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Experimental and Imaging Techniques for Examining Fibrin Clot Structures in Normal and Diseased States
Published on: April 1, 2015
Fibrin clot characteristics and anticoagulant response in a SARS-CoV-2-infected endothelial model
Conor McCafferty1,2, Leo Lee3, Tengyi Cai1,2
1Department of Paediatrics The University of Melbourne Melbourne Victoria Australia.
Insights
COVID-19 increases thrombosis risk, especially in older adults and those with vasculopathy. SARS-CoV-2 infection on endothelial cells showed plasma from vasculopathic adults formed thinner fibrin clots, suggesting a role for coagulation factors.
Area of Science:
- Endothelial biology
- Virology
- Hematology
Background:
- Coronavirus disease 2019 (COVID-19) is associated with increased thrombosis risk, particularly in older individuals and those with pre-existing vasculopathy.
- The underlying mechanisms contributing to these varying thrombotic risks in COVID-19 patients remain incompletely understood.
- Endothelial dysfunction is a key feature in severe COVID-19, potentially influencing coagulation pathways.
Purpose of the Study:
- To investigate the role of endothelial cells and plasma characteristics in COVID-19-associated thrombosis.
- To compare fibrin clot formation on SARS-CoV-2 infected endothelial cells using plasma from different age groups and individuals with vasculopathy.
- To evaluate the efficacy of anticoagulants in mitigating clot formation in this in vitro model.
Main Methods:
- Human umbilical vein endothelial cells (HUVECs) were infected with SARS-CoV-2 or influenza A, or mock-infected.
- Infected HUVECs were incubated with plasma from healthy children, healthy adults, or adults with vasculopathy.
- Fibrin formation was analyzed using scanning electron microscopy and quantified; experiments were repeated with anticoagulants (bivalirudin, defibrotide, LMWH, UFH).
Main Results:
- SARS-CoV-2 infection of HUVECs resulted in denser fibrin formation compared to mock-infected cells.
- Plasma from healthy children generated thicker fibrin clots than plasma from vasculopathic adults (p=0.0165).
- Low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) effectively inhibited clot formation.
Conclusions:
- SARS-CoV-2 infection on endothelial cells, when combined with plasma from vasculopathic adults, leads to thinner fibrin clots, implicating the plasma coagulation system in COVID-19 thrombotic outcomes.
- The study highlights distinct fibrin characteristics based on plasma source, suggesting individual coagulation profiles influence thrombotic risk in COVID-19.
- Heparinoid anticoagulants demonstrated significant efficacy in preventing in vitro clot formation, offering potential therapeutic insights for managing COVID-19-related coagulopathy.
Abstract:
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.
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