PMID- 35602246 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2688-6146 (Electronic) IS - 2688-6146 (Linking) VI - 3 IP - 2 DP - 2022 May TI - Fibrin clot characteristics and anticoagulant response in a SARS-CoV-2-infected endothelial model. PG - 326-334 LID - 10.1002/jha2.407 [doi] AB - 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. CI - (c) 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd. FAU - McCafferty, Conor AU - McCafferty C AD - Department of Paediatrics The University of Melbourne Melbourne Victoria Australia. AD - Haematology Murdoch Children's Research Institute Melbourne Victoria Australia. FAU - Lee, Leo AU - Lee L AD - Department of Microbiology and Immunology The Peter Doherty Institute for Infection and Immunity The University of Melbourne Melbourne Victoria Australia. FAU - Cai, Tengyi AU - Cai T AD - Department of Paediatrics The University of Melbourne Melbourne Victoria Australia. AD - Haematology Murdoch Children's Research Institute Melbourne Victoria Australia. FAU - Praporski, Slavica AU - Praporski S AD - Haematology Murdoch Children's Research Institute Melbourne Victoria Australia. FAU - Stolper, Julian AU - Stolper J AD - Heart Regeneration Murdoch Children's Research Institute Melbourne Victoria Australia. FAU - Karlaftis, Vasiliki AU - Karlaftis V AD - Haematology Murdoch Children's Research Institute Melbourne Victoria Australia. FAU - Attard, Chantal AU - Attard C AD - Department of Paediatrics The University of Melbourne Melbourne Victoria Australia. AD - Haematology Murdoch Children's Research Institute Melbourne Victoria Australia. FAU - Myint, David AU - Myint D AD - TA Scientific Pty. Ltd. Taren Point Sydney New South Wales Australia. FAU - Carey, Leeanne M AU - Carey LM AD - Department of Occupational Therapy Social Work and Social Policy La Trobe University Melbourne Victoria Australia. AD - Neurorehabilitation and Recovery Florey Institute of Neuroscience and Mental Health University of Melbourne Melbourne Victoria Australia. FAU - Howells, David W AU - Howells DW AD - Tasmanian School of Medicine University of Tasmania Hobart Tasmania Australia. FAU - Donnan, Geoffrey A AU - Donnan GA AD - Melbourne Brain Centre Royal Melbourne Hospital and University of Melbourne Melbourne Victoria Australia. FAU - Davis, Stephen AU - Davis S AD - Melbourne Brain Centre Royal Melbourne Hospital and University of Melbourne Melbourne Victoria Australia. FAU - Ma, Henry AU - Ma H AD - Department of Neurology and Stroke Monash Health Hospital Melbourne Victoria Australia. FAU - Crewther, Sheila AU - Crewther S AD - Department of Psychology and Counselling La Trobe University Melbourne Victoria Australia. FAU - Nguyen, Vinh A AU - Nguyen VA AD - Department of Psychology and Counselling La Trobe University Melbourne Victoria Australia. FAU - Van Den Helm, Suelyn AU - Van Den Helm S AD - Haematology Murdoch Children's Research Institute Melbourne Victoria Australia. FAU - Letunica, Natasha AU - Letunica N AD - Haematology Murdoch Children's Research Institute Melbourne Victoria Australia. FAU - Swaney, Ella AU - Swaney E AD - Department of Paediatrics The University of Melbourne Melbourne Victoria Australia. AD - Haematology Murdoch Children's Research Institute Melbourne Victoria Australia. FAU - Elliott, David AU - Elliott D AD - Heart Regeneration Murdoch Children's Research Institute Melbourne Victoria Australia. FAU - Subbarao, Kanta AU - Subbarao K AD - Department of Microbiology and Immunology The Peter Doherty Institute for Infection and Immunity The University of Melbourne Melbourne Victoria Australia. AD - WHO Collaborating Centre for Reference and Research on Influenza The Peter Doherty Institute for Infection and Immunity Melbourne Victoria Australia. FAU - Ignjatovic, Vera AU - Ignjatovic V AD - Department of Paediatrics The University of Melbourne Melbourne Victoria Australia. AD - Haematology Murdoch Children's Research Institute Melbourne Victoria Australia. FAU - Monagle, Paul AU - Monagle P AD - Department of Paediatrics The University of Melbourne Melbourne Victoria Australia. AD - Haematology Murdoch Children's Research Institute Melbourne Victoria Australia. AD - Department of Clinical Haematology The Royal Children's Hospital Melbourne Victoria Australia. AD - Kids Cancer Centre Sydney Children's Hospital Randwick New South Wales Australia. LA - eng PT - Journal Article DEP - 20220322 PL - United States TA - EJHaem JT - EJHaem JID - 101761942 PMC - PMC9110985 OTO - NOTNLM OT - anticoagulation OT - blood coagulation OT - cell culture OT - electron microscopy OT - viruses COIS- The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. EDAT- 2022/05/24 06:00 MHDA- 2022/05/24 06:01 PMCR- 2022/03/22 CRDT- 2022/05/23 04:23 PHST- 2022/01/10 00:00 [received] PHST- 2022/02/16 00:00 [revised] PHST- 2022/02/18 00:00 [accepted] PHST- 2022/05/24 06:00 [pubmed] PHST- 2022/05/24 06:01 [medline] PHST- 2022/05/23 04:23 [entrez] PHST- 2022/03/22 00:00 [pmc-release] AID - JHA2407 [pii] AID - 10.1002/jha2.407 [doi] PST - epublish SO - EJHaem. 2022 Mar 22;3(2):326-334. doi: 10.1002/jha2.407. eCollection 2022 May.