| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T131 |
0-112 |
Sentence |
denotes |
The canonical role of thrombin is the enzymatic cleavage of fibrinogen to fibrin to ensure efficient hemostasis. |
| T132 |
113-238 |
Sentence |
denotes |
However, thrombin also exerts pleiotropic proinflammatory effects on endothelial cells, platelets, and leukocytes (Figure 3). |
| T133 |
239-372 |
Sentence |
denotes |
In the context of viral infection, the coagulation cascade is activated as a host defence mechanism to try and limit pathogen spread. |
| T134 |
373-925 |
Sentence |
denotes |
Indeed, a number of viruses have been demonstrated to directly activate coagulation, including HIV, Ebola, Coxsackie virus, and Dengue.127 Previous data have highlighted that a major mechanism by which viral infection can induce a procoagulant phenotype pertains to the upregulation of TF expression by virus-infected endothelial cells and endothelial TLR-3 signaling in response to virus-derived pathogen-associated molecular patterns.128,129 However, excessive activation of coagulation and thrombin generation can result in deleterious consequences. |
| T135 |
926-1195 |
Sentence |
denotes |
Thrombin also signals via the PARs, which are widely distributed on a broad range of cells, including platelets, epithelial cells, immune cells, astrocytes, and neurons.130 There are 4 members of the PAR receptors, PAR 1–4, all of which are G protein-coupled receptors. |
| T136 |
1196-1557 |
Sentence |
denotes |
Thrombin efficiently cleaves and activates PAR-1, -3, and -4.131,132 Thus, in addition to being a potent platelet agonist, thrombin also activates immune effector and endothelial cells.133,134 Indeed, thrombin-induced activation of leukocytes results in the production of several cytokines and growth factors while also upregulating leukocyte adhesive function. |
| T137 |
1558-2395 |
Sentence |
denotes |
Thrombin-induced endothelial activation, via PAR-1, induces the production of a range of proinflammatory cytokines and chemokines, including IL-6, IL-8, PAF (platelet-activating factor), and MCP-1, while also triggering the expression of the proadhesive molecules ICAM-1, E- and P-selectin.133–135 Accordingly, PAR signaling has been demonstrated to modulate the immune response to a number of viruses.127 In this regard, the inhibition of coagulation with an FVIIa/TF nematode anticoagulant protein in a model of Ebola virus reduced D-dimer levels, intravascular thrombosis, IL-6, and MCP-1 concentrations and improved survival in treated animals.136 Therefore, the disruption of the normal regulatory mechanisms governing thrombin production and activity occurs in the face of viral sepsis and the ensuing thromboinflammatory response. |
| T138 |
2396-2617 |
Sentence |
denotes |
Thus, given the raised D-dimer levels observed in patients with severe COVID-19, it is likely that dysregulation of the thrombin production is a feature of the prothrombotic phenotype associated with SARS-CoV-2 infection. |
