Download PDF
Thromb Haemost 2020; 120(12): 1668-1679
DOI: 10.1055/s-0040-1715841
Review Article

Coagulopathy and Thrombosis as a Result of Severe COVID-19 Infection: A Microvascular Focus

Upendra K. Katneni
1   Department of Pediatrics, The Center for Blood Oxygen Transport and Hemostasis, University of Maryland School of Medicine, Baltimore, Maryland, United States
,
Aikaterini Alexaki
2   Hemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation & Research, U.S. FDA, Silver Spring, Maryland, United States
,
Ryan C. Hunt
2   Hemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation & Research, U.S. FDA, Silver Spring, Maryland, United States
,
Tal Schiller
3   Diabetes, Endocrinology and Metabolic Disease Unit, Kaplan Medical Center, Rehovot, Israel
,
Michael DiCuccio
4   National Center of Biotechnology Information, National Institutes of Health, Bethesda, Maryland, United States
,
Paul W. Buehler
1   Department of Pediatrics, The Center for Blood Oxygen Transport and Hemostasis, University of Maryland School of Medicine, Baltimore, Maryland, United States
,
Juan C. Ibla
5   Division of Cardiac Anesthesia, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, United States
,
Chava Kimchi-Sarfaty
2   Hemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation & Research, U.S. FDA, Silver Spring, Maryland, United States
› Author Affiliations Funding This work was partly supported by funds from the Hemostasis Branch/Division of Plasma Protein Therapeutics/Office of Tissues and Advanced Therapies/Center for Biologics Evaluation and Research of the U.S. Food and Drug Administration. This research was also supported by the Intramural Research Program of the National Library of Medicine at the NIH.
› Further Information
Also available at
   Permissions and Reprints

Abstract

Coronavirus disease of 2019 (COVID-19) is the clinical manifestation of the respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While primarily recognized as a respiratory disease, it is clear that COVID-19 is systemic illness impacting multiple organ systems. One defining clinical feature of COVID-19 has been the high incidence of thrombotic events. The underlying processes and risk factors for the occurrence of thrombotic events in COVID-19 remain inadequately understood. While severe bacterial, viral, or fungal infections are well recognized to activate the coagulation system, COVID-19-associated coagulopathy is likely to have unique mechanistic features. Inflammatory-driven processes are likely primary drivers of coagulopathy in COVID-19, but the exact mechanisms linking inflammation to dysregulated hemostasis and thrombosis are yet to be delineated. Cumulative findings of microvascular thrombosis has raised question if the endothelium and microvasculature should be a point of investigative focus. von Willebrand factor (VWF) and its protease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13), play important role in the maintenance of microvascular hemostasis. In inflammatory conditions, imbalanced VWF-ADAMTS-13 characterized by elevated VWF levels and inhibited and/or reduced activity of ADAMTS-13 has been reported. Also, an imbalance between ADAMTS-13 activity and VWF antigen is associated with organ dysfunction and death in patients with systemic inflammation. A thorough understanding of VWF-ADAMTS-13 interactions during early and advanced phases of COVID-19 could help better define the pathophysiology, guide thromboprophylaxis and treatment, and improve clinical prognosis.

Keywords

COVID-19 - thrombosis - inflammation - ADAMTS-13 - von Willebrand factor


Publication History

Received: 14 May 2020

Accepted: 14 July 2020

Article published online:
24 August 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Lu R, Zhao X, Li J. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395 (10224): 565-574
    CrossrefPubMedSearch in Google Scholar
  • 2 Epidemiology Working Group for NCIP Epidemic Response, Chinese Center for Disease Control and Prevention. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China [in Chinese]. Zhonghua Liu Xing Bing Xue Za Zhi 2020; 41 (02) 145-151
    Search in Google Scholar
  • 3 Singhal T. A review of coronavirus disease-2019 (COVID-19). Indian J Pediatr 2020; 87 (04) 281-286
    CrossrefPubMedSearch in Google Scholar
  • 4 Rothe C, Schunk M, Sothmann P. et al. Transmission of 2019-nCoV infection from an asymptomatic contact in Germany. N Engl J Med 2020; 382 (10) 970-971
    CrossrefPubMedSearch in Google Scholar
  • 5 Petrosillo N, Viceconte G, Ergonul O, Ippolito G, Petersen E. COVID-19, SARS and MERS: are they closely related?. Clin Microbiol Infect 2020; 26 (06) 729-734
    CrossrefPubMedSearch in Google Scholar
  • 6 Gando S, Fujishima S, Saitoh D. Japanese Association for Acute Medicine (JAAM) Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) Study Group. et al; The significance of disseminated intravascular coagulation on multiple organ dysfunction during the early stage of acute respiratory distress syndrome. Thromb Res 2020; 191: 15-21
    CrossrefPubMedSearch in Google Scholar
  • 7 Helms J, Tacquard C, Severac F. CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis). et al; 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
    CrossrefPubMedSearch in Google Scholar
  • 8 Boral BM, Williams DJ, Boral LI. Disseminated intravascular coagulation. Am J Clin Pathol 2016; 146 (06) 670-680
    CrossrefPubMedSearch in Google Scholar
  • 9 Willyard C. Coronavirus blood-clot mystery intensifies. Nature 2020; 581 (7808): 250
    CrossrefPubMedSearch in Google Scholar
  • 10 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
    CrossrefPubMedSearch in Google Scholar
  • 11 Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020; 18 (05) 1094-1099
    CrossrefPubMedSearch in Google Scholar
  • 12 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 (04) 844-847
    CrossrefPubMedSearch in Google Scholar
  • 13 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
    CrossrefPubMedSearch in Google Scholar
  • 14 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
    CrossrefPubMedSearch in Google Scholar
  • 15 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
    CrossrefPubMedSearch in Google Scholar
  • 16 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
    Search in Google Scholar
  • 17 Richardson S, Hirsch JS, Narasimhan M. and the Northwell COVID-19 Research Consortium. et al; Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020; 323 (20) 2052-2059
    CrossrefPubMedSearch in Google Scholar
  • 18 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
    CrossrefPubMedSearch in Google Scholar
  • 19 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
    CrossrefPubMedSearch in Google Scholar
  • 20 Llitjos JF, Leclerc M, Chochois C. et al. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients. J Thromb Haemost 2020; 18 (07) 1743-1746
    CrossrefPubMedSearch in Google Scholar
  • 21 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
    CrossrefPubMedSearch in Google Scholar
  • 22 Klok FA, Kruip MJHA, van der Meer NJM. et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020; 191: 145-147
    CrossrefPubMedSearch in Google Scholar
  • 23 Lodigiani C, Iapichino G, Carenzo L. Humanitas COVID-19 Task Force. et al; Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res 2020; 191: 9-14
    CrossrefPubMedSearch in Google Scholar
  • 24 Middeldorp S, Coppens M, van Haaps TF. et al. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost 2020
    Search in Google Scholar
  • 25 Nahum J, Morichau-Beauchant T, Daviaud F. et al. Venous thrombosis among critically ill patients with coronavirus disease 2019 (COVID-19). JAMA Netw Open 2020; 3 (05) e2010478
    Search in Google Scholar
  • 26 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
    CrossrefPubMedSearch in Google Scholar
  • 27 Zhang C, Zhang Z, Mi J. et al. The cumulative venous thromboembolism incidence and risk factors in intensive care patients receiving the guideline-recommended thromboprophylaxis. Medicine (Baltimore) 2019; 98 (23) e15833
    CrossrefPubMedSearch in Google Scholar
  • 28 Wang J, Hajizadeh N, Moore EE. et al. Tissue plasminogen activator (tPA) treatment for COVID-19 associated acute respiratory distress syndrome (ARDS): a case series. J Thromb Haemost 2020; 18 (07) 1752-1755
    CrossrefPubMedSearch in Google Scholar
  • 29 Zhang L, Yan X, Fan Q. et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost 2020; 18 (06) 1324-1329
    CrossrefPubMedSearch in Google Scholar
  • 30 Urban K, Kirley K, Stevermer JJ. PURLs: it's time to use an age-based approach to D-dimer. J Fam Pract 2014; 63 (03) 155-158
    PubMedSearch in Google Scholar
  • 31 Schäfer M, Werner S. Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol 2008; 9 (08) 628-638
    CrossrefPubMedSearch in Google Scholar
  • 32 Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol 2020; 20 (06) 355-362
    CrossrefPubMedSearch in Google Scholar
  • 33 Hemker HC, Giesen P, Al Dieri R. et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003; 33 (01) 4-15
    CrossrefPubMedSearch in Google Scholar
  • 34 Simpson ML, Goldenberg NA, Jacobson LJ, Bombardier CG, Hathaway WE, Manco-Johnson MJ. Simultaneous thrombin and plasmin generation capacities in normal and abnormal states of coagulation and fibrinolysis in children and adults. Thromb Res 2011; 127 (04) 317-323
    CrossrefPubMedSearch in Google Scholar
  • 35 Wu YP, Wei R, Liu ZH. et al. Analysis of thrombotic factors in severe acute respiratory syndrome (SARS) patients. Thromb Haemost 2006; 96 (01) 100-101
    Thieme ConnectPubMedSearch in Google Scholar
  • 36 Goyal P, Choi JJ, Pinheiro LC. et al. Clinical characteristics of Covid-19 in New York City. N Engl J Med 2020; 382 (24) 2372-2374
    Search in Google Scholar
  • 37 Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020; 46 (05) 846-848
    CrossrefPubMedSearch in Google Scholar
  • 38 Petrie JR, Guzik TJ, Touyz RM. Diabetes, hypertension, and cardiovascular disease: clinical insights and vascular mechanisms. Can J Cardiol 2018; 34 (05) 575-584
    CrossrefPubMedSearch in Google Scholar
  • 39 Milan-Mattos JC, Anibal FF, Perseguini NM. et al. Effects of natural aging and gender on pro-inflammatory markers. Braz J Med Biol Res 2019; 52 (09) e8392
    CrossrefPubMedSearch in Google Scholar
  • 40 Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 2013; 13 (01) 34-45
    CrossrefPubMedSearch in Google Scholar
  • 41 Jamilloux Y, Henry T, Belot A. et al. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun Rev 2020; 19 (07) 102567
    CrossrefPubMedSearch in Google Scholar
  • 42 Giamarellos-Bourboulis EJ, Netea MG, Rovina N. et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe 2020; 27 (06) 992-1000.e3
    CrossrefPubMedSearch in Google Scholar
  • 43 Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents 2020; 55 (05) 105954
    CrossrefPubMedSearch in Google Scholar
  • 44 Guan WJ, Ni ZY, Hu Y. China Medical Treatment Expert Group for Covid-19. et al; Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382 (18) 1708-1720
    CrossrefPubMedSearch in Google Scholar
  • 45 Zhu J, Ji P, Pang J. et al. Clinical characteristics of 3,062 COVID-19 patients: a meta-analysis. J Med Virol 2020;
    CrossrefPubMedSearch in Google Scholar
  • 46 Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020; 135 (23) 2033-2040
    CrossrefPubMedSearch in Google Scholar
  • 47 Chen G, Wu D, Guo W. et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest 2020; 130 (05) 2620-2629
    CrossrefPubMedSearch in Google Scholar
  • 48 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
    Search in Google Scholar
  • 49 Han H, Ma Q, Li C. et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect 2020; 9 (01) 1123-1130
    CrossrefPubMedSearch in Google Scholar
  • 50 Du H, Dong X, Zhang JJ. et al. Clinical characteristics of 182 pediatric COVID-19 patients with different severities and allergic status. Allergy 2020
    Search in Google Scholar
  • 51 Liu J, Li S, Liu J. et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020; 55: 102763
    CrossrefPubMedSearch in Google Scholar
  • 52 Wang Z, Yang B, Li Q, Wen L, Zhang R. Clinical features of 69 cases with coronavirus disease 2019 in Wuhan, China. Clin Infect Dis 2020; ciaa272
    PubMedSearch in Google Scholar
  • 53 Tan M, Liu Y, Zhou R. et al. Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China. Immunology 2020; 160 (03) 261-268
    CrossrefPubMedSearch in Google Scholar
  • 54 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; ciaa449
    PubMedSearch in Google Scholar
  • 55 Tocilizumab in COVID-19 Pneumonia (TOCIVID-19). Accessed July 29, 2020 at: https://ClinicalTrials.gov/show/NCT04317092
  • 56 Tocilizumab for Prevention of Respiratory Failure in Patients With Severe COVID-19 Infection. Accessed July 29, 2020 at: https://ClinicalTrials.gov/show/NCT04377659
  • 57 Efficacy of Early Administration of Tocilizumab in COVID-19 Patients. Accessed July 29, 2020 at: https://ClinicalTrials.gov/show/NCT04346355
  • 58 Tocilizumab in the Treatment of Coronavirus Induced Disease (COVID-19). Accessed July 29, 2020 at: https://ClinicalTrials.gov/show/NCT04335071
  • 59 Premkumar M, Saxena P, Rangegowda D. et al. Coagulation failure is associated with bleeding events and clinical outcome during systemic inflammatory response and sepsis in acute-on-chronic liver failure: an observational cohort study. Liver Int 2019; 39 (04) 694-704
    CrossrefPubMedSearch in Google Scholar
  • 60 Mojiri A, Nakhaii-Nejad M, Phan WL. et al. Hypoxia results in upregulation and de novo activation of von Willebrand factor expression in lung endothelial cells. Arterioscler Thromb Vasc Biol 2013; 33 (06) 1329-1338
    CrossrefPubMedSearch in Google Scholar
  • 61 Matsuura Y, Yamashita A, Iwakiri T. et al. Vascular wall hypoxia promotes arterial thrombus formation via augmentation of vascular thrombogenicity. Thromb Haemost 2015; 114 (01) 158-172
    Thieme ConnectPubMedSearch in Google Scholar
  • 62 Ogawa S, Clauss M, Kuwabara K. et al. Hypoxia induces endothelial cell synthesis of membrane-associated proteins. Proc Natl Acad Sci U S A 1991; 88 (21) 9897-9901
    CrossrefPubMedSearch in Google Scholar
  • 63 Fearns C, Loskutoff DJ. Induction of plasminogen activator inhibitor 1 gene expression in murine liver by lipopolysaccharide. Cellular localization and role of endogenous tumor necrosis factor-alpha. Am J Pathol 1997; 150 (02) 579-590
    Search in Google Scholar
  • 64 Katneni UK, Ibla JC, Hunt R, Schiller T, Kimchi-Sarfaty C. von Willebrand factor/ADAMTS-13 interactions at birth: implications for thrombosis in the neonatal period. J Thromb Haemost 2019; 17 (03) 429-440
    CrossrefPubMedSearch in Google Scholar
  • 65 Bryckaert M, Rosa JP, Denis CV, Lenting PJ. Of von Willebrand factor and platelets. Cell Mol Life Sci 2015; 72 (02) 307-326
    CrossrefPubMedSearch in Google Scholar
  • 66 Zheng XL. ADAMTS13 and von Willebrand factor in thrombotic thrombocytopenic purpura. Annu Rev Med 2015; 66: 211-225
    CrossrefPubMedSearch in Google Scholar
  • 67 Stockschlaeder M, Schneppenheim R, Budde U. Update on von Willebrand factor multimers: focus on high-molecular-weight multimers and their role in hemostasis. Blood Coagul Fibrinolysis 2014; 25 (03) 206-216
    CrossrefPubMedSearch in Google Scholar
  • 68 Mannucci PM, Capoferri C, Canciani MT. Plasma levels of von Willebrand factor regulate ADAMTS-13, its major cleaving protease. Br J Haematol 2004; 126 (02) 213-218
    CrossrefPubMedSearch in Google Scholar
  • 69 Reiter RA, Knöbl P, Varadi K, Turecek PL. Changes in von Willebrand factor-cleaving protease (ADAMTS13) activity after infusion of desmopressin. Blood 2003; 101 (03) 946-948
    CrossrefPubMedSearch in Google Scholar
  • 70 Reiter RA, Varadi K, Turecek PL, Jilma B, Knöbl P. Changes in ADAMTS13 (von-Willebrand-factor-cleaving protease) activity after induced release of von Willebrand factor during acute systemic inflammation. Thromb Haemost 2005; 93 (03) 554-558
    Thieme ConnectPubMedSearch in Google Scholar
  • 71 Sonneveld MA, de Maat MP, Leebeek FW. Von Willebrand factor and ADAMTS13 in arterial thrombosis: a systematic review and meta-analysis. Blood Rev 2014; 28 (04) 167-178
    CrossrefPubMedSearch in Google Scholar
  • 72 Bongers TN, de Maat MP, van Goor ML. et al. High von Willebrand factor levels increase the risk of first ischemic stroke: influence of ADAMTS13, inflammation, and genetic variability. Stroke 2006; 37 (11) 2672-2677
    CrossrefPubMedSearch in Google Scholar
  • 73 Sonneveld MA, de Maat MP, Portegies ML. et al. Low ADAMTS13 activity is associated with an increased risk of ischemic stroke. Blood 2015; 126 (25) 2739-2746
    CrossrefPubMedSearch in Google Scholar
  • 74 Lambers M, Goldenberg NA, Kenet G. et al. Role of reduced ADAMTS13 in arterial ischemic stroke: a pediatric cohort study. Ann Neurol 2013; 73 (01) 58-64
    CrossrefPubMedSearch in Google Scholar
  • 75 Hunt R, Hoffman CM, Emani S. et al. Elevated preoperative von Willebrand factor is associated with perioperative thrombosis in infants and neonates with congenital heart disease. J Thromb Haemost 2017; 15 (12) 2306-2316
    CrossrefPubMedSearch in Google Scholar
  • 76 Andersson HM, Siegerink B, Luken BM. et al. High VWF, low ADAMTS13, and oral contraceptives increase the risk of ischemic stroke and myocardial infarction in young women. Blood 2012; 119 (06) 1555-1560
    CrossrefPubMedSearch in Google Scholar
  • 77 Gragnano F, Sperlongano S, Golia E. et al. The role of von Willebrand factor in vascular inflammation: from pathogenesis to targeted therapy. Mediators Inflamm 2017; 2017: 5620314
    CrossrefPubMedSearch in Google Scholar
  • 78 Hyseni A, Kemperman H, de Lange DW, Kesecioglu J, de Groot PG, Roest M. Active von Willebrand factor predicts 28-day mortality in patients with systemic inflammatory response syndrome. Blood 2014; 123 (14) 2153-2156
    CrossrefPubMedSearch in Google Scholar
  • 79 Bernardo A, Ball C, Nolasco L, Moake JF, Dong JF. Effects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flow. Blood 2004; 104 (01) 100-106
    CrossrefPubMedSearch in Google Scholar
  • 80 Chauhan AK, Kisucka J, Brill A, Walsh MT, Scheiflinger F, Wagner DD. ADAMTS13: a new link between thrombosis and inflammation. J Exp Med 2008; 205 (09) 2065-2074
    CrossrefPubMedSearch in Google Scholar
  • 81 Bockmeyer CL, Claus RA, Budde U. et al. Inflammation-associated ADAMTS13 deficiency promotes formation of ultra-large von Willebrand factor. Haematologica 2008; 93 (01) 137-140
    CrossrefPubMedSearch in Google Scholar
  • 82 Reuken PA, Kussmann A, Kiehntopf M. et al. Imbalance of von Willebrand factor and its cleaving protease ADAMTS13 during systemic inflammation superimposed on advanced cirrhosis. Liver Int 2015; 35 (01) 37-45
    CrossrefPubMedSearch in Google Scholar
  • 83 Kremer Hovinga JA, Zeerleder S, Kessler P. et al. ADAMTS-13, von Willebrand factor and related parameters in severe sepsis and septic shock. J Thromb Haemost 2007; 5 (11) 2284-2290
    CrossrefPubMedSearch in Google Scholar
  • 84 Bongers TN, Emonts M, de Maat MP. et al. Reduced ADAMTS13 in children with severe meningococcal sepsis is associated with severity and outcome. Thromb Haemost 2010; 103 (06) 1181-1187
    Thieme ConnectPubMedSearch in Google Scholar
  • 85 Karim F, Adil SN, Afaq B, Ul Haq A. Deficiency of ADAMTS-13 in pediatric patients with severe sepsis and impact on in-hospital mortality. BMC Pediatr 2013; 13 (01) 44
    CrossrefPubMedSearch in Google Scholar
  • 86 Fukushima H, Nishio K, Asai H. et al. Ratio of von Willebrand factor propeptide to ADAMTS13 is associated with severity of sepsis. Shock 2013; 39 (05) 409-414
    CrossrefPubMedSearch in Google Scholar
  • 87 Hyun J, Kim HK, Kim JE. et al. Correlation between plasma activity of ADAMTS-13 and coagulopathy, and prognosis in disseminated intravascular coagulation. Thromb Res 2009; 124 (01) 75-79
    CrossrefPubMedSearch in Google Scholar
  • 88 Habe K, Wada H, Ito-Habe N. et al. Plasma ADAMTS13, von Willebrand factor (VWF) and VWF propeptide profiles in patients with DIC and related diseases. Thromb Res 2012; 129 (05) 598-602
    CrossrefPubMedSearch in Google Scholar
  • 89 Vardavas CI, Nikitara K. COVID-19 and smoking: a systematic review of the evidence. Tob Induc Dis 2020; 18: 20
    CrossrefPubMedSearch in Google Scholar
  • 90 Ma Q, Jacobi PM, Emmer BT. et al. Genetic variants in ADAMTS13 as well as smoking are major determinants of plasma ADAMTS13 levels. Blood Adv 2017; 1 (15) 1037-1046
    CrossrefPubMedSearch in Google Scholar
  • 91 Leung JM, Yang CX, Tam A. et al. ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19. Eur Respir J 2020; 55 (05) 2000688
    CrossrefPubMedSearch in Google Scholar
  • 92 Barigye O. Smoking and inflammation. PLoS Med 2005; 2 (06) e198
    CrossrefPubMedSearch in Google Scholar
  • 93 Schwameis M, Schörgenhofer C, Assinger A, Steiner MM, Jilma B. VWF excess and ADAMTS13 deficiency: a unifying pathomechanism linking inflammation to thrombosis in DIC, malaria, and TTP. Thromb Haemost 2015; 113 (04) 708-718
    Thieme ConnectPubMedSearch in Google Scholar
  • 94 Wang A, Liu F, Dong N. et al. Thrombospondin-1 and ADAMTS13 competitively bind to VWF A2 and A3 domains in vitro. Thromb Res 2010; 126 (04) e260-e265
    CrossrefPubMedSearch in Google Scholar
  • 95 Bonnefoy A, Daenens K, Feys HB. et al. Thrombospondin-1 controls vascular platelet recruitment and thrombus adherence in mice by protecting (sub)endothelial VWF from cleavage by ADAMTS13. Blood 2006; 107 (03) 955-964
    CrossrefPubMedSearch in Google Scholar
  • 96 Pillai VG, Bao J, Zander CB. et al. Human neutrophil peptides inhibit cleavage of von Willebrand factor by ADAMTS13: a potential link of inflammation to TTP. Blood 2016; 128 (01) 110-119
    CrossrefPubMedSearch in Google Scholar
  • 97 Chen J, Fu X, Wang Y. et al. Oxidative modification of von Willebrand factor by neutrophil oxidants inhibits its cleavage by ADAMTS13. Blood 2010; 115 (03) 706-712
    CrossrefPubMedSearch in Google Scholar
  • 98 Crawley JT, Lam JK, Rance JB, Mollica LR, O'Donnell JS, Lane DA. Proteolytic inactivation of ADAMTS13 by thrombin and plasmin. Blood 2005; 105 (03) 1085-1093
    CrossrefPubMedSearch in Google Scholar
  • 99 Ono T, Mimuro J, Madoiwa S. et al. Severe secondary deficiency of von Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure. Blood 2006; 107 (02) 528-534
    CrossrefPubMedSearch in Google Scholar
  • 100 Liu C, Zhao L, Zhao J, Xu Q, Song Y, Wang H. Reduced ADAMTS-13 level negatively correlates with inflammation factors in plasma of acute myeloid leukemia patients. Leuk Res 2017; 53: 57-64
    CrossrefPubMedSearch in Google Scholar
  • 101 Takaya H, Kawaratani H, Kubo T. et al. Platelet hyperaggregability is associated with decreased ADAMTS13 activity and enhanced endotoxemia in patients with acute cholangitis. Hepatol Res 2018; 48 (03) E52-E60
    CrossrefPubMedSearch in Google Scholar
  • 102 Takaya H, Yoshiji H, Kawaratani H. et al. Decreased activity of plasma ADAMTS13 are related to enhanced cytokinemia and endotoxemia in patients with acute liver failure. Biomed Rep 2017; 7 (03) 277-285
    CrossrefPubMedSearch in Google Scholar
  • 103 Chen J, Chung DW. Inflammation, von Willebrand factor, and ADAMTS13. Blood 2018; 132 (02) 141-147
    CrossrefPubMedSearch in Google Scholar
  • 104 Bazzan M, Montaruli B, Sciascia S, Cosseddu D, Norbiato C, Roccatello D. Low ADAMTS 13 plasma levels are predictors of mortality in COVID-19 patients. Intern Emerg Med 2020
    Search in Google Scholar
  • 105 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
    Search in Google Scholar
  • 106 Adam EH, Zacharowski K, Miesbach W. A comprehensive assessment of the coagulation profile in critically ill COVID-19 patients. Thromb Res 2020; 194: 42-44
    CrossrefPubMedSearch in Google Scholar
  • 107 Latimer G, Corriveau C, DeBiasi RL. et al. Cardiac dysfunction and thrombocytopenia-associated multiple organ failure inflammation phenotype in a severe paediatric case of COVID-19. Lancet Child Adolesc Health 2020; 4 (07) 552-554
    CrossrefPubMedSearch in Google Scholar
  • 108 Escher R, Breakey N, Lämmle B. ADAMTS13 activity, von Willebrand factor, factor VIII and D-dimers in COVID-19 inpatients. Thromb Res 2020; 192: 174-175
    CrossrefPubMedSearch in Google Scholar
  • 109 Escher R, Breakey N, Lämmle B. Severe COVID-19 infection associated with endothelial activation. Thromb Res 2020; 190: 62
    CrossrefPubMedSearch in Google Scholar
  • 110 Lee SJ, Kim JE, Han KS, Kim HK. Thrombotic risk of reduced ADAMTS13 activity in patients with antiphospholipid antibodies. Blood Coagul Fibrinolysis 2016; 27 (08) 907-912
    CrossrefPubMedSearch in Google Scholar
  • 111 Galeano-Valle F, Oblitas CM, Ferreiro-Mazón MM. et al. Antiphospholipid antibodies are not elevated in patients with severe COVID-19 pneumonia and venous thromboembolism. Thromb Res 2020; 192: 113-115
    CrossrefPubMedSearch in Google Scholar
  • 112 Bowles L, Platton S, Yartey N. et al. Lupus anticoagulant and abnormal coagulation tests in patients with Covid-19. N Engl J Med 2020; 383 (03) 288-290
    CrossrefPubMedSearch in Google Scholar
  • 113 Austin SK, Starke RD, Lawrie AS, Cohen H, Machin SJ, Mackie IJ. The VWF/ADAMTS13 axis in the antiphospholipid syndrome: ADAMTS13 antibodies and ADAMTS13 dysfunction. Br J Haematol 2008; 141 (04) 536-544
    CrossrefPubMedSearch in Google Scholar
  • 114 Jian C, Xiao J, Gong L. et al. Gain-of-function ADAMTS13 variants that are resistant to autoantibodies against ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura. Blood 2012; 119 (16) 3836-3843
    CrossrefPubMedSearch in Google Scholar
  • 115 Lorenzo-Villalba N, Zulfiqar AA, Auburtin M. et al. Thrombocytopenia in the course of COVID-19 infection. Eur J Case Rep Intern Med 2020; 7 (06) 001702
    PubMedSearch in Google Scholar
  • 116 Yin S, Huang M, Li D, Tang N. Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2. J Thromb Thrombolysis 2020;
    CrossrefPubMedSearch in Google Scholar
  • 117 Demelo-Rodríguez P, Cervilla-Muñoz E, Ordieres-Ortega L. et al. Incidence of asymptomatic deep vein thrombosis in patients with COVID-19 pneumonia and elevated D-dimer levels. Thromb Res 2020; 192: 23-26
    CrossrefPubMedSearch in Google Scholar
  • 118 Grandmaison G, Andrey A, Périard D. et al. Systematic screening for venous thromboembolic events in COVID-19 pneumonia. TH Open 2020; 4 (02) e113-e115
    Thieme ConnectPubMedSearch in Google Scholar
  • 119 Fraissé M, Logre E, Pajot O, Mentec H, Plantefève G, Contou D. Thrombotic and hemorrhagic events in critically ill COVID-19 patients: a French monocenter retrospective study. Crit Care 2020; 24 (01) 275
    CrossrefPubMedSearch in Google Scholar
  • 120 Bastiani G, Valle MT. Determination of factor XII in blood products and correction of its deficiency after plasma transfusion in a case [in Italian]. Haematologica 1979; 64 (05) 635-640
    PubMedSearch in Google Scholar
  • 121 Desborough MJR, Doyle AJ, Griffiths A, Retter A, Breen KA, Hunt BJ. Image-proven thromboembolism in patients with severe COVID-19 in a tertiary critical care unit in the United Kingdom. Thromb Res 2020; 193: 1-4
    CrossrefPubMedSearch in Google Scholar
  • 122 Akel T, Qaqa F, Abuarqoub A, Shamoon F. Pulmonary embolism: a complication of COVID 19 infection. Thromb Res 2020; 193: 79-82
    CrossrefPubMedSearch in Google Scholar
  • 123 Kashi M, Jacquin A, Dakhil B. et al. Severe arterial thrombosis associated with Covid-19 infection. Thromb Res 2020; 192: 75-77
    CrossrefPubMedSearch in Google Scholar
  • 124 Lax SF, Skok K, Zechner P. et al. Pulmonary arterial thrombosis in COVID-19 with fatal outcome: results from a prospective, single-center, clinicopathologic case series. Ann Intern Med 2020; 173 (05) 350-361
    CrossrefPubMedSearch in Google Scholar
  • 125 Thomas W, Varley J, Johnston A. et al. Thrombotic complications of patients admitted to intensive care with COVID-19 at a teaching hospital in the United Kingdom. Thromb Res 2020; 191: 76-77
    CrossrefPubMedSearch in Google Scholar
  • 126 Gomez-Arbelaez D, Ibarra-Sanchez G, Garcia-Gutierrez A, Comanges-Yeboles A, Ansuategui-Vicente M, Gonzalez-Fajardo JA. COVID-19-related aortic thrombosis: a report of four cases. Ann Vasc Surg 2020; S0890-5096(20)30438-6
    PubMedSearch in Google Scholar
  • 127 Ayerbe L, Risco C, Ayis S. The association between treatment with heparin and survival in patients with Covid-19. J Thromb Thrombolysis 2020; 50 (02) 298-301
    CrossrefPubMedSearch in Google Scholar
  • 128 Wang T, Chen R, Liu C. et al. Attention should be paid to venous thromboembolism prophylaxis in the management of COVID-19. Lancet Haematol 2020; 7 (05) e362-e363
    Search in Google Scholar
  • 129 Artifoni M, Danic G, Gautier G. et al. Systematic assessment of venous thromboembolism in COVID-19 patients receiving thromboprophylaxis: incidence and role of D-dimer as predictive factors. J Thromb Thrombolysis 2020; 50 (01) 211-216
    CrossrefPubMedSearch in Google Scholar
  • 130 Russo V, Di Maio M, Attena E. et al. Clinical impact of pre-admission antithrombotic therapy in hospitalized patients with COVID-19: a multicenter observational study. Pharmacol Res 2020; 159: 104965
    CrossrefPubMedSearch in Google Scholar
  • 131 Maier CL, Truong AD, Auld SC, Polly DM, Tanksley CL, Duncan A. COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia?. Lancet 2020; 395 (10239): 1758-1759
    CrossrefPubMedSearch in Google Scholar
  • 132 Magro C, Mulvey JJ, Berlin D. et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases. Transl Res 2020; 220: 1-13
    CrossrefPubMedSearch in Google Scholar