The Present and Future
JACC State-of-the-Art Review
COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review

https://doi.org/10.1016/j.jacc.2020.04.031Get rights and content
Under an Elsevier user license
open archive

Highlights

  • COVID-19 may predispose patients to arterial and venous thrombosis.

  • Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19. The optimal preventive strategy warrants further investigation.

  • Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.

  • The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.

Abstract

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.

Key Words

anticoagulant
antiplatelet
antithrombotic therapy
COVID-19
SARS-CoV-2
thrombosis

Abbreviations and Acronyms

ACS
acute coronary syndrome
COVID-19
coronavirus disease-2019
DIC
disseminated intravascular coagulation
DOAC
direct oral anticoagulant
DVT
deep vein thrombosis
ECMO
extracorporeal membrane oxygenation
LMWH
low-molecular-weight heparin
PE
pulmonary embolism
SARS-CoV-2
severe acute respiratory syndrome-coronavirus-2
STEMI
ST-segment elevation myocardial infarction
UFH
unfractionated heparin
VKA
vitamin K antagonist
VTE
venous thromboembolism

Cited by (0)

This work was endorsed by the International Society on Thrombosis and Haemostasis, North American Thrombosis Forum, European Society of Vascular Medicine, and International Union of Angiology; and supported by the European Society of Cardiology Working Group on the Pulmonary Circulation and Right Ventricular Function (to Drs. Rosenkranz and Konstantinides). Dr. Madhavan was supported by a grant from the National Institutes of Health/National Heart, Lung, and Blood Institute to Columbia University Irving Medical Center (T32 HL007854). Dr. Bikdeli has served as a consulting expert, on behalf of the plaintiff, for litigation related to a specific type of inferior vena cava filters. Dr. Jimenez has served as an advisor or consultant for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Leo Pharma, Pfizer, ROVI and Sanofi; has served as a speaker or a member of a Speakers Bureau for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Leo Pharma, ROVI, and Sanofi; and has received grants for clinical research from Daiichi-Sankyo, Sanofi, and ROVI. Dr. Ageno has received a research grant from Bayer; and has recevied honoraria for participation in Advisory Boards from Boehringer Ingelheim, Bayer Pharmaceuticals, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, Aspen, Sanofi, Portola, Leo Pharma, and Janssen. Dr. Giri has served on the Advisory Board for AstraZeneca; has served on the Trial Steering Committee for Inari Medical; has received institutional research grant support from Recor Medical and St. Jude Medical; and has received personal fees for trial adjudication from the New England Research Institute. Dr. Quéré has received lecture fees from Pfizer, Bayer Pharmaceuticals, Aspen, and Leo Pharma. Dr. Dimakakos has received consulting fees from Sanofi and Leo Pharma. Dr. Caprini has served on the steering committee for Janssen R&D; has served on the bleeding Advisory Board for Pfizer; has served on the Advisory Board for Bristol-Myers Squibb and Alexion Pharmaceuticals; has served as a consultant for Recovery Force; and has received honoraria from Sanofi. Dr. Tafur has served as a consultant for Recovery Force; has conducted research for Janssen, Bristol-Myers Squibb, Doasense, and Idorsia; and has received educational grant support from Janssen. Dr. Falanga has received speaker honoraria from Bayer, Pfizer, and Sanofi. Dr. Hunt has served as chair of the steering group of World Thrombosis Day and Medical Director of Thrombosis UK, 2 not-for-profit organizations from which she takes no fees. Dr. Spyropoulos has served as a consultant for Boehringer Ingelheim, Janssen, Bristol-Myers Squibb, Bayer, Portola, and the ATLAS Group; and has received research grant support from Boehringer Ingelheim and Janssen. Dr. Barnes has served as a consultant for Pfizer/Bristol-Myers Squibb, Janssen, Portola, and AMAG Pharmaceuticals. Dr. Barnes has served as a consultant for Pfizer/Bristol-Myers Squibb, Janssen, Portola, and AMAG Pharmaceuticals; and has received grant funding from Pfizer/Bristol-Myers Squibb, and Blue Cross Blue Shield of Michigan. Dr. Eikelboom has received consulting fees and/or honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Pfizer, Janssen, Sanofi, and Servier; and has received grants and/or in-kind support from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Janssen, and Sanofi. Dr. Weinberg has received consulting fees from Magneto Thrombectomy Solutions. Dr. Schulman has received research grant support from Octapharma and Boehringer Ingelheim; and has received honoraria from Alnylam, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, and Sanofi. Dr. Beckman has served on the Advisory Board for Amgen, AstraZeneca, GlaxoSmithKline, and Janssen; has served on the Data Safety Monitoring Board for Bayer and Novartis; has received consulting fees from JanOne; and has received personal fees for trial adjudication from Sanofi. Dr. Carrier has received research funding from Bristol-Myers Squibb, Leo Pharma, and Pfizer; and has received consulting honoraria from Bristol-Myers Squibb, Bayer, Pfizer, Leo Pharma, Servier, and Sanofi. Dr. Piazza has received research grant support from EKOS/BTG International, Bristol-Myers Squibb, Daiichi-Sankyo, Bayer, Portola, and Janssen; and has received consulting fees from Pfizer and Thrombolex. Dr. Steg has received research grants from Amarin, Bayer, Sanofi, and Servier; has served on the Steering Committee, Data Safety Monitoring Board, or Clinical Endpoint Committee for clinical trials for Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Idorsia, Novartis, Pfizer, Sanofi, and Servier; and has received speaker or consulting fees from Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Idorsia, Novartis, Pfizer, Sanofi, and Servier. Dr. Stone has received speaker or other honoraria from Cook, Terumo, QOOL Therapeutics, and Orchestra Biomed; has served as a consultant to Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, V-Wave, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious, Reva, and Matrizyme; and has equity/options from Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, MedFocus family of funds, and Valfix. Dr. Rosenkranz has received consulting and/or lecture fees from Abbott, Acceleron, Actelion, AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, and United Therapeutics; and has received institutional research grants from Actelion, AstraZeneca, Bayer, Novartis, Deutsche Forschungsgemeinschaft, Else-Bundesministerium für Bildung und Forschung, and Kröner-Fresenius-Stiftung. Dr. Goldhaber has received research support from Bayer, Boehringer Ingelheim, Bristol-Myers-Squibb, BTG EKOS, Daiichi-Sankyo, Janssen, the U.S. National Heart, Blood, and Lung Institute, and the Thrombosis Research Institute; and has received consulting fees from Bayer and Boehringer Ingelheim. Dr. Parikh has received institutional grants/research support from Abbott Vascular, Shockwave Medical, TriReme Medical, and Surmodics; and has received consulting fees from Terumo and Abiomed; has participated on Advisory Boards for Abbott, Boston Scientific, CSI, Janssen, Medtronic, and Philips; and has served on the Data Safety and Monitoring Board for Silk Road Medical. Dr. Monreal has served as an advisor or consultant for Sanofi, Leo Pharma, and Daiichi-Sankyo; and has received a nonrestricted educational grant by Sanofi and Bayer to sponsor the RIETE registry. Dr. Krumholz has worked under contract with the Centers for Medicare & Medicaid Services to support quality measurement programs; has received institutional research grant support from Medtronic and the U.S. Food and Drug Administration, Johnson & Johnson, and Shenzhen Center for Health Information; has served as a consultant for the National Center for Cardiovascular Diseases in Beijing; has received consulting fees from Arnold & Porter law firm (Sanofi clopidogrel litigation), Ben C. Martin law firm (Cook Celect IVC filter litigation), and Siegfried and Jensen law firm (Vioxx litigation); has served as Cardiac Scientific Advisory Board chair for UnitedHealth; has served as a member of the IBM Watson Health Life Sciences Board; has served on the Advisory Board for Element Science and Facebook; has served on the Physician Advisory Board for Aetna; and is the cofounder of HugoHealth and Refactor Health. Dr. Konstantinides has received research grant support from Bayer AG, Boehringer Ingelheim, Actelion/Janssen; has received educational grant support from Biocompatibles Group UK/Boston Scientific, and Daiichi-Sankyo; and has received lecture fees from Bayer AG, Pfizer/Bristol-Myers Squibb, and Merck Sharp and Dohme. Dr. Weitz has served as a consultant to and received honoraria from Bayer, Janssen, Johnson & Johnson, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, Novartis, Daiichi-Sankyo, Merck, Servier, Anthos, Ionis, and PhaseBio. Dr. Lip has served as a consultant for Bayer/Janssen, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi-Sankyo; and has served as a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Thomas M. Maddox, MD, MSc, served as Guest Editor-in-Chief for this paper.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.

Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.

Drs. Bikdeli and Madhavan contributed equally to this work.