Thromb Haemost
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
,
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
,
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
,
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
,
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)

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.

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


Supplementary Material