- 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


Michigan State University

- 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


Thromboinflammation and its relation to COVID-19

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

Thromboinflammation in COVID-19 acute lung injury

- 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


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


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