- Platelets leads to formation of thrombus
- Alveolar capillaries were found to have thrombi rich in fibrin; neutrophils were also present
- Microthrombi also presented in the capillaries of the lungs
- New platelets have more granules, resulting in the formation of more thrombin
- Platelets activate cytokines that cause inflammation (IL-1beta)
- Platelets cause neutrophils to produce NETs (results in inflammation and coagulation)


Platelets and thrombin’s association with COVID-19


- Neutrophils (which cause inflammation) were found in the capillary thrombi of COVID-19 ALI patients 
- Platelets → neutrophils → NETs
- NETs cause endothelial tissue damage and prevents the destruction of fibrin, resulting in thrombogenesis
- Macrophages that are found in fibrin clots form plasmin
- Plasmin breaks down the fibrin and form D-dimer
- Increased levels of D-dimer are found in those with COVID-19


Neutrophils and macrophages’ association with COVID-19


- Initiated when factor XII binds to PolyP on platelets
- Leads to the formation of thrombi
- Those with COVID-19 have low levels of factor XII; this is due to the overuse of factor XII by the contact pathway
- If the contact pathway is not regulated properly, then thromboinflammation will result


Contact pathway activation in association with COVID-19


- Heparin inhibits the activity of factor X, which forms thrombin
- Study in Wuhan showed that the use of heparin increased the survival rate of COVID-19 patients
- Heparin has a strong anticoagulant effect
- Heparin reduced inflammation in lung tissue (less IL-6 action -- a cytokine)
- Heparin prevents “attacks” from NETs and cytokines, thus reducing inflammation
- Heparin interacts with the spike proteins on the SARS-CoV-2 virus, changing the way the virus interacts with endothelial tissue


Heparin in association with COVID-19


- Those with COVID-19  ALI had increased thrombin activity in the pulmonary capillaries
- Severe COVID-19 patients have increased levels of TAT, also known as thrombin antithrombin complexes
- Thrombin is associated with the coagulation cascade, which results in blood clots (fibrin is formed into fibrinogen)
- Thrombin also increases platelet activity, which results in inflammation
- Thrombin causes inflammation by having P-selection to be expressed
- When thrombin causes WBCs to take action, cytokines are released, also resulting in inflammation


Michigan State University

Thrombosis is involved in immune system functioning. An example of this would be the role platelets play. Platelets bind to the pathogen, thus removing them from circulating in the blood. It also allows serotonin to be secreted, bringing T-cells and neutrophils into play. In those with covid-19, thrombosis, along with inflammation, was present. A group of white blood cells was found around small vessels that contained blood clots and neutrophils. These blood clots are a result of thrombosis and the surrounding white blood cells resulted in inflammation. These factors come together to be known as thromboinflammation.

An overview of thromboinflammation

Mitchell, William. (2020). Thromboinflammation in COVID-19 acute lung injury. Paediatric Respiratory Reviews. 10.1016/j.prrv.2020.06.004. 

URL: https://www.sciencedirect.com/science/article/pii/S1526054220300890?via%3Dihub

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