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Semin Thromb Hemost 2022; 48(01): 019-030
DOI: 10.1055/s-0041-1736166
Review Article

The Impact of SARS-CoV-2 Infection on Blood Coagulation and Fibrinolytic Pathways: A Review of Prothrombotic Changes Caused by COVID-19

Mehran Bahraini
1   Department of Hematology and Blood Transfusion, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
,
Akbar Dorgalaleh
1   Department of Hematology and Blood Transfusion, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
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Abstract

The cardinal pathology of coronavirus disease 2019 (COVID-19) is a primary infection of pulmonary tract cells by severe acute respiratory syndrome coronavirus 2, provoking a local inflammatory response, often accompanied by cytokine storm and acute respiratory distress syndrome, especially in patients with severe disease. Systemic propagation of the disease may associate with thrombotic events, including deep vein thrombosis, pulmonary embolism, and thrombotic microangiopathy, which are important causes of morbidity and mortality in patients with COVID-19. This narrative review describes current knowledge of the pathophysiological mechanisms of COVID-19-associated coagulopathy, with focus on prothrombotic changes in hemostatic mediators, including plasma levels of clotting factors, natural anticoagulants, components of fibrinolytic system, and platelets. It will also highlight the central role of endothelial cells in COVID-19-associated coagulopathy. This narrative review discusses also potential therapeutic strategies for managing thrombotic complications. Awareness by medical experts of contributors to the pathogenesis of thrombotic events in COVID-19 is imperative to develop therapeutics not limited to regular anticoagulants. Instituting cooperation among medical personnel and researchers may lessen this novel virus' impact now, and in the event of recurrence.

Keywords

SARS-CoV-2 - COVID-19 - coagulopathy - thrombosis


Publikationsverlauf

Artikel online veröffentlicht:
25. Oktober 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Sohrabi C, Alsafi Z, O'Neill N. et al. World Health Organization declares global emergency: a review of the 2019 novel coronavirus (COVID-19). Int J Surg 2020; 76: 71-76
    CrossrefPubMedGoogle Scholar
  • 2 Johns Hopkins University.. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Accessed July 27, 2021 at: https://www.arcgis.com/apps/dashboards/bda7594740fd40299423467b48e9ecf6
    PubMedGoogle Scholar
  • 3 Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends 2020; 14 (01) 69-71
    CrossrefPubMedGoogle Scholar
  • 4 Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E. et al; Latin American Network of Coronavirus Disease 2019-COVID-19 Research (LANCOVID-19) Electronic address: https://www.lancovid.org. Clinical, laboratory and imaging features of COVID-19: a systematic review and meta-analysis. Travel Med Infect Dis 2020; 34: 101623
    CrossrefPubMedGoogle Scholar
  • 5 Fernandes Valente Takeda C, Moura de Almeida M, Gonçalves de Aguiar Gomes R. et al. Case report: recurrent clinical symptoms of COVID-19 in healthcare professionals: a series of cases from Brazil. Am J Trop Med Hyg 2020; 103 (05) 1993-1996
    CrossrefPubMedGoogle Scholar
  • 6 Alimohamadi Y, Sepandi M, Taghdir M, Hosamirudsari H. Determine the most common clinical symptoms in COVID-19 patients: a systematic review and meta-analysis. J Prev Med Hyg 2020; 61 (03) E304-E312
    PubMedGoogle Scholar
  • 7 Zhou P, Yang XL, Wang XG. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579 (7798): 270-273
    Google Scholar
  • 8 Hoffmann M, Kleine-Weber H, Schroeder S. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181 (02) 271.e8-280.e8
    CrossrefPubMedGoogle Scholar
  • 9 Tortorici MA, Walls AC, Lang Y. et al. Structural basis for human coronavirus attachment to sialic acid receptors. Nat Struct Mol Biol 2019; 26 (06) 481-489
    CrossrefPubMedGoogle Scholar
  • 10 Kim C-H. SARS-CoV-2 evolutionary adaptation toward host entry and recognition of receptor O-Acetyl sialylation in virus–host interaction. Int J Mol Sci 2020; 21 (12) 4549
    CrossrefPubMedGoogle Scholar
  • 11 Nougier C, Benoit R, Simon M. et al. Hypofibrinolytic state and high thrombin generation may play a major role in SARS-COV2 associated thrombosis. J Thromb Haemost 2020; 18 (09) 2215-2219
    CrossrefPubMedGoogle Scholar
  • 12 Bachler M, Bösch J, Stürzel DP. et al. Impaired fibrinolysis in critically ill COVID-19 patients. Br J Anaesth 2021; 126 (03) 590-598
    CrossrefPubMedGoogle Scholar
  • 13 Zanza C, Racca F, Longhitano Y. et al. Risk management and treatment of coagulation disorders related to COVID-19 infection. Int J Environ Res Public Health 2021; 18 (03) 1268
    CrossrefPubMedGoogle Scholar
  • 14 Mitrovic M, Sabljic N, Cvetkovic Z. et al. Rotational thromboelastometry (ROTEM) profiling of COVID-19 patients. Platelets 2021; 32 (05) 690-696
    CrossrefPubMedGoogle Scholar
  • 15 Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020; 135 (23) 2033-2040
    CrossrefPubMedGoogle Scholar
  • 16 Greinacher A, Selleng K, Mayerle J. et al. Anti-platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein. Blood 2021; 6 (03) 22-29
    PubMedGoogle Scholar
  • 17 Seitz R, Gürtler L, Schramm W. Thromboinflammation in COVID-19: can α2 -macroglobulin help to control the fire?. J Thromb Haemost 2021; 19 (02) 351-354
    CrossrefPubMedGoogle Scholar
  • 18 Lippi G, Sanchis-Gomar F, Favaloro EJ, Lavie CJ, Henry BM. Coronavirus disease 2019–associated coagulopathy. Mayo Clin Proc 2021; 96 (01) 203-217
    CrossrefPubMedGoogle Scholar
  • 19 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497-506
    CrossrefPubMedGoogle Scholar
  • 20 Chen N, Zhou M, Dong X. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395 (10223): 507-513
    CrossrefPubMedGoogle Scholar
  • 21 Wang D, Hu B, Hu C. et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA 2020; 323 (11) 1061-1069
    CrossrefPubMedGoogle Scholar
  • 22 Wu C, Chen X, Cai Y. et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020; 180 (07) 934-943
    CrossrefPubMedGoogle Scholar
  • 23 Guan WJ, Ni ZY, Hu Y. et al; China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382 (18) 1708-1720
    CrossrefPubMedGoogle Scholar
  • 24 Zhou F, Yu T, Du R. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395 (10229): 1054-1062
    CrossrefPubMedGoogle Scholar
  • 25 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 (06) 1421-1424
    CrossrefPubMedGoogle Scholar
  • 26 Ren B, Yan F, Deng Z. et al. Extremely high incidence of lower extremity deep venous thrombosis in 48 patients with severe COVID-19 in Wuhan. Circulation 2020; 142 (02) 181-183
    CrossrefPubMedGoogle Scholar
  • 27 Zhang L, Feng X, Zhang D. et al. Deep vein thrombosis in hospitalized patients with COVID-19 in Wuhan, China: prevalence, risk factors, and outcome. Circulation 2020; 142 (02) 114-128
    CrossrefPubMedGoogle Scholar
  • 28 Middeldorp S, Coppens M, van Haaps TF. et al. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost 2020; 18 (08) 1995-2002
    CrossrefPubMedGoogle Scholar
  • 29 Poissy J, Goutay J, Caplan M. et al; Lille ICU Haemostasis COVID-19 Group. Pulmonary embolism in patients with COVID-19: awareness of an increased prevalence. Circulation 2020; 142 (02) 184-186
    CrossrefPubMedGoogle Scholar
  • 30 Helms J, Tacquard C, Severac F. et al; CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis). High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med 2020; 46 (06) 1089-1098
    CrossrefPubMedGoogle Scholar
  • 31 Wichmann D, Sperhake J-P, Lütgehetmann M. et al. Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study. Ann Intern Med 2020; 173 (04) 268-277
    CrossrefPubMedGoogle Scholar
  • 32 Dolhnikoff M, Duarte-Neto AN, de Almeida Monteiro RA. et al. Pathological evidence of pulmonary thrombotic phenomena in severe COVID-19. J Thromb Haemost 2020; 18 (06) 1517-1519
    CrossrefPubMedGoogle Scholar
  • 33 Carsana L, Sonzogni A, Nasr A. et al. Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study. Lancet Infect Dis 2020; 20 (10) 1135-1140
    CrossrefPubMedGoogle Scholar
  • 34 Menter T, Haslbauer JD, Nienhold R. et al. Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology 2020; 77 (02) 198-209
    CrossrefPubMedGoogle Scholar
  • 35 Ackermann M, Verleden SE, Kuehnel M. et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med 2020; 383 (02) 120-128
    CrossrefPubMedGoogle Scholar
  • 36 Al Raizah A, Al Askar A, Shaheen N. et al. High rate of bleeding and arterial thrombosis in COVID-19: Saudi multicenter study. Thromb J 2021; 19 (01) 13
    CrossrefPubMedGoogle Scholar
  • 37 Ozsu S, Gunay E, Konstantinides SV. A review of venous thromboembolism in COVID-19: a clinical perspective. Clin Respir J 2021; 15 (05) 506-512
    CrossrefPubMedGoogle Scholar
  • 38 Benvenuto D, Giovanetti M, Ciccozzi A, Spoto S, Angeletti S, Ciccozzi M. The 2019-new coronavirus epidemic: evidence for virus evolution. J Med Virol 2020; 92 (04) 455-459
    CrossrefPubMedGoogle Scholar
  • 39 Fox SE, Akmatbekov A, Harbert JL, Li G, Quincy Brown J, Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir Med 2020; 8 (07) 681-686
    CrossrefPubMedGoogle Scholar
  • 40 Connors JM, Levy JH. Thromboinflammation and the hypercoagulability of COVID-19. J Thromb Haemost 2020; 18 (07) 1559-1561
    CrossrefPubMedGoogle Scholar
  • 41 van Langevelde K, Srámek A, Vincken PW, van Rooden J-K, Rosendaal FR, Cannegieter SC. Finding the origin of pulmonary emboli with a total-body magnetic resonance direct thrombus imaging technique. Haematologica 2013; 98 (02) 309-315
    CrossrefPubMedGoogle Scholar
  • 42 Varga Z, Flammer AJ, Steiger P. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020; 395 (10234): 1417-1418
    CrossrefPubMedGoogle Scholar
  • 43 Guo T, Fan Y, Chen M. et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020; 5 (07) 811-818
    CrossrefPubMedGoogle Scholar
  • 44 Barrett CD, Moore HB, Yaffe MB, Moore EE. ISTH interim guidance on recognition and management of coagulopathy in COVID-19: a comment. J Thromb Haemost 2020; 18 (08) 2060-2063
    CrossrefPubMedGoogle Scholar
  • 45 Meziani F, Gando S, Vincent J-L. Should all patients with sepsis receive anticoagulation? Yes. Intensive Care Med 2017; 43: 452-454
    CrossrefPubMedGoogle Scholar
  • 46 Liao JK. Linking endothelial dysfunction with endothelial cell activation. J Clin Invest 2013; 123 (02) 540-541
    CrossrefPubMedGoogle Scholar
  • 47 Finigan JH. The coagulation system and pulmonary endothelial function in acute lung injury. Microvasc Res 2009; 77 (01) 35-38
    CrossrefPubMedGoogle Scholar
  • 48 Sharp C, Millar AB, Medford AR. Advances in understanding of the pathogenesis of acute respiratory distress syndrome. Respiration 2015; 89 (05) 420-434
    CrossrefPubMedGoogle Scholar
  • 49 Han S, Mallampalli RK. The acute respiratory distress syndrome: from mechanism to translation. J Immunol 2015; 194 (03) 855-860
    CrossrefPubMedGoogle Scholar
  • 50 Levi M, van der Poll T, Ten Cate H. Tissue factor in infection and severe inflammation. Semin Thromb Hemost 2006; 32 (01) 33-39
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 51 Sebag SC, Bastarache JA, Ware LB. Therapeutic modulation of coagulation and fibrinolysis in acute lung injury and the acute respiratory distress syndrome. Curr Pharm Biotechnol 2011; 12 (09) 1481-1496
    CrossrefPubMedGoogle Scholar
  • 52 Goshua G, Pine AB, Meizlish ML. et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet Haematol 2020; 7 (08) e575-e582
    CrossrefPubMedGoogle Scholar
  • 53 Meizlish ML, Pine AB, Goshua G. et al. Circulating markers of angiogenesis and endotheliopathy in COVID-19. medRxiv 2020; 15 (03) 45-64
    PubMedGoogle Scholar
  • 54 Favaloro EJ, Henry BM, Lippi G. Increased VWF and decreased ADAMTS-13 in COVID-19: creating a milieu for (micro)thrombosis. Semin Thromb Hemost 2021; 47 (04) 400-418
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 55 Dalan R, Bornstein SR, El-Armouche A. et al. The ACE-2 in COVID-19: foe or friend?. Horm Metab Res 2020; 52 (05) 257-263
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 56 Vaughan DE, Lazos SA, Tong K. Angiotensin II regulates the expression of plasminogen activator inhibitor-1 in cultured endothelial cells. A potential link between the renin-angiotensin system and thrombosis. J Clin Invest 1995; 95 (03) 995-1001
    CrossrefPubMedGoogle Scholar
  • 57 Vaughan DE. Endothelial function, fibrinolysis, and angiotensin-converting enzyme inhibition. Clin Cardiol 1997; 20 (11, Suppl 2): II-34-II-37
    CrossrefPubMedGoogle Scholar
  • 58 Nakamura S, Nakamura I, Ma L, Vaughan DE, Fogo AB. Plasminogen activator inhibitor-1 expression is regulated by the angiotensin type 1 receptor in vivo. Kidney Int 2000; 58 (01) 251-259
    CrossrefPubMedGoogle Scholar
  • 59 Mogielnicki A, Kramkowski K, Hermanowicz JM, Leszczynska A, Przyborowski K, Buczko W. Angiotensin-(1-9) enhances stasis-induced venous thrombosis in the rat because of the impairment of fibrinolysis. J Renin Angiotensin Aldosterone Syst 2014; 15 (01) 13-21
    CrossrefPubMedGoogle Scholar
  • 60 Meini S, Zanichelli A, Sbrojavacca R. et al. Understanding the pathophysiology of COVID-19: could the contact system be the key?. Front Immunol 2020; 11: 2014
    CrossrefPubMedGoogle Scholar
  • 61 Urwyler P, Moser S, Charitos P. et al. Treatment of COVID-19 with conestat alfa, a regulator of the complement, contact activation and Kallikrein-Kinin system. Front Immunol 2020; 11: 2072
    CrossrefPubMedGoogle Scholar
  • 62 Spence JD, de Freitas GR, Pettigrew LC. et al. Mechanisms of stroke in COVID-19. Cerebrovasc Dis 2020; 49 (04) 451-458
    CrossrefPubMedGoogle Scholar
  • 63 Thachil J. Hypoxia–an overlooked trigger for thrombosis in COVID-19 and other critically ill patients. J Thromb Haemost 2020; 18 (11) 3109-3110
    CrossrefPubMedGoogle Scholar
  • 64 Pilli VS, Datta A, Afreen S, Catalano D, Szabo G, Majumder R. Hypoxia downregulates protein S expression. Blood 2018; 132 (04) 452-455
    CrossrefPubMedGoogle Scholar
  • 65 Prchal JT. Hypoxia and thrombosis. Blood 2018; 132 (04) 348-349
    CrossrefPubMedGoogle Scholar
  • 66 Wang GL, Jiang B-H, Rue EA, Semenza GL. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A 1995; 92 (12) 5510-5514
    CrossrefPubMedGoogle Scholar
  • 67 Görlach A, Diebold I, Schini-Kerth VB. et al. Thrombin activates the hypoxia-inducible factor-1 signaling pathway in vascular smooth muscle cells: role of the p22(phox)-containing NADPH oxidase. Circ Res 2001; 89 (01) 47-54
    CrossrefPubMedGoogle Scholar
  • 68 Gupta N, Zhao Y-Y, Evans CE. The stimulation of thrombosis by hypoxia. Thromb Res 2019; 181: 77-83
    CrossrefPubMedGoogle Scholar
  • 69 Ogawa S, Gerlach H, Esposito C, Pasagian-Macaulay A, Brett J, Stern D. Hypoxia modulates the barrier and coagulant function of cultured bovine endothelium. Increased monolayer permeability and induction of procoagulant properties. J Clin Invest 1990; 85 (04) 1090-1098
    CrossrefPubMedGoogle Scholar
  • 70 Ogawa S, Shreeniwas R, Brett J, Clauss M, Furie M, Stern DM. The effect of hypoxia on capillary endothelial cell function: modulation of barrier and coagulant function. Br J Haematol 1990; 75 (04) 517-524
    CrossrefPubMedGoogle Scholar
  • 71 Ogawa S, Shreeniwas R, Butura C, Brett J, Stern DM. Modulation of endothelial function by hypoxia: perturbation of barrier and anticoagulant function, and induction of a novel factor X activator. Adv Exp Med Biol 1990; 281: 303-312
    CrossrefPubMedGoogle Scholar
  • 72 Rivara S, Milazzo FM, Giannini G. Heparanase: a rainbow pharmacological target associated to multiple pathologies including rare diseases. Future Med Chem 2016; 8 (06) 647-680
    CrossrefPubMedGoogle Scholar
  • 73 Faber DR, de Groot PG, Visseren FL. Role of adipose tissue in haemostasis, coagulation and fibrinolysis. Obes Rev 2009; 10 (05) 554-563
    CrossrefPubMedGoogle Scholar
  • 74 Sattar N, McInnes IB, McMurray JJV. Obesity is a risk factor for severe COVID-19 infection: multiple potential mechanisms. Circulation 2020; 142 (01) 4-6
    CrossrefPubMedGoogle Scholar
  • 75 Vilahur G, Ben-Aicha S, Badimon L. New insights into the role of adipose tissue in thrombosis. Cardiovasc Res 2017; 113 (09) 1046-1054
    CrossrefPubMedGoogle Scholar
  • 76 Beyrouti R, Adams ME, Benjamin L. et al. Characteristics of ischaemic stroke associated with COVID-19. J Neurol Neurosurg Psychiatry 2020; 91 (08) 889-891
    CrossrefPubMedGoogle Scholar
  • 77 Harzallah I, Debliquis A, Drénou B. Lupus anticoagulant is frequent in patients with Covid-19: response to reply. J Thromb Haemost 2020; 12 (04) 34-50
    PubMedGoogle Scholar
  • 78 Oxley TJ, Mocco J, Majidi S. et al. Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med 2020; 382 (20) e60
    CrossrefPubMedGoogle Scholar
  • 79 Favaloro EJ, Henry BM, Lippi G. COVID-19 and antiphospholipid antibodies: time for a reality check?. Semin Thromb Hemost; 2021. (e-pub ahead of print) DOI: 10.1055/s-0041-1728832
    Artikel in Thieme ConnectGoogle Scholar
  • 80 Favaloro EJ, Henry BM, Lippi G. Is lupus anticoagulant a significant feature of COVID-19? A critical appraisal of the literature. Semin Thromb Hemost; 2021. (e-pub ahead of print) DOI: 10.1055/s-0041-1729856
    Artikel in Thieme ConnectGoogle Scholar
  • 81 Vannini L, Llanos Gómez JM, Quijada-Fumero A, Fernández Pérez AB, Hernández Afonso JS. COVID-19 quarantine and acute pulmonary embolism. Rev Esp Cardiol (Engl Ed) 2020; 73 (08) 680-682
    CrossrefPubMedGoogle Scholar
  • 82 Ali A, Omore I, Asare L, Gabani M, Riaz M. Seated-immobility thromboembolism syndrome complicating coronavirus disease 2019 outbreak quarantine. Chest 2020; 158 (04) A1614
    CrossrefPubMedGoogle Scholar
  • 83 Panigada M, Bottino N, Tagliabue P. et al. Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis. J Thromb Haemost 2020; 18 (07) 1738-1742
    CrossrefPubMedGoogle Scholar
  • 84 Tabatabai A, Rabin J, Menaker J. et al. Factor VIII and functional protein C activity in critically ill patients with coronavirus disease 2019: a case series. A A Pract 2020; 14 (07) e01236
    CrossrefPubMedGoogle Scholar
  • 85 Cipolloni L, Sessa F, Bertozzi G. et al. Preliminary post-mortem COVID-19 evidence of endothelial injury and factor VIII hyperexpression. Diagnostics (Basel) 2020; 10 (08) 575
    CrossrefPubMedGoogle Scholar
  • 86 von Meijenfeldt FA, Havervall S, Adelmeijer J. et al. Prothrombotic changes in patients with COVID-19 are associated with disease severity and mortality. Res Pract Thromb Haemost 2020; 5 (01) 132-141
    CrossrefPubMedGoogle Scholar
  • 87 Shovlin CL, Angus G, Manning RA. et al. Endothelial cell processing and alternatively spliced transcripts of factor VIII: potential implications for coagulation cascades and pulmonary hypertension. PLoS One 2010; 5 (02) e9154
    CrossrefPubMedGoogle Scholar
  • 88 Jacquemin M, Neyrinck A, Hermanns MI. et al. FVIII production by human lung microvascular endothelial cells. Blood 2006; 108 (02) 515-517
    CrossrefPubMedGoogle Scholar
  • 89 Huisman A, Beun R, Sikma M, Westerink J, Kusadasi N. Involvement of ADAMTS13 and von Willebrand factor in thromboembolic events in patients infected with SARS-CoV-2. Int J Lab Hematol 2020; 42 (05) e211-e212
    CrossrefPubMedGoogle Scholar
  • 90 von Meijenfeldt FA, Havervall S, Adelmeijer J. et al. Sustained prothrombotic changes in COVID-19 patients 4 months after hospital discharge. Blood Adv 2021; 5 (03) 756-759
    CrossrefPubMedGoogle Scholar
  • 91 Zhang Y, Cao W, Jiang W. et al. Profile of natural anticoagulant, coagulant factor and anti-phospholipid antibody in critically ill COVID-19 patients. J Thromb Thrombolysis 2020; 50 (03) 580-586
    CrossrefPubMedGoogle Scholar
  • 92 Stefely JA, Christensen BB, Gogakos T. et al. Marked factor V activity elevation in severe COVID-19 is associated with venous thromboembolism. Am J Hematol 2020; 95 (12) 1522-1530
    CrossrefPubMedGoogle Scholar
  • 93 Hess R, Wujak L, Hesse C. et al. Coagulation factor XII regulates inflammatory responses in human lungs. Thromb Haemost 2017; 117 (10) 1896-1907
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 94 Stoichitoiu LE, Pinte L, Balea MI, Nedelcu V, Badea C, Baicus C. Anticoagulant protein S in COVID-19: low activity, and associated with outcome. Rom J Intern Med 2020; 58 (04) 251-258
    PubMedGoogle Scholar
  • 95 van de Poel RH, Meijers JC, Bouma BN. Interaction between protein S and complement C4b-binding protein (C4BP). Affinity studies using chimeras containing c4bp β-chain short consensus repeats. J Biol Chem 1999; 274 (21) 15144-15150
    CrossrefPubMedGoogle Scholar
  • 96 Khan R, Yasmeen A, Pandey AK, Al Saffar K, Narayanan SR. Cerebral venous thrombosis and acute pulmonary embolism following varicella infection. Eur J Case Rep Intern Med 2019; 6 (10) 001171
    PubMedGoogle Scholar
  • 97 Vila N, Reverter JC, Yagüe J, Chamorro A. Interaction between interleukin-6 and the natural anticoagulant system in acute stroke. J Interferon Cytokine Res 2000; 20 (03) 325-329
    CrossrefPubMedGoogle Scholar
  • 98 Conti P, Ronconi G, Caraffa A. et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents 2020; 34 (02) 327-331
    PubMedGoogle Scholar
  • 99 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 (06) 102537
    CrossrefPubMedGoogle Scholar
  • 100 Chen X, Zhao B, Qu Y. et al. Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients. Clin Infect Dis 2020; 45 (05) 155-163
    PubMedGoogle Scholar
  • 101 Ulhaq ZS, Soraya GV. Interleukin-6 as a potential biomarker of COVID-19 progression. Med Mal Infect 2020; 50 (04) 382-383
    CrossrefPubMedGoogle Scholar
  • 102 Chatterjee S, Sengupta T, Majumder S, Majumder R. COVID-19: a probable role of the anticoagulant Protein S in managing COVID-19-associated coagulopathy. Aging (Albany NY) 2020; 12 (16) 15954-15961
    CrossrefPubMedGoogle Scholar
  • 103 Ruzicka JA. Identification of the antithrombotic protein S as a potential target of the SARS-CoV-2 papain-like protease. Thromb Res 2020; 196: 257-259
    CrossrefPubMedGoogle Scholar
  • 104 Lippi G, Henry BM, Sanchis-Gomar F. Plasma antithrombin values are significantly decreased in coronavirus disease 2019 (COVID-19) patients with severe illness. Semin Thromb Hemost 2021; 47 (04) 460-462
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 105 Ranucci M, Ballotta A, Di Dedda U. et al. The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J Thromb Haemost 2020; 18 (07) 1747-1751
    CrossrefPubMedGoogle Scholar
  • 106 Han H, Yang L, Liu R. et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med 2020; 58 (07) 1116-1120
    CrossrefPubMedGoogle Scholar
  • 107 Gazzaruso C, Paolozzi E, Valenti C. et al. Association between antithrombin and mortality in patients with COVID-19. A possible link with obesity. Nutr Metab Cardiovasc Dis 2020; 30 (11) 1914-1919
    CrossrefPubMedGoogle Scholar
  • 108 Anaklı İ, Ergin Özcan P, Polat Ö. et al. Prognostic value of antithrombin levels in COVID-19 patients and impact of fresh frozen plasma treatment: a retrospective study. Turk J Haematol 2021; 38 (01) 15-21
    PubMedGoogle Scholar
  • 109 Liao D, Zhou F, Luo L. et al. Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study. Lancet Haematol 2020; 7 (09) e671-e678
    CrossrefPubMedGoogle Scholar
  • 110 Gross O, Moerer O, Weber M, Huber TB, Scheithauer S. COVID-19-associated nephritis: early warning for disease severity and complications?. Lancet 2020; 395 (10236): e87-e88
    CrossrefPubMedGoogle Scholar
  • 111 Boscolo A, Spiezia L, Correale C. et al. Different hypercoagulable profiles in patients with COVID-19 admitted to the internal medicine ward and the intensive care unit. Thromb Haemost 2020; 120 (10) 1474-1477
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 112 Levy JH, Sniecinski RM, Welsby IJ, Levi M. Antithrombin: anti-inflammatory properties and clinical applications. Thromb Haemost 2016; 115 (04) 712-728
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 113 Terpos E, Ntanasis-Stathopoulos I, Elalamy I. et al. Hematological findings and complications of COVID-19. Am J Hematol 2020; 95 (07) 834-847
    CrossrefPubMedGoogle Scholar
  • 114 Bharadwaj J, Jayaraman C, Shrivastava R. Heparin resistance. Lab Hematol 2003; 9 (03) 125-131
    PubMedGoogle Scholar
  • 115 Arachchillage DJ, Remmington C, Rosenberg A. et al. Anticoagulation with argatroban in patients with acute antithrombin deficiency in severe COVID-19. Br J Haematol 2020; 190 (05) e286-e288
    CrossrefPubMedGoogle Scholar
  • 116 Salem N, Atallah B, El Nekidy WS, Sadik ZG, Park WM, Mallat J. Thromboelastography findings in critically ill COVID-19 patients. J Thromb Thrombolysis 2021; 51 (04) 961-965
    CrossrefPubMedGoogle Scholar
  • 117 Wright FL, Vogler TO, Moore EE. et al. Fibrinolysis shutdown correlation with thromboembolic events in severe COVID-19 infection. J Am Coll Surg 2020; 231 (02) 193.e1-203.e1
    CrossrefPubMedGoogle Scholar
  • 118 Creel-Bulos C, Auld SC, Caridi-Scheible M. et al. Fibrinolysis shutdown and thrombosis in a COVID-19 ICU. Shock 2021; 55 (03) 316-320
    CrossrefPubMedGoogle Scholar
  • 119 Ibañez C, Perdomo J, Calvo A. et al. High D dimers and low global fibrinolysis coexist in COVID19 patients: what is going on in there?. J Thromb Thrombolysis 2021; 51 (02) 308-312
    CrossrefPubMedGoogle Scholar
  • 120 Collett LW, Gluck S, Strickland RM, Reddi BJ. Evaluation of coagulation status using viscoelastic testing in intensive care patients with coronavirus disease 2019 (COVID-19): an observational point prevalence cohort study. Aust Crit Care 2021; 34 (02) 155-159
    CrossrefPubMedGoogle Scholar
  • 121 Weiss E, Roux O, Moyer J-D. et al. Fibrinolysis resistance: a potential mechanism underlying COVID-19 coagulopathy. Thromb Haemost 2020; 120 (09) 1343-1345
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 122 Tsantes AE, Frantzeskaki F, Tsantes AG. et al. The haemostatic profile in critically ill COVID-19 patients receiving therapeutic anticoagulant therapy: an observational study. Medicine (Baltimore) 2020; 99 (47) e23365
    CrossrefPubMedGoogle Scholar
  • 123 Blasi A, von Meijenfeldt FA, Adelmeijer J. et al. In vitro hypercoagulability and ongoing in vivo activation of coagulation and fibrinolysis in COVID-19 patients on anticoagulation. J Thromb Haemost 2020; 18 (10) 2646-2653
    CrossrefPubMedGoogle Scholar
  • 124 Kwaan HC, Lindholm PF. The central role of fibrinolytic response in COVID-19—a hematologist's perspective. Int J Mol Sci 2021; 22 (03) 1283
    CrossrefPubMedGoogle Scholar
  • 125 Grau GE, de Moerloose P, Bulla O. et al. Haemostatic properties of human pulmonary and cerebral microvascular endothelial cells. Thromb Haemost 1997; 77 (03) 585-590
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 126 MacLaren R, Stringer KA. Emerging role of anticoagulants and fibrinolytics in the treatment of acute respiratory distress syndrome. Pharmacotherapy 2007; 27 (06) 860-873
    CrossrefPubMedGoogle Scholar
  • 127 Whyte CS, Morrow GB, Mitchell JL, Chowdary P, Mutch NJ. Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19. J Thromb Haemost 2020; 18 (07) 1548-1555
    CrossrefPubMedGoogle Scholar
  • 128 Fujimoto H, Gabazza EC, Hataji O. et al. Thrombin-activatable fibrinolysis inhibitor and protein C inhibitor in interstitial lung disease. Am J Respir Crit Care Med 2003; 167 (12) 1687-1694
    CrossrefPubMedGoogle Scholar
  • 129 Sun W, Li ZR, Shi ZC, Zhang NF, Zhang YC. Changes in coagulation and fibrinolysis of post-SARS osteonecrosis in a Chinese population. Int Orthop 2006; 30 (03) 143-146
    CrossrefPubMedGoogle Scholar
  • 130 Wiwanitkit V. ed. Thrombohemostatic disorder in new viral emerging diseases. In: Thrombohemostatic Disease Research. New York, NY: Nova Science Publishers; 2006: 181-186
    Google Scholar
  • 131 Hardy M, Michaux I, Lessire S. et al. Prothrombotic disturbances of hemostasis of patients with severe COVID-19: a prospective longitudinal observational study. Thromb Res 2021; 197: 20-23
    CrossrefPubMedGoogle Scholar
  • 132 Masi P, Hékimian G, Lejeune M. et al. Systemic inflammatory response syndrome is a major contributor to COVID-19-associated coagulopathy: insights from a prospective, single-center cohort study. Circulation 2020; 142 (06) 611-614
    CrossrefPubMedGoogle Scholar
  • 133 Yang M, Ng MH, Li CK. Thrombocytopenia in patients with severe acute respiratory syndrome (review). Hematology 2005; 10 (02) 101-105
    CrossrefPubMedGoogle Scholar
  • 134 Peiris JSM, Chu C-M, Cheng VC-C. et al; HKU/UCH SARS Study Group. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet 2003; 361 (9371): 1767-1772
    CrossrefPubMedGoogle Scholar
  • 135 Lee N, Hui D, Wu A. et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med 2003; 348 (20) 1986-1994
    CrossrefPubMedGoogle Scholar
  • 136 Zou Z, Yang Y, Chen J. et al. Prognostic factors for severe acute respiratory syndrome: a clinical analysis of 165 cases. Clin Infect Dis 2004; 38 (04) 483-489
    CrossrefPubMedGoogle Scholar
  • 137 Tsang KW, Ho PL, Ooi GC. et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med 2003; 348 (20) 1977-1985
    CrossrefPubMedGoogle Scholar
  • 138 Liu C-L, Lu Y-T, Peng M-J. et al. Clinical and laboratory features of severe acute respiratory syndrome vis-a-vis onset of fever. Chest 2004; 126 (02) 509-517
    CrossrefPubMedGoogle Scholar
  • 139 Wang J-T, Sheng W-H, Fang C-T. et al. Clinical manifestations, laboratory findings, and treatment outcomes of SARS patients. Emerg Infect Dis 2004; 10 (05) 818-824
    CrossrefPubMedGoogle Scholar
  • 140 Lang ZW, Zhang LJ, Zhang SJ. et al. A clinicopathological study of three cases of severe acute respiratory syndrome (SARS). Pathology 2003; 35 (06) 526-531
    CrossrefPubMedGoogle Scholar
  • 141 Min C-K, Cheon S, Ha N-Y. et al. Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity. Sci Rep 2016; 6 (01) 25359
    CrossrefPubMedGoogle Scholar
  • 142 Ko J-H, Park GE, Lee JY. et al. Predictive factors for pneumonia development and progression to respiratory failure in MERS-CoV infected patients. J Infect 2016; 73 (05) 468-475
    CrossrefPubMedGoogle Scholar
  • 143 Memish ZA, Zumla AI, Al-Hakeem RF, Al-Rabeeah AA, Stephens GM. Family cluster of Middle East respiratory syndrome coronavirus infections. N Engl J Med 2013; 368 (26) 2487-2494
    CrossrefPubMedGoogle Scholar
  • 144 Assiri A, McGeer A, Perl TM. et al; KSA MERS-CoV Investigation Team. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med 2013; 369 (05) 407-416
    CrossrefPubMedGoogle Scholar
  • 145 Al-Tawfiq JA, Hinedi K, Abbasi S, Babiker M, Sunji A, Eltigani M. Hematologic, hepatic, and renal function changes in hospitalized patients with Middle East respiratory syndrome coronavirus. Int J Lab Hematol 2017; 39 (03) 272-278
    CrossrefPubMedGoogle Scholar
  • 146 Liu Y, Sun W, Guo Y. et al. Association between platelet parameters and mortality in coronavirus disease 2019: retrospective cohort study. Platelets 2020; 31 (04) 490-496
    CrossrefPubMedGoogle Scholar
  • 147 Zhang Y, Zeng X, Jiao Y. et al. Mechanisms involved in the development of thrombocytopenia in patients with COVID-19. Thromb Res 2020; 193: 110-115
    CrossrefPubMedGoogle Scholar
  • 148 Yang X, Yang Q, Wang Y. et al. Thrombocytopenia and its association with mortality in patients with COVID-19. J Thromb Haemost 2020; 18 (06) 1469-1472
    CrossrefPubMedGoogle Scholar
  • 149 Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta 2020; 506: 145-148
    CrossrefPubMedGoogle Scholar
  • 150 Jiang SQ, Huang QF, Xie WM, Lv C, Quan XQ. The association between severe COVID-19 and low platelet count: evidence from 31 observational studies involving 7613 participants. Br J Haematol 2020; 190 (01) e29-e33
    CrossrefPubMedGoogle Scholar
  • 151 Thachil J, Tang N, Gando S. et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost 2020; 18 (05) 1023-1026
    CrossrefPubMedGoogle Scholar
  • 152 Thachil J. What do monitoring platelet counts in COVID-19 teach us?. J Thromb Haemost 2020; 18 (08) 2071-2072
    CrossrefPubMedGoogle Scholar
  • 153 Handtke S, Thiele T. Large and small platelets-(When) do they differ?. J Thromb Haemost 2020; 18 (06) 1256-1267
    CrossrefPubMedGoogle Scholar
  • 154 Amgalan A, Othman M. Exploring possible mechanisms for COVID-19 induced thrombocytopenia: unanswered questions. J Thromb Haemost 2020; 18 (06) 1514-1516
    CrossrefPubMedGoogle Scholar
  • 155 Manne BK, Denorme F, Middleton EA. et al. Platelet gene expression and function in patients with COVID-19. Blood 2020; 136 (11) 1317-1329
    CrossrefPubMedGoogle Scholar
  • 156 Rapkiewicz AV, Mai X, Carsons SE. et al. Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: a case series. EClinicalMedicine 2020; 24: 100434
    CrossrefPubMedGoogle Scholar
  • 157 Iba T, Levy JH, Levi M, Connors JM, Thachil J. Coagulopathy of coronavirus disease 2019. Crit Care Med 2020; 48 (09) 1358-1364
    CrossrefPubMedGoogle Scholar
  • 158 Salamanna F, Maglio M, Landini MP, Fini M. Platelet functions and activities as potential hematologic parameters related to Coronavirus Disease 2019 (Covid-19). Platelets 2020; 31 (05) 627-632
    CrossrefPubMedGoogle Scholar
  • 159 Zhang S, Liu Y, Wang X. et al. SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19. J Hematol Oncol 2020; 13 (01) 120
    CrossrefPubMedGoogle Scholar
  • 160 Chen Y, Wang J, Liu C. et al. IP-10 and MCP-1 as biomarkers associated with disease severity of COVID-19. Mol Med 2020; 26 (01) 97
    CrossrefPubMedGoogle Scholar
  • 161 Chan AS, Rout A. Use of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in COVID-19. J Clin Med Res 2020; 12 (07) 448-453
    CrossrefPubMedGoogle Scholar
  • 162 Eslamijouybari M, Heydari K, Maleki I. et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in COVID-19 patients and control group and relationship with disease prognosis. Caspian J Intern Med 2020; 11 (Suppl. 01) 531-535
    PubMedGoogle Scholar
  • 163 Zhong Q, Peng J. Mean platelet volume/platelet count ratio predicts severe pneumonia of COVID-19. J Clin Lab Anal 2021; 35 (01) e23607
    CrossrefPubMedGoogle Scholar
  • 164 He J, Wei Y, Chen J, Chen F, Gao W, Lu X. Dynamic trajectory of platelet-related indicators and survival of severe COVID-19 patients. Crit Care 2020; 24 (01) 607
    CrossrefPubMedGoogle Scholar
  • 165 Canzano P, Brambilla M, Porro B. et al. Platelet and endothelial activation as potential mechanisms behind the thrombotic complications of COVID-19 patients. JACC Basic Transl Sci 2021; 6 (03) 202-218
    CrossrefPubMedGoogle Scholar