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

Author:

Madhavan Mahesh V.12,Bikdeli Behnood132,Gupta Aakriti132,Jimenez David45,Burton John R.1,Der Nigoghossian Caroline1,Chuich Taylor1,Nouri Shayan Nabavi1,Dreyfus Isaac1,Driggin Elissa1,Sethi Sanjum1,Sehgal Kartik67,Chatterjee Saurav8,Ageno Walter9,Madjid Mohammad10,Guo Yutao1112ORCID,Tang Liang V.13,Hu Yu13,Bertoletti Laurent14ORCID,Giri Jay151617,Cushman Mary18,Quéré Isabelle19,Dimakakos Evangelos P.20,Gibson C. Michael67,Lippi Giuseppe21,Favaloro Emmanuel J.2223,Fareed Jawed24,Tafur Alfonso J.2526,Francese Dominic P.2,Batra Jaya1,Falanga Anna27,Clerkin Kevin J.1,Uriel Nir1,Kirtane Ajay12,McLintock Claire28,Hunt Beverley J.29,Spyropoulos Alex C.30,Barnes Geoffrey D.3132,Eikelboom John W.33,Weinberg Ido634,Schulman Sam353637,Carrier Marc38,Piazza Gregory639,Beckman Joshua A.40,Leon Martin B.12,Stone Gregg W.241,Rosenkranz Stephan42,Goldhaber Samuel Z.639,Parikh Sahil A.12,Monreal Manuel43,Krumholz Harlan M.34445,Konstantinides Stavros V.46ORCID,Weitz Jeffrey I.3637,Lip Gregory Y. H.1247ORCID,

Affiliation:

1. New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States

2. Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

3. Center for Outcomes Research and Evaluation (CORE), Yale School of Medicine, New Haven, Connecticut, United States

4. Respiratory Department, Hospital Ramón y Cajal, Madrid, Spain

5. Medicine Department, Universidad de Alcalá (IRYCIS), CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain

6. Harvard Medical School, Boston, Massachusetts, United States

7. Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States

8. North Shore and Long Island Jewish University Hospitals, Queens, New York, United States

9. Department of Medicine and Surgery, University of Insubria, Varese, Italy

10. McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, United States

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

13. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

14. Department of “Médecine Vasculaire et Thérapeutique,” CIC 1408, INNOVTE, CHU de St-Etienne and INSERM UMR1059, Université Jean-Monnet, Saint-Etienne, France

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

18. Larner College of Medicine, University of Vermont, Burlington, Vermont, United States

19. Department of Vascular Medicine, University of Montpellier, Montpellier CHU, InnoVTE F-CRIN Network, Montpellier, France

20. Oncology Unit GPP, Sotiria General Hospital, Athens School of Medicine, Athens, Greece

21. Laboratory of Clinical Chemistry and Hematology, University Hospital of Verona, Verona, Italy

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

24. Loyola University Medical Center, Chicago, Illinois, United States

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

27. Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, University of Milan Bicocca, Bergamo, Italy

28. Auckland City Hospital, Auckland, New Zealand

29. St Thomas' Hospital, London, United Kingdom

30. The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, New York, United States

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

33. Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada

34. Massachusetts General Hospital, Boston, Massachusetts, United States

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

38. The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

39. Brigham and Women's Hospital, Boston, Massachusetts, United States

40. Vanderbilt University School of Medicine, Nashville, Tennessee, United States

41. The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States

42. Department of Cardiology, Cologne Cardiovascular Research Center (CCRC), Heart Center at the University of Cologne, University of Cologne, Cologne, Germany

43. Department of Internal Medicine, Hospital Universitari Germans Trials I Pujol, Universidad Católica de Murcia, Barcelona, Spain

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

46. Center for Thrombosis and Hemostasis, Johannes Gutenberg University of Mainz, Mainz, Germany

47. Department of Clinical Medicine, Aalborg Thrombosis Research Unit, Aalborg University, Aalborg, Denmark

Abstract

AbstractCoronavirus 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.

Publisher

Georg Thieme Verlag KG

Subject

Hematology

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