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Thromb Haemost 2020; 120(07): 1004-1024
DOI: 10.1055/s-0040-1713152
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Pharmacological Agents Targeting Thromboinflammation in COVID-19: Review and Implications for Future Research

Behnood Bikdeli   *
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
2   Center for Outcomes Research and Evaluation (CORE), Yale School of Medicine, New Haven, Connecticut, United States
3   Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Mahesh V. Madhavan‡   *
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
3   Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Aakriti Gupta
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
2   Center for Outcomes Research and Evaluation (CORE), Yale School of Medicine, New Haven, Connecticut, United States
3   Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
David Jimenez
4   Respiratory Department, Hospital Ramón y Cajal, Madrid, Spain
5   Medicine Department, Universidad de Alcalá (IRYCIS), CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain
,
John R. Burton
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
,
Caroline Der Nigoghossian
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
,
Taylor Chuich
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
,
Shayan Nabavi Nouri
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
,
Isaac Dreyfus
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
,
Elissa Driggin
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
,
Sanjum Sethi
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
,
Kartik Sehgal
6   Harvard Medical School, Boston, Massachusetts, United States
7   Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
,
Saurav Chatterjee
8   North Shore and Long Island Jewish University Hospitals, Queens, New York, United States
,
Walter Ageno
9   Department of Medicine and Surgery, University of Insubria, Varese, Italy
,
Mohammad Madjid
10   McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, United States
,
Yutao Guo 
11   Department of Cardiology, Chinese PLA General Hospital, Beijing, China
12   Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
,
Liang V. Tang
13   Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Yu Hu
13   Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Laurent Bertoletti 
14   Department of “Médecine Vasculaire et Thérapeutique,” CIC 1408, INNOVTE, CHU de St-Etienne and INSERM UMR1059, Université Jean-Monnet, Saint-Etienne, France
,
Jay Giri
15   Cardiovascular Division, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States
16   Penn Cardiovascular Outcomes, Quality, and Evaluative Research Center, Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania, United States
17   Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, United States
,
Mary Cushman
18   Larner College of Medicine, University of Vermont, Burlington, Vermont, United States
,
Isabelle Quéré
19   Department of Vascular Medicine, University of Montpellier, Montpellier CHU, InnoVTE F-CRIN Network, Montpellier, France
,
Evangelos P. Dimakakos
20   Oncology Unit GPP, Sotiria General Hospital, Athens School of Medicine, Athens, Greece
,
C. Michael Gibson
6   Harvard Medical School, Boston, Massachusetts, United States
7   Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
,
Giuseppe Lippi
21   Laboratory of Clinical Chemistry and Hematology, University Hospital of Verona, Verona, Italy
,
Emmanuel J. Favaloro
22   Laboratory Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia
23   Sydney Centres for Thrombosis and Haemostasis, Westmead, NSW, Australia
,
Jawed Fareed
24   Loyola University Medical Center, Chicago, Illinois, United States
,
Alfonso J. Tafur
25   Pritzker School of Medicine at the University of Chicago, Chicago, Illinois, United States
26   Division of Vascular Medicine, Department of Medicine, NorthShore University HealthSystem, Skokie, Illinois, United States
,
Dominic P. Francese
3   Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Jaya Batra
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
,
Anna Falanga
27   Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, University of Milan Bicocca, Bergamo, Italy
,
Kevin J. Clerkin
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
,
Nir Uriel
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
,
Ajay Kirtane
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
3   Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Claire McLintock
28   Auckland City Hospital, Auckland, New Zealand
,
Beverley J. Hunt
29   St Thomas' Hospital, London, United Kingdom
,
Alex C. Spyropoulos
30   The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, New York, United States
,
Geoffrey D. Barnes
31   Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, Michigan, United States
32   Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, United States
,
John W. Eikelboom
33   Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
,
Ido Weinberg
6   Harvard Medical School, Boston, Massachusetts, United States
34   Massachusetts General Hospital, Boston, Massachusetts, United States
,
Sam Schulman
35   Department of Obstetrics and Gynecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
36   McMaster University, Hamilton, Ontario, Canada
37   Thrombosis & Atherosclerosis Research Institute, Hamilton, Ontario, Canada
,
Marc Carrier
38   The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
,
Gregory Piazza
6   Harvard Medical School, Boston, Massachusetts, United States
39   Brigham and Women's Hospital, Boston, Massachusetts, United States
,
Joshua A. Beckman
40   Vanderbilt University School of Medicine, Nashville, Tennessee, United States
,
Martin B. Leon
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
3   Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Gregg W. Stone
3   Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
41   The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States
,
Stephan Rosenkranz
42   Department of Cardiology, Cologne Cardiovascular Research Center (CCRC), Heart Center at the University of Cologne, University of Cologne, Cologne, Germany
,
Samuel Z. Goldhaber
6   Harvard Medical School, Boston, Massachusetts, United States
39   Brigham and Women's Hospital, Boston, Massachusetts, United States
,
Sahil A. Parikh
1   New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States
3   Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States
,
Manuel Monreal
43   Department of Internal Medicine, Hospital Universitari Germans Trials I Pujol, Universidad Católica de Murcia, Barcelona, Spain
,
Harlan M. Krumholz
2   Center for Outcomes Research and Evaluation (CORE), Yale School of Medicine, New Haven, Connecticut, United States
44   Department of Health Policy and Administration, Yale School of Public Health, New Haven, Connecticut, United States
45   Section of Cardiovascular Medicine, Department of Internal Medicie, Yale School of Medicine, New Haven, Connecticut, United States
,
Stavros V. Konstantinides 
46   Center for Thrombosis and Hemostasis, Johannes Gutenberg University of Mainz, Mainz, Germany
,
Jeffrey I. Weitz
36   McMaster University, Hamilton, Ontario, Canada
37   Thrombosis & Atherosclerosis Research Institute, Hamilton, Ontario, Canada
,
Gregory Y. H. Lip 
12   Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
47   Department of Clinical Medicine, Aalborg Thrombosis Research Unit, Aalborg University, Aalborg, Denmark
,
The Global COVID-19 Thrombosis Collaborative Group › Author Affiliations
Further Information

Publication History

15 May 2020

15 May 2020

Publication Date:
30 May 2020 (online)

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Abstract

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.

Keywords

coronavirus disease 2019 - thrombosis - inflammation - fibrinolytic therapy - anticoagulation - immunomodulator - antithrombin - thrombomodulin

* Drs. Bikdeli and Madhavan contributed equally to this manuscript.


Supplementary Material

 

  • References

  • 1 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
  • 2 World Health Organization. WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020. Available at: https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19—11-march-2020 . Accessed March 12, 2020
    PubMed
  • 3 Driggin E, Madhavan MV, Bikdeli B. , et al. Cardiovascular considerations for patients, health care workers, and health systems during the coronavirus disease 2019 (COVID-19) pandemic. J Am Coll Cardiol 2020; 75 (18): 2352-2371
    PubMedSearch in Google Scholar
  • 4 Clerkin KJ, Fried JA, Raikhelkar J. , et al. COVID-19 and cardiovascular disease. Circulation 2020; 141 (20) 1648-1655
    CrossrefPubMedSearch in Google Scholar
  • 5 Bikdeli B, Madhavan MV, Jimenez D. , et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol 2020 . Doi: 10.1016/j.jacc.2020.04.031
    PubMedSearch in Google Scholar
  • 6 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
    PubMedSearch in Google Scholar
  • 7 Klok FA, Kruip M, van der Meer NJM. , et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020;
    CrossrefPubMedSearch in Google Scholar
  • 8 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; 1-10 . Doi: 10.1007/s00134-020-06062-x
    PubMedSearch in Google Scholar
  • 9 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
    CrossrefPubMedSearch in Google Scholar
  • 10 Bangalore S, Sharma A, Slotwiner A. , et al. ST-segment elevation in patients with Covid-19 - a case series. N Engl J Med 2020 . Doi: 10.1056/NEJMc2009020
    PubMedSearch in Google Scholar
  • 11 Bellosta R, Luzzani L, Natalini G. , et al. Acute limb ischemia in patients with COVID-19 pneumonia. J Vasc Surg 2020 . Doi: 10.1016/j.jvs.2020.04.483
    PubMedSearch in Google Scholar
  • 12 Akima S, McLintock C, Hunt BJRE. RE: ISTH interim guidance to recognition and management of coagulopathy in COVID-19. J Thromb Haemost 2020 . Doi: 10.1111/jth.14853
    PubMedSearch in Google Scholar
  • 13 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 . Doi: 10.1111/jth.14860
    PubMedSearch in Google Scholar
  • 14 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(5):1023–1026
    PubMed
  • 15 Zhai Z, Li C, Chen Y. , et al; Prevention Treatment of VTE Associated with COVID-19 Infection Consensus Statement Group. Prevention and treatment of venous thromboembolism associated with coronavirus disease 2019 infection: a consensus statement before guidelines. Thromb Haemost 2020 . Doi: 10.1055/s-0040-1710019
    PubMedSearch in Google Scholar
  • 16 Vivas D, Roldan V, Esteve-Pastor MA. , et al. Recommendations on antithrombotic treatment during the COVID-19 pandemic. Position statement of the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology. Rev Esp Cardiol 2020 . Doi: 10.1016/j.recesp.2020.04.006
    PubMedSearch in Google Scholar
  • 17 Marietta M, Ageno W, Artoni A. , et al. COVID-19 and haemostasis: a position paper from Italian Society on Thrombosis and Haemostasis (SISET). Blood Transfus 2020 . Doi: 10.2450/2020.0083-20
    PubMedSearch in Google Scholar
  • 18 Casini A, Alberio L, Angelillo-Scherrer A. , et al. Thromboprophylaxis and laboratory monitoring for in-hospital patients with COVID-19 - a Swiss consensus statement by the Working Party Hemostasis. Swiss Med Wkly 2020; 150: w20247
    PubMedSearch in Google Scholar
  • 19 Murao S, Yamakawa K. A systematic summary of systematic reviews on anticoagulant therapy in sepsis. J Clin Med 2019; 8 (11) E1869
    CrossrefPubMedSearch in Google Scholar
  • 20 Campbell CM, Kahwash R. Will complement inhibition be the new target in treating COVID-19 related systemic thrombosis?. Circulation 2020 . Doi: 10.1161/CIRCULATIONAHA.120.047419
    PubMedSearch in Google Scholar
  • 21 Thachil J. The versatile heparin in COVID-19. J Thromb Haemost 2020; 18 (05) 1020-1022
    CrossrefPubMedSearch in Google Scholar
  • 22 Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (02) e24S-e43S
    CrossrefPubMedSearch in Google Scholar
  • 23 Poterucha TJ, Libby P, Goldhaber SZ. More than an anticoagulant: do heparins have direct anti-inflammatory effects?. Thromb Haemost 2017; 117 (03) 437-444
    Thieme ConnectPubMedSearch in Google Scholar
  • 24 Belen-Apak FB, Sarialioglu F. The old but new: can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARS-CoV2 by inhibition of host cell proteases?. Med Hypotheses 2020; 142: 109743
    CrossrefPubMedSearch in Google Scholar
  • 25 Liu J, Li J, Arnold K. , et al. Using heparin molecules to manage COVID-2019. Res Pract Thromb Haemost 2020 . Doi: 10.1002/rth2.12353
    PubMedSearch in Google Scholar
  • 26 Obi AT, Tignanelli CJ, Jacobs BN. , et al. Empirical systemic anticoagulation is associated with decreased venous thromboembolism in critically ill influenza A H1N1 acute respiratory distress syndrome patients. J Vasc Surg Venous Lymphat Disord 2019; 7 (03) 317-324
    CrossrefPubMedSearch in Google Scholar
  • 27 Obi AT, Barnes GD, Wakefield TW. , et al. Practical diagnosis and treatment of suspected venous thromboembolism during COVID-19 pandemic. J Vasc Surg Venous Lymphat Disord 2020; S2213-333X(20)30221-3
    PubMedSearch in Google Scholar
  • 28 Cohoon KP, Mahé G, Tafur AJ. , et al. Emergence of institutional antithrombotic protocols for coronavirus. Res Pract Thromb Haemost 2019 . Doi: 10.1002/rth2.12358
    PubMedSearch in Google Scholar
  • 29 Eikelboom JW, Hirsh J. Monitoring unfractionated heparin with the aPTT: time for a fresh look. Thromb Haemost 2006; 96 (05) 547-552
    Thieme ConnectPubMedSearch in Google Scholar
  • 30 Bowles L, Platton S, Yartey N. , et al. Lupus anticoagulant and abnormal coagulation tests in patients with Covid-19. N Engl J Med 2020 . Doi: 10.1056/NEJMc2013656
    PubMedSearch in Google Scholar
  • 31 Vandiver JW, Vondracek TG. Antifactor Xa levels versus activated partial thromboplastin time for monitoring unfractionated heparin. Pharmacotherapy 2012; 32 (06) 546-558
    CrossrefPubMedSearch in Google Scholar
  • 32 Mycroft-West C, Su D, Elli S, et al. The 2019 coronavirus (SARSCoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding. bio-Rxiv 2020: 2020.02.29.971093
    PubMed
  • 33 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) 271-280
    CrossrefPubMedSearch in Google Scholar
  • 34 Shang J, Ye G, Shi K. , et al. Structural basis of receptor recognition by SARS-CoV-2. Nature 2020; 581 (7807): 221-224
    CrossrefPubMedSearch in Google Scholar
  • 35 Lang J, Yang N, Deng J. , et al. Inhibition of SARS pseudovirus cell entry by lactoferrin binding to heparan sulfate proteoglycans. PLoS One 2011; 6 (08) e23710
    CrossrefPubMedSearch in Google Scholar
  • 36 Dou H, Song A, Jia S, Zhang L. Heparinoids danaparoid and sulodexide as clinically used drugs. Prog Mol Biol Transl Sci 2019; 163: 55-74
    PubMedSearch in Google Scholar
  • 37 Frantzeskaki F, Armaganidis A, Orfanos SE. Immunothrombosis in acute respiratory distress syndrome: cross talks between inflammation and coagulation. Respiration 2017; 93 (03) 212-225
    CrossrefPubMedSearch in Google Scholar
  • 38 Warkentin TE. Heparin-induced thrombocytopenia in critically ill patients. Semin Thromb Hemost 2015; 41 (01) 49-60
    Thieme ConnectPubMedSearch in Google Scholar
  • 39 Decousus H, Tapson VF, Bergmann JF. , et al; IMPROVE Investigators. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest 2011; 139 (01) 69-79
    CrossrefPubMedSearch in Google Scholar
  • 40 Burgess JK, Chong BH. The platelet proaggregating and potentiating effects of unfractionated heparin, low molecular weight heparin and heparinoid in intensive care patients and healthy controls. Eur J Haematol 1997; 58 (04) 279-285
    PubMedSearch in Google Scholar
  • 41 Minakata D, Fujiwara SI, Hayakawa J. , et al. Comparison of danaparoid sodium and synthetic protease inhibitors for the treatment of disseminated intravascular coagulation associated with hematological malignancies: a retrospective analysis. Acta Haematol 2019; 1-10
    PubMedSearch in Google Scholar
  • 42 Marongiu F, Grandone E, Barcellona D. Pulmonary thrombosis in 2019-nCoV pneumonia?. J Thromb Haemost 2020 . Doi: 10.1111/jth.14818
    PubMedSearch in Google Scholar
  • 43 Wichmann D, Sperhake JP, Lütgehetmann M. , et al. Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study. Ann Intern Med 2020 . Doi: 10.7326/M20-2003
    PubMedSearch in Google Scholar
  • 44 Hagiwara S, Iwasaka H, Hidaka S, Hishiyama S, Noguchi T. Danaparoid sodium inhibits systemic inflammation and prevents endotoxin-induced acute lung injury in rats. Crit Care 2008; 12 (02) R43
    CrossrefPubMedSearch in Google Scholar
  • 45 Iba T, Miyasho T. Danaparoid sodium attenuates the increase in inflammatory cytokines and preserves organ function in endotoxemic rats. Crit Care 2008; 12 (04) R86
    CrossrefPubMedSearch in Google Scholar
  • 46 Juschten J, Tuinman PR, Juffermans NP, Dixon B, Levi M, Schultz MJ. Nebulized anticoagulants in lung injury in critically ill patients-an updated systematic review of preclinical and clinical studies. Ann Transl Med 2017; 5 (22) 444
    PubMedSearch in Google Scholar
  • 47 Bikdeli B, McAndrew T, Crowley A. , et al. Individual patient data pooled analysis of randomized trials of bivalirudin versus heparin in acute myocardial infarction: rationale and methodology. Thromb Haemost 2020; 120 (02) 348-362
    Thieme ConnectPubMedSearch in Google Scholar
  • 48 Salter BS, Weiner MM, Trinh MA. , et al. Heparin-induced thrombocytopenia: a comprehensive clinical review. J Am Coll Cardiol 2016; 67 (21) 2519-2532
    CrossrefPubMedSearch in Google Scholar
  • 49 Schein JR, White CM, Nelson WW, Kluger J, Mearns ES, Coleman CI. Vitamin K antagonist use: evidence of the difficulty of achieving and maintaining target INR range and subsequent consequences. Thromb J 2016; 14: 14
    CrossrefPubMedSearch in Google Scholar
  • 50 Jose RJ, Manuel A. COVID-19 cytokine storm: the interplay between inflammation and coagulation. Lancet Respir Med 2020; S2213-2600(20)30216-2
    PubMedSearch in Google Scholar
  • 51 Mega JL, Braunwald E, Wiviott SD. , et al; ATLAS ACS 2–TIMI 51 Investigators. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012; 366 (01) 9-19
    CrossrefPubMedSearch in Google Scholar
  • 52 Eikelboom JW, Connolly SJ, Bosch J. , et al; COMPASS Investigators. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 2017; 377 (14) 1319-1330
    CrossrefPubMedSearch in Google Scholar
  • 53 Bonaca MP, Bauersachs RM, Anand SS. , et al. Rivaroxaban in peripheral artery disease after revascularization. N Engl J Med 2020; 382 (21) 1994-2004
    CrossrefPubMedSearch in Google Scholar
  • 54 Cohen AT, Spiro TE, Büller HR. , et al; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 2013; 368 (06) 513-523
    CrossrefPubMedSearch in Google Scholar
  • 55 Spyropoulos AC, Ageno W, Albers GW. , et al; MARINER Investigators. Rivaroxaban for thromboprophylaxis after hospitalization for medical illness. N Engl J Med 2018; 379 (12) 1118-1127
    CrossrefPubMedSearch in Google Scholar
  • 56 Cohen AT, Harrington RA, Goldhaber SZ. , et al; APEX Investigators. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med 2016; 375 (06) 534-544
    CrossrefPubMedSearch in Google Scholar
  • 57 Goldhaber SZ, Leizorovicz A, Kakkar AK. , et al; ADOPT Trial Investigators. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med 2011; 365 (23) 2167-2177
    CrossrefPubMedSearch in Google Scholar
  • 58 Spyropoulos AC, Lipardi C, Xu J. , et al. Improved benefit risk profile of rivaroxaban in a subpopulation of the MAGELLAN study. Clin Appl Thromb Hemost 2019; 25: 1076029619886022
    CrossrefPubMedSearch in Google Scholar
  • 59 Yang X, Yu Y, Xu J. , et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020; 8 (05) 475-481
    CrossrefPubMedSearch in Google Scholar
  • 60 Bhatraju PK, Ghassemieh BJ, Nichols M. , et al. Covid-19 in critically ill patients in the Seattle region - case series. N Engl J Med 2020; 382: 2012-2022
    CrossrefPubMedSearch in Google Scholar
  • 61 Testa S, Prandoni P, Paoletti O. , et al. Direct oral anticoagulant plasma levels' striking increase in severe COVID-19 respiratory syndrome patients treated with antiviral agents: the Cremona experience. J Thromb Haemost 2020 . Doi: 10.1111/jth.14871
    PubMedSearch in Google Scholar
  • 62 Kearon C, Akl EA, Ornelas J. , et al. Antithrombotic therapy for VTE Disease: CHEST guideline and expert panel report. Chest 2016; 149 (02) 315-352
    CrossrefPubMedSearch in Google Scholar
  • 63 Wu B, Lu J, Yang M, Xu T. Sulodexide for treating venous leg ulcers. Cochrane Database Syst Rev 2016; (06) CD010694
    PubMedSearch in Google Scholar
  • 64 Lasierra-Cirujeda J, Coronel P, Aza M, Gimeno M. Use of sulodexide in patients with peripheral vascular disease. J Blood Med 2010; 1: 105-115
    CrossrefPubMedSearch in Google Scholar
  • 65 Lauver DA, Lucchesi BR. Sulodexide: a renewed interest in this glycosaminoglycan. Cardiovasc Drug Rev 2006; 24 (3-4): 214-226
    CrossrefPubMedSearch in Google Scholar
  • 66 Mauro M, Palmieri GC, Palazzini E, Barbanti M, Calanni Rindina F, Milani MR. Pharmacodynamic effects of single and repeated doses of oral sulodexide in healthy volunteers. A placebo-controlled study with an enteric-coated formulation. Curr Med Res Opin 1993; 13 (02) 87-95
    CrossrefPubMedSearch in Google Scholar
  • 67 Femiano F, Gombos F, Scully C. Recurrent aphthous stomatitis unresponsive to topical corticosteroids: a study of the comparative therapeutic effects of systemic prednisone and systemic sulodexide. Int J Dermatol 2003; 42 (05) 394-397
    CrossrefPubMedSearch in Google Scholar
  • 68 Bilinska M, Wolszakiewicz J, Duda M, Janas J, Beresewicz A, Piotrowicz R. Antioxidative activity of sulodexide, a glycosaminoglycan, in patients with stable coronary artery disease: a pilot study. Med Sci Monit 2009; 15 (12) CR618-CR623
    PubMedSearch in Google Scholar
  • 69 Bikdeli B, Chatterjee S, Kirtane AJ. , et al. Sulodexide versus control and the risk of thrombotic and hemorrhagic events: meta-analysis of randomized trials. Semin Thromb Hemost 2020 (in press)
    PubMed
  • 70 Doctor gambles on clot-busting drug to save virus patients. Available at: https://apnews.com/5c0dc863f214d32a53c6280c31cf3f56 . Accessed April 20, 2020
    PubMed
  • 71 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 . Doi: 10.1111/jth.14828
    PubMedSearch in Google Scholar
  • 72 Barrett CD, Morre HB, Moore EE. , et al. Fibrinolytic therapy for refractory COVID 19 acute respiratory distress syndrome: scientific rationale and review. Research and practice in Thrombosis and Haemostasis 2020. . Available at: https://doi.org/10.1002/rth2.12357 . Accessed May 21, 2020
  • 73 Xu Z, Shi L, Wang Y. , et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; 8 (04) 420-422
    CrossrefPubMedSearch in Google Scholar
  • 74 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
    CrossrefPubMedSearch in Google Scholar
  • 75 Moore HB, Barrett CD, Moore EE. , et al. Is there a role for tissue plasminogen activator (tPA) as a novel treatment for refractory COVID-19 associated acute respiratory distress syndrome (ARDS)?. J Trauma Acute Care Surg 2020 . Doi: 10.1097/TA.0000000000002694
    PubMedSearch in Google Scholar
  • 76 Hardaway RM, Williams CH, Marvasti M. , et al. Prevention of adult respiratory distress syndrome with plasminogen activator in pigs. Crit Care Med 1990; 18 (12) 1413-1418
    CrossrefPubMedSearch in Google Scholar
  • 77 Stringer KA, Hybertson BM, Cho OJ, Cohen Z, Repine JE. Tissue plasminogen activator (tPA) inhibits interleukin-1 induced acute lung leak. Free Radic Biol Med 1998; 25 (02) 184-188
    CrossrefPubMedSearch in Google Scholar
  • 78 Liu C, Ma Y, Su Z. , et al. Meta-analysis of preclinical studies of fibrinolytic therapy for acute lung injury. Front Immunol 2018; 9: 1898
    CrossrefPubMedSearch in Google Scholar
  • 79 Hardaway RM, Harke H, Tyroch AH, Williams CH, Vazquez Y, Krause GF. Treatment of severe acute respiratory distress syndrome: a final report on a phase I study. Am Surg 2001; 67 (04) 377-382
    PubMedSearch in Google Scholar
  • 80 Abdelaal Ahmed Mahmoud A, Mahmoud HE, Mahran MA, Khaled M. Streptokinase versus unfractionated heparin nebulization in patients with severe acute respiratory distress syndrome (ARDS): a randomized controlled trial with observational controls. J Cardiothorac Vasc Anesth 2020; 34 (02) 436-443
    CrossrefPubMedSearch in Google Scholar
  • 81 Brass LM, Lichtman JH, Wang Y, Gurwitz JH, Radford MJ, Krumholz HM. Intracranial hemorrhage associated with thrombolytic therapy for elderly patients with acute myocardial infarction: results from the Cooperative Cardiovascular Project. Stroke 2000; 31 (08) 1802-1811
    CrossrefPubMedSearch in Google Scholar
  • 82 Wahlgren N, Ahmed N, Dávalos A. , et al; SITS-MOST investigators. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007; 369 (9558): 275-282
    CrossrefPubMedSearch in Google Scholar
  • 83 Chatterjee S, Weinberg I, Yeh RW. , et al. Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy development of the PE-CH score. Thromb Haemost 2017; 117 (02) 246-251
    Thieme ConnectPubMedSearch in Google Scholar
  • 84 Huang X, Moreton FC, Kalladka D. , et al. Coagulation and fibrinolytic activity of tenecteplase and alteplase in acute ischemic stroke. Stroke 2015; 46 (12) 3543-3546
    CrossrefPubMedSearch in Google Scholar
  • 85 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 . Doi: 10.1111/jth.14872
    PubMedSearch in Google Scholar
  • 86 Li H, Liu L, Zhang D. , et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet 2020; 395 (10235): 1517-1520
    CrossrefPubMedSearch in Google Scholar
  • 87 de Stoppelaar SF, van 't Veer C, van der Poll T. The role of platelets in sepsis. Thromb Haemost 2014; 112 (04) 666-677
    Thieme ConnectPubMedSearch in Google Scholar
  • 88 Koupenova M, Corkrey HA, Vitseva O. , et al. The role of platelets in mediating a response to human influenza infection. Nat Commun 2019; 10 (01) 1780
    CrossrefPubMedSearch in Google Scholar
  • 89 de Stoppelaar SF, van 't Veer C, Claushuis TA, Albersen BJ, Roelofs JJ, van der Poll T. Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice. Blood 2014; 124 (25) 3781-3790
    PubMedSearch in Google Scholar
  • 90 Semple JW, Italiano JE Jr, Freedman J. Platelets and the immune continuum. Nat Rev Immunol 2011;11(04):264–274
    PubMed
  • 91 Yeaman MR. Platelets in defense against bacterial pathogens. Cell Mol Life Sci 2010; 67 (04) 525-544
    CrossrefPubMedSearch in Google Scholar
  • 92 Xiang B, Zhang G, Guo L. , et al. Platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the cyclooxygenase 1 signalling pathway. Nat Commun 2013; 4 (01) 2657
    CrossrefPubMedSearch in Google Scholar
  • 93 Gudbrandsdottir S, Hasselbalch HC, Nielsen CH. Activated platelets enhance IL-10 secretion and reduce TNF-α secretion by monocytes. J Immunol 2013; 191 (08) 4059-4067
    CrossrefPubMedSearch in Google Scholar
  • 94 Zarbock A, Singbartl K, Ley K. Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation. J Clin Invest 2006; 116 (12) 3211-3219
    CrossrefPubMedSearch in Google Scholar
  • 95 Looney MR, Nguyen JX, Hu Y, Van Ziffle JA, Lowell CA, Matthay MA. Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury. J Clin Invest 2009; 119 (11) 3450-3461
    PubMedSearch in Google Scholar
  • 96 Wang L, Li H, Gu X, Wang Z, Liu S, Chen L. Effect of antiplatelet therapy on acute respiratory distress syndrome and mortality in critically ill patients: a meta-analysis. PLoS One 2016; 11 (05) e0154754
    CrossrefPubMedSearch in Google Scholar
  • 97 Boyle AJ, Di Gangi S, Hamid UI. , et al. Aspirin therapy in patients with acute respiratory distress syndrome (ARDS) is associated with reduced intensive care unit mortality: a prospective analysis. Crit Care 2015; 19 (01) 109
    CrossrefPubMedSearch in Google Scholar
  • 98 Chen W, Janz DR, Bastarache JA. , et al. Prehospital aspirin use is associated with reduced risk of acute respiratory distress syndrome in critically ill patients: a propensity-adjusted analysis. Crit Care Med 2015; 43 (04) 801-807
    CrossrefPubMedSearch in Google Scholar
  • 99 Panka BA, de Grooth HJ, Spoelstra-de Man AM, Looney MR, Tuinman PR. Prevention or treatment of ARDS with aspirin: a review of preclinical models and meta-analysis of clinical studies. Shock 2017; 47 (01) 13-21
    CrossrefPubMedSearch in Google Scholar
  • 100 Kor DJ, Carter RE, Park PK. , et al; US Critical Illness and Injury Trials Group: Lung Injury Prevention with Aspirin Study Group (USCIITG: LIPS-A). Effect of aspirin on development of ARDS in at-risk patients presenting to the emergency department: the LIPS-A randomized clinical trial. JAMA 2016; 315 (22) 2406-2414
    CrossrefPubMedSearch in Google Scholar
  • 101 Kuschner RA. Aspirin and acute respiratory distress syndrome. JAMA 2016; 316 (12) 1317-1318
    PubMedSearch in Google Scholar
  • 102 Mezidi M, Guérin C. Aspirin for prevention of acute respiratory distress syndrome (ARDS): let's not throw the baby with the water!. Ann Transl Med 2016; 4 (19) 376
    CrossrefPubMedSearch in Google Scholar
  • 103 Gross AK, Dunn SP, Feola DJ. , et al. Clopidogrel treatment and the incidence and severity of community acquired pneumonia in a cohort study and meta-analysis of antiplatelet therapy in pneumonia and critical illness. J Thromb Thrombolysis 2013; 35 (02) 147-154
    CrossrefPubMedSearch in Google Scholar
  • 104 Storey RF, James SK, Siegbahn A. , et al. Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study. Platelets 2014; 25 (07) 517-525
    CrossrefPubMedSearch in Google Scholar
  • 105 Sexton TR, Zhang G, Macaulay TE. , et al. Ticagrelor reduces thromboinflammatory markers in patients with pneumonia. JACC Basic Transl Sci 2018; 3 (04) 435-449
    PubMedSearch in Google Scholar
  • 106 Aungraheeta R, Conibear A, Butler M. , et al. Inverse agonism at the P2Y12 receptor and ENT1 transporter blockade contribute to platelet inhibition by ticagrelor. Blood 2016; 128 (23) 2717-2728
    PubMedSearch in Google Scholar
  • 107 Lancellotti P, Musumeci L, Jacques N. , et al. Antibacterial activity of ticagrelor in conventional antiplatelet dosages against antibiotic-resistant Gram-positive bacteria. JAMA Cardiol 2019; 4 (06) 596-599
    CrossrefPubMedSearch in Google Scholar
  • 108 Itkonen MK, Tornio A, Lapatto-Reiniluoto O. , et al. Clopidogrel increases dasabuvir exposure with or without ritonavir, and ritonavir inhibits the bioactivation of clopidogrel. Clin Pharmacol Ther 2019; 105 (01) 219-228
    CrossrefPubMedSearch in Google Scholar
  • 109 Marsousi N, Daali Y, Fontana P. , et al. Impact of boosted antiretroviral therapy on the pharmacokinetics and efficacy of clopidogrel and prasugrel active metabolites. Clin Pharmacokinet 2018; 57 (10) 1347-1354
    CrossrefPubMedSearch in Google Scholar
  • 110 Terpos E, Ntanasis-Stathopoulos I, Elalamy I. , et al. Hematological findings and complications of COVID-19. Am J Hematol 2020
    PubMedSearch in Google Scholar
  • 111 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
  • 112 Gresele P, Momi S, Falcinelli E. Anti-platelet therapy: phosphodiesterase inhibitors. Br J Clin Pharmacol 2011; 72 (04) 634-646
    CrossrefPubMedSearch in Google Scholar
  • 113 Tonew E, Indulen MK, Dzeguze DR. Antiviral action of dipyridamole and its derivatives against influenza virus A. Acta Virol 1982; 26 (03) 125-129
    PubMedSearch in Google Scholar
  • 114 Li Z, Li X, Huang Y-Y. , et al. FEP-based screening prompts drug repositioning against COVID-19. bioRxiv 2020 : 2020.03.23.004580
    PubMed
  • 115 Liu X, Li Z, Liu S. , et al. Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19. Acta Pharm Sin B 2020;
    CrossrefPubMedSearch in Google Scholar
  • 116 Baker NC, Lipinski MJ, Lhermusier T, Waksman R. Overview of the 2014 Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee meeting about vorapaxar. Circulation 2014; 130 (15) 1287-1294
    CrossrefPubMedSearch in Google Scholar
  • 117 Morrow DA, Braunwald E, Bonaca MP. , et al; TRA 2P–TIMI 50 Steering Committee and Investigators. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 2012; 366 (15) 1404-1413
    CrossrefPubMedSearch in Google Scholar
  • 118 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
  • 119 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 . Doi: 10.1111/jth.14850
    PubMedSearch in Google Scholar
  • 120 Rezaie AR, Giri H. Antithrombin: an anticoagulant, anti-inflammatory and antibacterial serpin. J Thromb Haemost 2020; 18 (03) 528-533
    CrossrefPubMedSearch in Google Scholar
  • 121 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; /j/cclm.ahead-of-print/cclm-2020-0188/cclm-2020-0188.xml
    CrossrefPubMedSearch in Google Scholar
  • 122 Hofstra JJ, Vlaar AP, Cornet AD. , et al. Nebulized anticoagulants limit pulmonary coagulopathy, but not inflammation, in a model of experimental lung injury. J Aerosol Med Pulm Drug Deliv 2010; 23 (02) 105-111
    CrossrefPubMedSearch in Google Scholar
  • 123 Cornet AD, Hofstra JJ, Vlaar AP. , et al. Nebulized anticoagulants limit coagulopathy but not inflammation in pseudomonas aeruginosa-induced pneumonia in rats. Shock 2011; 36 (04) 417-423
    CrossrefPubMedSearch in Google Scholar
  • 124 Uchiba M, Okajima K, Murakami K. Effects of various doses of antithrombin III on endotoxin-induced endothelial cell injury and coagulation abnormalities in rats. Thromb Res 1998; 89 (05) 233-241
    CrossrefPubMedSearch in Google Scholar
  • 125 Warren BL, Eid A, Singer P. , et al; KyberSept Trial Study Group. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001; 286 (15) 1869-1878
    CrossrefPubMedSearch in Google Scholar
  • 126 Allingstrup M, Wetterslev J, Ravn FB, Møller AM, Afshari A. Antithrombin III for critically ill patients: a systematic review with meta-analysis and trial sequential analysis. Intensive Care Med 2016; 42 (04) 505-520
    CrossrefPubMedSearch in Google Scholar
  • 127 Ito T, Thachil J, Asakura H, Levy JH, Iba T. Thrombomodulin in disseminated intravascular coagulation and other critical conditions-a multi-faceted anticoagulant protein with therapeutic potential. Crit Care 2019; 23 (01) 280
    CrossrefPubMedSearch in Google Scholar
  • 128 Vincent JL, Francois B, Zabolotskikh I. , et al; SCARLET Trial Group. Effect of a recombinant human soluble thrombomodulin on mortality in patients with sepsis-associated coagulopathy: the SCARLET randomized clinical trial. JAMA 2019; 321 (20) 1993-2002
    CrossrefPubMedSearch in Google Scholar
  • 129 Valeriani E, Squizzato A, Gallo A. , et al. Efficacy and safety of recombinant human soluble thrombomodulin in patients with sepsis-associated coagulopathy: a systematic review and meta-analysis. J Thromb Haemost 2020 . Doi: 10.1111/jth.14812
    PubMedSearch in Google Scholar
  • 130 Griffin JH, Zlokovic BV, Mosnier LO. Activated protein C: biased for translation. Blood 2015; 125 (19) 2898-2907
    CrossrefPubMedSearch in Google Scholar
  • 131 Ranieri VM, Thompson BT, Barie PS. , et al; PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 2012; 366 (22) 2055-2064
    CrossrefPubMedSearch in Google Scholar
  • 132 Gentry CA, Gross KB, Sud B, Drevets DA. Adverse outcomes associated with the use of drotrecogin alfa (activated) in patients with severe sepsis and baseline bleeding precautions. Crit Care Med 2009; 37 (01) 19-25
    CrossrefPubMedSearch in Google Scholar
  • 133 Cornet AD, Hofstra JJ, Vlaar AP. , et al. Activated protein C attenuates pulmonary coagulopathy in patients with acute respiratory distress syndrome. J Thromb Haemost 2013; 11 (05) 894-901
    CrossrefPubMedSearch in Google Scholar
  • 134 Cornet AD, Groeneveld AB, Hofstra JJ. , et al. Recombinant human activated protein C in the treatment of acute respiratory distress syndrome: a randomized clinical trial. PLoS One 2014; 9 (03) e90983
    CrossrefPubMedSearch in Google Scholar
  • 135 Al-Abdallat MM, Payne DC, Alqasrawi S. , et al; Jordan MERS-CoV Investigation Team. Hospital-associated outbreak of Middle East respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description. Clin Infect Dis 2014; 59 (09) 1225-1233
    CrossrefPubMedSearch in Google Scholar
  • 136 Lupu F, Keshari R, Silasi R. , et al. Blocking activated factor XII with a monoclonal antibody prevents organ failure and saves baboons challenged with heat-inactivated S. aureus. Res Pr Thromb Haemost 2019; 3 (Suppl. 01) 127-128
    PubMedSearch in Google Scholar
  • 137 Silasi R, Keshari RS, Lupu C. , et al. Inhibition of contact-mediated activation of factor XI protects baboons against S aureus-induced organ damage and death. Blood Adv 2019; 3 (04) 658-669
    CrossrefPubMedSearch in Google Scholar
  • 138 Jansen PM, Pixley RA, Brouwer M. , et al. Inhibition of factor XII in septic baboons attenuates the activation of complement and fibrinolytic systems and reduces the release of interleukin-6 and neutrophil elastase. Blood 1996; 87 (06) 2337-2344
    CrossrefPubMedSearch in Google Scholar
  • 139 Pixley RA, De La Cadena R, Page JD. , et al. The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal anti-factor XII antibody to block contact activation in baboons. J Clin Invest 1993; 91 (01) 61-68
    CrossrefPubMedSearch in Google Scholar
  • 140 Tucker EI, Verbout NG, Leung PY. , et al. Inhibition of factor XI activation attenuates inflammation and coagulopathy while improving the survival of mouse polymicrobial sepsis. Blood 2012; 119 (20) 4762-4768
    CrossrefPubMedSearch in Google Scholar
  • 141 Luo D, Szaba FM, Kummer LW. , et al. Factor XI-deficient mice display reduced inflammation, coagulopathy, and bacterial growth during listeriosis. Infect Immun 2012; 80 (01) 91-99
    CrossrefPubMedSearch in Google Scholar
  • 142 Shatzel JJ, DeLoughery EP, Lorentz CU. , et al. The contact activation system as a potential therapeutic target in patients with COVID-19. Res Pract Thromb Haemost 2020 . Doi: 10.1002/rth2.12349
    PubMedSearch in Google Scholar
  • 143 Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. JAMA 2020 . Doi: 10.1001/jama.2020.6019
    PubMedSearch in Google Scholar
  • 144 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; e200994
    PubMedSearch in Google Scholar
  • 145 Stockman LJ, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS Med 2006; 3 (09) e343
    CrossrefPubMedSearch in Google Scholar
  • 146 Arabi YM, Mandourah Y, Al-Hameed F. , et al; Saudi Critical Care Trial Group. Corticosteroid therapy for critically ill patients with middle east respiratory syndrome. Am J Respir Crit Care Med 2018; 197 (06) 757-767
    CrossrefPubMedSearch in Google Scholar
  • 147 Lansbury L, Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Lim WS. Corticosteroids as adjunctive therapy in the treatment of influenza. Cochrane Database Syst Rev 2019; 2: CD010406
    PubMedSearch in Google Scholar
  • 148 Lee JJ, Pope JE. A meta-analysis of the risk of venous thromboembolism in inflammatory rheumatic diseases. Arthritis Res Ther 2014; 16 (05) 435
    CrossrefPubMedSearch in Google Scholar
  • 149 Zöller B, Li X, Sundquist J, Sundquist K. Risk of pulmonary embolism in patients with autoimmune disorders: a nationwide follow-up study from Sweden. Lancet 2012; 379 (9812): 244-249
    CrossrefPubMedSearch in Google Scholar
  • 150 Johannesdottir SA, Horváth-Puhó E, Dekkers OM. , et al. Use of glucocorticoids and risk of venous thromboembolism: a nationwide population-based case-control study. JAMA Intern Med 2013; 173 (09) 743-752
    CrossrefPubMedSearch in Google Scholar
  • 151 van Zaane B, Nur E, Squizzato A. , et al. Systematic review on the effect of glucocorticoid use on procoagulant, anti-coagulant and fibrinolytic factors. J Thromb Haemost 2010; 8 (11) 2483-2493
    CrossrefPubMedSearch in Google Scholar
  • 152 Huerta C, Johansson S, Wallander MA, García Rodríguez LA. Risk factors and short-term mortality of venous thromboembolism diagnosed in the primary care setting in the United Kingdom. Arch Intern Med 2007; 167 (09) 935-943
    CrossrefPubMedSearch in Google Scholar
  • 153 Khilnani GC, Hadda V. Corticosteroids and ARDS: a review of treatment and prevention evidence. Lung India 2011; 28 (02) 114-119
    CrossrefPubMedSearch in Google Scholar
  • 154 Espinola RG, Pierangeli SS, Gharavi AE, Harris EN. Hydroxychloroquine reverses platelet activation induced by human IgG antiphospholipid antibodies. Thromb Haemost 2002; 87 (03) 518-522
    Thieme ConnectPubMedSearch in Google Scholar
  • 155 Petri M. Use of hydroxychloroquine to prevent thrombosis in systemic lupus erythematosus and in antiphospholipid antibody-positive patients. Curr Rheumatol Rep 2011; 13 (01) 77-80
    CrossrefPubMedSearch in Google Scholar
  • 156 Schreiber K, Sciascia S, de Groot PG. , et al. Antiphospholipid syndrome. Nat Rev Dis Primers 2018; 4: 18005
    CrossrefPubMedSearch in Google Scholar
  • 157 Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 2010; 69 (01) 20-28
    CrossrefPubMedSearch in Google Scholar
  • 158 Edwards MH, Pierangeli S, Liu X, Barker JH, Anderson G, Harris EN. Hydroxychloroquine reverses thrombogenic properties of antiphospholipid antibodies in mice. Circulation 1997; 96 (12) 4380-4384
    CrossrefPubMedSearch in Google Scholar
  • 159 Schreiber K, Breen K, Parmar K, Rand JH, Wu XX, Hunt BJ. The effect of hydroxychloroquine on haemostasis, complement, inflammation and angiogenesis in patients with antiphospholipid antibodies. Rheumatology (Oxford) 2018; 57 (01) 120-124
    CrossrefPubMedSearch in Google Scholar
  • 160 Johansson E, Forsberg K, Johnsson H. Clinical and experimental evaluation of the thromboprophylactic effect of hydroxychloroquine sulfate after total hip replacement. Haemostasis 1981; 10 (02) 89-96
    PubMedSearch in Google Scholar
  • 161 Loudon JR. Hydroxychloroquine and postoperative thromboembolism after total hip replacement. Am J Med 1988; 85 (4A): 57-61
    CrossrefPubMedSearch in Google Scholar
  • 162 Bessière F, Roccia H, Delinière A. , et al. Assessment of QT intervals in a case series of patients with coronavirus disease 2019 (COVID-19) infection treated with hydroxychloroquine alone or in combination with azithromycin in an intensive care unit. JAMA Cardiol 2020; e201787
    PubMedSearch in Google Scholar
  • 163 Grundy SM, Stone NJ, Bailey AL. , et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019; 73 (24) 3168-3209
    CrossrefPubMedSearch in Google Scholar
  • 164 Oesterle A, Laufs U, Liao JK. Pleiotropic effects of statins on the cardiovascular system. Circ Res 2017; 120 (01) 229-243
    CrossrefPubMedSearch in Google Scholar
  • 165 Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395 (10229): 1033-1034
    CrossrefPubMedSearch in Google Scholar
  • 166 Dashti-Khavidaki S, Khalili H. Considerations for statin therapy in patients with COVID-19. Pharmacotherapy 2020; 40 (05) 484-486
    CrossrefPubMedSearch in Google Scholar
  • 167 Kong F, Ye B, Lin L, Cai X, Huang W, Huang Z. Atorvastatin suppresses NLRP3 inflammasome activation via TLR4/MyD88/NF-κB signaling in PMA-stimulated THP-1 monocytes. Biomed Pharmacother 2016; 82: 167-172
    CrossrefPubMedSearch in Google Scholar
  • 168 Vandermeer ML, Thomas AR, Kamimoto L. , et al. Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: a multistate study. J Infect Dis 2012; 205 (01) 13-19
    CrossrefPubMedSearch in Google Scholar
  • 169 Yuan S. Statins may decrease the fatality rate of Middle East respiratory syndrome infection. MBio 2015; 6 (04) e01120
    PubMedSearch in Google Scholar
  • 170 DeDiego ML, Nieto-Torres JL, Regla-Nava JA. , et al. Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol 2014; 88 (02) 913-924
    CrossrefPubMedSearch in Google Scholar
  • 171 Violi F, Calvieri C, Ferro D, Pignatelli P. Statins as antithrombotic drugs. Circulation 2013; 127 (02) 251-257
    CrossrefPubMedSearch in Google Scholar
  • 172 Glynn RJ, Danielson E, Fonseca FA. , et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med 2009; 360 (18) 1851-1861
    CrossrefPubMedSearch in Google Scholar
  • 173 Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA 1998; 279 (20) 1643-1650
    CrossrefPubMedSearch in Google Scholar
  • 174 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
  • 175 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; S1931-5244(20)30070-0
    PubMedSearch in Google Scholar
  • 176 Stebbing J, Phelan A, Griffin I. , et al. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis 2020; 20 (04) 400-402
    CrossrefPubMedSearch in Google Scholar
  • 177 Taylor PC, Weinblatt ME, Burmester GR. , et al. Cardiovascular safety during treatment with baricitinib in rheumatoid arthritis. Arthritis Rheumatol 2019; 71 (07) 1042-1055
    PubMedSearch in Google Scholar
  • 178 National Institutes of Health Coronavirus Disease. 2019 (COVID-19) Treatment Guidelines. Available at: https://www.covid19treatmentguidelines.nih.gov/ . Accessed April 22, 2020
    PubMed
  • 179 Genentech's arthritis drug tocilizumab shows promise in Covid-19 trial. April 29, 2020. Available at: https://www.clinicaltrialsarena.com/news/french-early-trial-tocilizumab-covid-19/ . Accessed May 14, 2020
    PubMed
  • 180 Cummings MJ, Baldwin MR, Abrams D et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet 2020; 395 (10239): 1763-1770
    CrossrefPubMedSearch in Google Scholar
  • 181 Richardson S, Hirsch JS, Narasimhan M. , et al; and the Northwell COVID-19 Research Consortium. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. JAMA 2020; e206775
    PubMedSearch in Google Scholar
  • 182 Li J, Li Y, Yang B. , et al. Low-molecular-weight heparin treatment for acute lung injury/acute respiratory distress syndrome: a meta-analysis of randomized controlled trials. Int J Clin Exp Med 2018; 11 (02) 414-422
    PubMedSearch in Google Scholar
  • 183 Ghezzi S, Cooper L, Rubio A. , et al. Heparin prevents Zika virus induced-cytopathic effects in human neural progenitor cells. Antiviral Res 2017; 140: 13-17
    CrossrefPubMedSearch in Google Scholar
  • 184 Vicenzi E, Canducci F, Pinna D. , et al. Coronaviridae and SARS-associated coronavirus strain HSR1. Emerg Infect Dis 2004; 10 (03) 413-418
    CrossrefPubMedSearch in Google Scholar
  • 185 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
    PubMedSearch in Google Scholar
  • 186 Mycroft-West C, Su D, Elli S, et al. The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding. bioRxiv 2020: 2020.02.29.971093
    PubMed
  • 187 Paranjpe I, Fuster V, Lala A. , et al. Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19. J Am Coll Cardiol 2020; S0735-1097(20)35218-9
    PubMedSearch in Google Scholar
  • 188 Lindhoff-Last E, Betz C, Bauersachs R. Use of a low-molecular-weight heparinoid (danaparoid sodium) for continuous renal replacement therapy in intensive care patients. Clin Appl Thromb Hemost 2001; 7 (04) 300-304
    CrossrefPubMedSearch in Google Scholar
  • 189 Chang JC. Acute respiratory distress syndrome as an organ phenotype of vascular microthrombotic disease: based on hemostatic theory and endothelial molecular pathogenesis. Clin Appl Thromb Hemost 2019; 25: 1076029619887437
    CrossrefPubMedSearch in Google Scholar
  • 190 Liu X, Li Z, Liu S. , et al. Therapeutic effects of dipyridamole on COVID-19 patients with coagulation dysfunction. medRxiv 2020
    PubMed
  • 191 Sarangi PP, Lee HW, Kim M. Activated protein C action in inflammation. Br J Haematol 2010; 148 (06) 817-833
    CrossrefPubMedSearch in Google Scholar
  • 192 Lu X, Chen T, Wang Wang. , et al. Adjuvant corticosteroid therapy for critically ill patients with COVID-19. medRxiv 2020 : 2020.04.07.20056390
    PubMedSearch in Google Scholar
  • 193 Zhang Y, Xiao M, Zhang S. , et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N Engl J Med 2020; 382 (17) e38
    CrossrefPubMedSearch in Google Scholar
  • 194 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
    CrossrefPubMedSearch in Google Scholar