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Review
. 2020 Jul;120(7):1004-1024.
doi: 10.1055/s-0040-1713152. Epub 2020 May 30.

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

Behnood Bikdeli  1   2   3 , Mahesh V Madhavan #  1   3 , Aakriti Gupta  1   2   3 , David Jimenez  4   5 , John R Burton  1 , Caroline Der Nigoghossian  1 , Taylor Chuich  1 , Shayan Nabavi Nouri  1 , Isaac Dreyfus  1 , Elissa Driggin  1 , Sanjum Sethi  1 , Kartik Sehgal  6   7 , Saurav Chatterjee  8 , Walter Ageno  9 , Mohammad Madjid  10 , Yutao Guo  11   12 , Liang V Tang  13 , Yu Hu  13 , Laurent Bertoletti  14 , Jay Giri  15   16   17 , Mary Cushman  18 , Isabelle Quéré  19 , Evangelos P Dimakakos  20 , C Michael Gibson  6   7 , Giuseppe Lippi  21 , Emmanuel J Favaloro  22   23 , Jawed Fareed  24 , Alfonso J Tafur  25   26 , Dominic P Francese  3 , Jaya Batra  1 , Anna Falanga  27 , Kevin J Clerkin  1 , Nir Uriel  1 , Ajay Kirtane  1   3 , Claire McLintock  28 , Beverley J Hunt  29 , Alex C Spyropoulos  30 , Geoffrey D Barnes  31   32 , John W Eikelboom  33 , Ido Weinberg  6   34 , Sam Schulman  35   36   37 , Marc Carrier  38 , Gregory Piazza  6   39 , Joshua A Beckman  40 , Martin B Leon  1   3 , Gregg W Stone  3   41 , Stephan Rosenkranz  42 , Samuel Z Goldhaber  6   39 , Sahil A Parikh  1   3 , Manuel Monreal  43 , Harlan M Krumholz  2   44   45 , Stavros V Konstantinides  46 , Jeffrey I Weitz  36   37 , Gregory Y H Lip  12   47 ; Global COVID-19 Thrombosis Collaborative Group
Affiliations
Review

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

Behnood Bikdeli et al. Thromb Haemost. 2020 Jul.

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.

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Conflict of interest statement

No specific funding was sought or received for this manuscript. A list of Disclosures for co-authors is available online in the Supplementary Material (available in the online version).

Figures

Fig. 1
Fig. 1
Postulated mechanism of novel treatment options for management of thrombosis in COVID-19. ( A ) Viral alveolar injury and inflammation, including fibrin deposition. ( B ) Viral entry into the endothelial cells and the possible protective effect of hydroxychloroquine. ( C ) Potential mechanism of effect of various agents with antithrombotic properties for mitigating thrombotic complications in COVID-19. COVID-19, coronavirus disease 2019; tPA, tissue-type plasminogen activator.
Fig. 2
Fig. 2
Bar graph representing the research priorities as voted by the coauthors.
Fig. 3
Fig. 3
Considerations for research investigations of pharmacotherapy for prevention of thrombosis or disease progression in patients with SARS-CoV-2 infection.
Fig. 4
Fig. 4
Graphical summary of drug–drug interactions between coronavirus disease 2019 (COVD-19) investigational therapies and antithrombotic agents.
See this image and copyright information in PMC

References

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