Fibrin clot characteristics and anticoagulant response in a SARS-CoV-2-infected endothelial model

eJHaem

article

Conor McCafferty¹  Leo Lee³  Tengyi Cai¹  Slavica Praporski²  Julian Stolper⁴  Vasiliki Karlaftis²  Chantal Attard¹  David Myint⁵  Leeanne M. Carey⁶  David W. Howells⁸  Geoffrey A. Donnan⁹  Stephen Davis⁹  Henry Ma^1,10  Sheila Crewther^1,11  Vinh A. Nguyen^1,11  Suelyn Van Den Helm²  Natasha Letunica²  Ella Swaney¹  David Elliott⁴  Kanta Subbarao³  Vera Ignjatovic¹  Paul Monagle¹ 

[1]Department of Paediatrics, The University of Melbourne

[2]Haematology, Murdoch Children's Research Institute

[3]Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne

[4]Heart Regeneration, Murdoch Children's Research Institute

[5]TA Scientific Pty. Ltd. Taren Point

[6]Department of Occupational Therapy, Social Work and Social Policy, La Trobe University

[7]Neurorehabilitation and Recovery, Florey Institute of Neuroscience and Mental Health, University of Melbourne

[8]Tasmanian School of Medicine, University of Tasmania

[9]Melbourne Brain Centre, Royal Melbourne Hospital and University of Melbourne

[10]Department of Neurology and Stroke, Monash Health Hospital

[11]Department of Psychology and Counselling, La Trobe University

[12]WHO Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity

[13]Department of Clinical Haematology, The Royal Children's Hospital

[14]Kids Cancer Centre, Sydney Children's Hospital

关键词: anticoagulation;    blood coagulation;    cell culture;    electron microscopy;    viruses;   

DOI  :  10.1002/jha2.407

来源: Wiley

【 摘 要 】

Coronavirus disease 2019 (COVID-19) patients have increased thrombosis risk. With increasing age, there is an increase in COVID-19 severity. Additionally, adults with a history of vasculopathy have the highest thrombotic risk in COVID-19. The mechanisms of these clinical differences in risk remain unclear. Human umbilical vein endothelial cells (HUVECs) were infected with SARS-CoV-2, influenza A/Singapore/6/86 (H1N1) or mock-infected prior to incubation with plasma from healthy children, healthy adults or vasculopathic adults. Fibrin on surface of cells was observed using scanning electron microscopy, and fibrin characteristics were quantified. This experiment was repeated in the presence of bivalirudin, defibrotide, low-molecular-weight-heparin (LMWH) and unfractionated heparin (UFH). Fibrin formed on SARS-CoV-2 infected HUVECs was densely packed and contained more fibrin compared to mock-infected cells. Fibrin generated from child plasma was the thicker than fibrin generated in vasculopathic adult plasma ( p  = 0.0165). Clot formation was inhibited by LMWH (0.5 U/ml) and UFH (0.1–0.7 U/ml). We show that in the context of the SARS-CoV-2 infection on an endothelial culture, plasma from vasculopathic adults produces fibrin clots with thinner fibrin, indicating that the plasma coagulation system may play a role in determining the thrombotic outcome of SARS-CoV-2 infection. Heparinoid anticoagulants were most effective at preventing clot formation.

【 授权许可】

Unknown