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

Behnood Bikdeli; Mahesh V. Madhavan; Aakriti Gupta; David Jimenez; John R. Burton; Caroline Der Nigoghossian; Taylor Chuich; Shayan Nabavi Nouri; Isaac Dreyfus; Elissa Driggin; Sanjum Sethi; Kartik Sehgal; Saurav Chatterjee; Walter Ageno; Mohammad Madjid; Yutao Guo; Liang V. Tang; Yu Hu; Laurent Bertoletti; Jay Giri; Mary Cushman; Isabelle Quéré; Evangelos P. Dimakakos; C. Michael Gibson; Giuseppe Lippi; Emmanuel J. Favaloro; Jawed Fareed; Alfonso J. Tafur; Dominic P. Francese; Jaya Batra; Anna Falanga; Kevin J. Clerkin; Nir Uriel; Ajay Kirtane; Claire McLintock; Beverley J. Hunt; Alex C. Spyropoulos; Geoffrey D. Barnes; John W. Eikelboom; Ido Weinberg; Sam Schulman; Marc Carrier; Gregory Piazza; Joshua A. Beckman; Martin B. Leon; Gregg W. Stone; Stephan Rosenkranz; Samuel Z. Goldhaber; Sahil A. Parikh; Manuel Monreal; Harlan M. Krumholz; Stavros V. Konstantinides; Jeffrey I. Weitz; Gregory Y. H. Lip; The Global COVID-19 Thrombosis Collaborative Group

doi:10.1055/s-0040-1713152

Thrombosis and Haemostasis, Inhaltsverzeichnis

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^*

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

²Center for Outcomes Research and Evaluation (CORE), Yale School of Medicine, New Haven, Connecticut, United States

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

Mahesh V. Madhavan‡^*

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

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

Aakriti Gupta

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

²Center for Outcomes Research and Evaluation (CORE), Yale School of Medicine, New Haven, Connecticut, United States

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

David Jimenez

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

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

,

John R. Burton

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

,

Caroline Der Nigoghossian

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

,

Taylor Chuich

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

,

Shayan Nabavi Nouri

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

,

Isaac Dreyfus

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

,

Elissa Driggin

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

,

Sanjum Sethi

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

,

Kartik Sehgal

⁶Harvard Medical School, Boston, Massachusetts, United States

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

,

Saurav Chatterjee

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

,

Walter Ageno

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

,

Mohammad Madjid

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

,

Yutao Guo

¹¹Department of Cardiology, Chinese PLA General Hospital, Beijing, China

¹²Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom

,

Liang V. Tang

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

,

Yu Hu

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

,

Laurent Bertoletti

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

,

Jay Giri

¹⁵Cardiovascular Division, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States

¹⁶Penn Cardiovascular Outcomes, Quality, and Evaluative Research Center, Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania, United States

¹⁷Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, United States

,

Mary Cushman

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

,

Isabelle Quéré

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

,

Evangelos P. Dimakakos

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

,

C. Michael Gibson

⁶Harvard Medical School, Boston, Massachusetts, United States

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

,

Giuseppe Lippi

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

,

Emmanuel J. Favaloro

²²Laboratory Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia

²³Sydney Centres for Thrombosis and Haemostasis, Westmead, NSW, Australia

,

Jawed Fareed

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

,

Alfonso J. Tafur

²⁵Pritzker School of Medicine at the University of Chicago, Chicago, Illinois, United States

²⁶Division of Vascular Medicine, Department of Medicine, NorthShore University HealthSystem, Skokie, Illinois, United States

,

Dominic P. Francese

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

Jaya Batra

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

,

Anna Falanga

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

,

Kevin J. Clerkin

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

,

Nir Uriel

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

,

Ajay Kirtane

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

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

Claire McLintock

²⁸Auckland City Hospital, Auckland, New Zealand

,

Beverley J. Hunt

²⁹St Thomas' Hospital, London, United Kingdom

,

Alex C. Spyropoulos

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

,

Geoffrey D. Barnes

³¹Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, Michigan, United States

³²Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, United States

,

John W. Eikelboom

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

,

Ido Weinberg

⁶Harvard Medical School, Boston, Massachusetts, United States

³⁴Massachusetts General Hospital, Boston, Massachusetts, United States

,

Sam Schulman

³⁵Department of Obstetrics and Gynecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia

³⁶McMaster University, Hamilton, Ontario, Canada

³⁷Thrombosis & Atherosclerosis Research Institute, Hamilton, Ontario, Canada

,

Marc Carrier

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

,

Gregory Piazza

⁶Harvard Medical School, Boston, Massachusetts, United States

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

,

Joshua A. Beckman

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

,

Martin B. Leon

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

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

Gregg W. Stone

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

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

,

Stephan Rosenkranz

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

,

Samuel Z. Goldhaber

⁶Harvard Medical School, Boston, Massachusetts, United States

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

,

Sahil A. Parikh

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

³Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, United States

,

Manuel Monreal

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

,

Harlan M. Krumholz

²Center for Outcomes Research and Evaluation (CORE), Yale School of Medicine, New Haven, Connecticut, United States

⁴⁴Department of Health Policy and Administration, Yale School of Public Health, New Haven, Connecticut, United States

⁴⁵Section of Cardiovascular Medicine, Department of Internal Medicie, Yale School of Medicine, New Haven, Connecticut, United States

,

Stavros V. Konstantinides

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

,

Jeffrey I. Weitz

³⁶McMaster University, Hamilton, Ontario, Canada

³⁷Thrombosis & Atherosclerosis Research Institute, Hamilton, Ontario, Canada

,

Gregory Y. H. Lip

¹²Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom

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

,

The Global COVID-19 Thrombosis Collaborative Group

› Institutsangaben

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

Volltext

Referenzen

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