Coagulation abnormalities in SARS-CoV-2 infection: overexpression tissue factor

Abstract

Among the pathways and mediators that may be dysregulated in COVID-19 infection, there are proinflammatory cytokines, lymphocyte apoptosis, and the coagulation cascade. Venous and arterial thromboembolisms also are frequent in COVID-19 patients with the increased risk of some life-threatening complications such as pulmonary embolism, myocardial infarction, and ischemic stroke. In this regard, overproduction of proinflammatory cytokines such as IL-6, IL-1β, and TNF-α induce cytokine storms, increase the risk of clot formation, platelet activation, and multiorgan failure that may eventually lead to death among these patients. Surface S protein of SARS-CoV-2 binds to its target transmembrane receptor, named as angiotensin converting enzyme 2 (ACE2(, on various cells such as lymphocyte, alveolar cells, monocytes/macrophages, and platelets. Notably, the activation of the coagulation cascade occurs through tissue factor (TF)/FVIIa-initiated hemostasis. Accordingly, TF plays the major role in the activation of coagulation system during viral infection. In viral infections, the related coagulopathy multiple factors such as inflammatory cytokines and viral specific TLRs are involved, which consequently induce TF expression aberrantly. SARS-COV-2 may directly infect monocytes/ macrophages. In addition, TF expression/release from these cells may play a critical role in the development of COVID-19 coagulopathy. In this regard, the use of TF- VIIa complex inhibitor may reduce the cytokine storm and mortality among COVID-19 patients.

Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms

“…For example, Adams et al (2019) showed that P. gingivalis and bacteria translocated into blood can drive hypercoagulation. However, SARS-CoV-2 also secretes products/proteins that modulate blood clotting cascades ( Eslamifar et al, 2020 ). Pretorius et al (2020a , b , 2021) identified fibrinolytic resistant amyloid microclots in COVID-19 plasma ( Figure 4 ) and in plasma samples collected from 11 PASC subjects.…”

Drug Repurposing and Polypharmacology to Fight SARS-CoV-2 Through Inhibition of the Main Protease

“…SARS-CoV-2 infection often has dramatic consequences for the circulatory system ( Tang et al, 2020b ), with preliminary reports including thrombocytopenia, elevated d-dimer levels, prolonged prothrombin time, and disseminated intravascular coagulation ( Han et al, 2020 ). Interestingly, research findings suggest that inhibition of TF-FVIIa complex may reduce the cytokine storm responsible for the increased coagulation and multi-organ failure, and thus the mortality rate in COVID-19 patients ( Geisbert et al, 2003 ; Eslamifar et al, 2020 ). Our in silico findings suggested that DB04758 could also bind with high affinity to the SARS-CoV-2 M pro .…”

Thromboplasminflammation in COVID-19 Coagulopathy: Three Viewpoints for Diagnostic and Therapeutic Strategies

“…In severe COVID-19 patients, increased platelet activation with P-selectin expression and aIIb/b3 signaling gave rise to platelet aggregation with monocytes followed by increased tissue factor expression on monocytes (118). Moreover, D-dimer levels showed significant correlations with platelet activation for P-selectin and monocyte tissue factor expression (118), which indicate that platelet activation-induced tissue factor expression on monocytes is associated with COVID-19 coagulopathy, leading to DIC in critical cases (10,119).…”