Nilsson, B.; Gebhard, F.; Lambris, J.D.; Huber-Lang, M. Molecular intercommunication between the complement and coagulation systems. J. Immunol., 2010, 185(9), 5628-5636.
[http://dx.doi.org/10.4049/jimmunol.0903678] [PMID: 20870944]
[93]
Xie, D.; Xiang, W.; Weng, Y.; Li, J.; Xu, L.; Zhang, X.; Chen, Z. Platelet volume indices for the prognosis of acute ischemic stroke patients with intravenous thrombolysis. Int. J. Neurosci., 2019, 129(4), 344-349.
[http://dx.doi.org/10.1080/00207454.2018.1536054] [PMID: 30311813]
[94]
Subramaniam, S.; Kanse, S.M.; Kothari, H.; Reinhardt, C.; Fletcher, C. Post-transcriptional, post-translational and pharmacological regulation of tissue factor pathway inhibitor. Blood Coagul. Fibrinolysis, 2018, 29(8), 668-682.
[http://dx.doi.org/10.1097/MBC.0000000000000775] [PMID: 30439766]
[95]
Ogawa, H.; Asakura, H. Consideration of tranexamic acid administration to COVID-19 patients. Physiol. Rev., 2020, 100(4), 1595-1596.
[http://dx.doi.org/10.1152/physrev.00023.2020] [PMID: 32639181]