Thromboinflammation in COVID-19 acute lung injury

William Beau Mitchell, William Beau Mitchell

Abstract

Since the initial description in 2019, the novel coronavirus SARS-Cov-2 infection (COVID-19) pandemic has swept the globe. The most severe form of the disease presents with fever and shortness of breath, which rapidly deteriorates to respiratory failure and acute lung injury (ALI). COVID-19 also presents with a severe coagulopathy with a high rate of venous thromboembiolism. In addition, autopsy studies have revealed co-localized thrombosis and inflammation, which is the signature of thromboinflammation, within the pulmonary capillary vasculature. While the majority of published data is on adult patients, there are parallels to pediatric patients. In our experience as a COVID-19 epicenter, children and young adults do develop both the coagulopathy and the ALI of COVID-19. This review will discuss COVID-19 ALI from a hematological perspective with discussion of the distinct aspects of coagulation that are apparent in COVID-19. Current and potential interventions targeting the multiple thromboinflammatory mechanisms will be discussed.

Keywords: Acute lung injury; COVID-19; Inflammation; Thrombosis.

Copyright © 2020 Elsevier Ltd. All rights reserved.

References

    1. Iba T, Levy JH, Marcel Connors, Jean Marie Thachil, Jecko. Coagulopathy of Coronavirus Disease 2019. Crit Care Med. 2020.
    1. Castagnoli R., Votto M., Licari A. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatrics. 2020
    1. Parri N., Lenge M., Buonsenso D. Children with covid-19 in pediatric emergency departments in Italy. N Engl J Med. 2020
    1. Chao JY, Derespina KR, Herold BC, et al. Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 (COVID-19) at a Tertiary Care Medical Center in New York City. J Pediatrics
    1. Fox SE, Akmatbekov A, Harbert JL, Li G, Brown JQ, Vander Heide RS. Pulmonary and cardiac pathology in Covid-19: the first autopsy series from New Orleans. medRxiv. 2020:2020.2004.2006.20050575.
    1. Varga Z., Flammer A.J., Steiger P. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417–1418.
    1. Ackermann M., Verleden S.E., Kuehnel M. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020
    1. Barton L.M., Duval E.J., Stroberg E., Ghosh S., Mukhopadhyay S. COVID-19 Autopsies, Oklahoma, USA. Am J Clin Pathol. 2020;153(6):725–733.
    1. Jackson S.P., Darbousset R., Schoenwaelder S.M. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms. Blood. 2019;133(9):906–918.
    1. Semple J.W., Freedman J. Platelets and innate immunity. Cell Mol Life Sci. 2010;67(4):499–511.
    1. Gaertner F., Ahmad Z., Rosenberger G. Migrating platelets are mechano-scavengers that collect and bundle bacteria. Cell. 2017;171(6):1368–1382.e1323.
    1. Iannacone M. Platelet-mediated modulation of adaptive immunity. Semin Immunol. 2016;28(6):555–560.
    1. Jin X, Duan Y, Bao T, et al. The values of coagulation function in COVID-19 patients. medRxiv. 2020:2020.2004.2025.20077842.
    1. Hoffman M., Monroe D.M., 3rd. A cell-based model of hemostasis. Thromb Haemost. 2001;85(6):958–965.
    1. Posma J.J., Posthuma J.J., Spronk H.M. Coagulation and non-coagulation effects of thrombin. J Thromb Haemost. 2016;14(10):1908–1916.
    1. Negrier C., Shima M., Hoffman M. The central role of thrombin in bleeding disorders. Blood Rev. 2019;38
    1. Tang N., Bai H., Chen X., Gong J., Li D., Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18(5):1094–1099.
    1. Demelo-Rodríguez P., Cervilla-Muñoz E., Ordieres-Ortega L. Incidence of asymptomatic deep vein thrombosis in patients with COVID-19 pneumonia and elevated D-dimer levels. Thromb Res. 2020;192:23–26.
    1. Helms J., Tacquard C., Severac F. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;1–10
    1. Klok F.A., Kruip M., van der Meer N.J.M. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020
    1. Llitjos J.F., Leclerc M., Chochois C. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients. J Thromb Haemost. 2020
    1. Lodigiani C., Iapichino G., Carenzo L. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020;191:9–14.
    1. Lim W., Meade M., Lauzier F. Failure of anticoagulant thromboprophylaxis: risk factors in medical-surgical critically ill patients. Crit Care Med. 2015;43(2):401–410.
    1. Lindemann S., Tolley N.D., Dixon D.A. Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol. 2001;154(3):485–490.
    1. Battinelli E.M., Markens B.A., Italiano J.E., Jr. Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis. Blood. 2011;118(5):1359–1369.
    1. Müller F., Mutch N.J., Schenk W.A. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell. 2009;139(6):1143–1156.
    1. Rossaint J., Margraf A., Zarbock A. Role of platelets in leukocyte recruitment and resolution of inflammation. Front Immunol. 2018;9:2712.
    1. Lisman T. Platelet-neutrophil interactions as drivers of inflammatory and thrombotic disease. Cell Tissue Res. 2018;371(3):567–576.
    1. Caudrillier A., Kessenbrock K., Gilliss B.M. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Invest. 2012;122(7):2661–2671.
    1. Zuo Y., Yalavarthi S., Shi H. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020
    1. Brinkmann V. Neutrophil extracellular traps in the second decade. J Innate Immun. 2018;10(5–6):414–421.
    1. Mukhopadhyay S., Johnson T.A., Duru N. Fibrinolysis and inflammation in venous thrombus resolution. Front Immunol. 2019;10:1348.
    1. Loscalzo J. The macrophage and fibrinolysis. Semin Thromb Hemost. 1996;22(6):503–506.
    1. Maas C., Renné T. Coagulation factor XII in thrombosis and inflammation. Blood. 2018;131(17):1903–1909.
    1. DeLoughery E.P., Olson S.R., Puy C., McCarty O.J.T., Shatzel J.J. The safety and efficacy of novel agents targeting factors XI and XII in early phase human trials. Semin Thromb Hemost. 2019;45(5):502–508.
    1. Chimenti L., Camprubí-Rimblas M., Guillamat-Prats R. Nebulized heparin attenuates pulmonary coagulopathy and inflammation through alveolar macrophages in a rat model of acute lung injury. Thromb Haemost. 2017;117(11):2125–2134.
    1. Mousavi S., Moradi M., Khorshidahmad T., Motamedi M. Anti-inflammatory effects of heparin and its derivatives: a systematic review. Adv Pharmacol Sci. 2015;2015
    1. Young E. The anti-inflammatory effects of heparin and related compounds. Thromb Res. 2008;122(6):743–752.
    1. Mycroft-West C, Su D, Elli S, et al. The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding. bioRxiv. 2020:2020.2002.2029.971093.
    1. Dixon B, Schultz MJ, Hofstra JJ, Campbell DJ, Santamaria JD. Nebulized heparin reduces levels of pulmonary coagulation activation in acute lung injury. In: Crit Care 14.2010:445.
    1. Dixon B., Santamaria J.D., Campbell D.J. A phase 1 trial of nebulised heparin in acute lung injury. Crit Care. 2008;12(3):R64.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj