Prothrombotic Phenotype in COVID-19: Focus on Platelets

Abstract

COVID-19 infection is associated with a broad spectrum of presentations, but alveolar capillary microthrombi have been described as a common finding in COVID-19 patients, appearing as a consequence of a severe endothelial injury with endothelial cell membrane disruption. These observations clearly point to the identification of a COVID-19-associated coagulopathy, which may contribute to thrombosis, multi-organ damage, and cause of severity and fatality. One significant finding that emerges in prothrombotic abnormalities observed in COVID-19 patients is that the coagulation alterations are mainly mediated by the activation of platelets and intrinsically related to viral-mediated endothelial inflammation. Beyond the well-known role in hemostasis, the ability of platelets to also release various potent cytokines and chemokines has elevated these small cells from simple cell fragments to crucial modulators in the blood, including their inflammatory functions, that have a large influence on the immune response during infectious disease. Indeed, platelets are involved in the pathogenesis of acute lung injury also by promoting NET formation and affecting vascular permeability. Specifically, the deposition by activated platelets of the chemokine platelet factor 4 at sites of inflammation promotes adhesion of neutrophils on endothelial cells and thrombogenesis, and it seems deeply involved in the phenomenon of vaccine-induced thrombocytopenia and thrombosis. Importantly, the hyperactivated platelet phenotype along with evidence of cytokine storm, high levels of P-selectin, D-dimer, and, on the other hand, decreased levels of fibrinogen, von Willebrand factor, and thrombocytopenia may be considered suitable biomarkers that distinguish the late stage of COVID-19 progression in critically ill patients.

Platelet-to-Lymphocyte Ratio (PLR) Is Not a Predicting Marker of Severity but of Mortality in COVID-19 Patients Admitted to the Emergency Department: A Retrospective Multicenter Study

“…Lymphopenia could be linked to a cell-exhaustion phenomenon, direct viral lymphocyte infection, bone marrow infection, apoptosis of lymphocytes led by inflammation and inhibition of lymphocytes by metabolic dysregulation [ 29 , 30 ]. Thrombocytopenia is essentially linked to platelet consumption, but also to lower levels of production due to bone marrow damage and to an immunological phenomena leading to platelet destruction [ 31 ]. However, since those do not appear from the same mechanism, the onset speed of these two biological anomalies differs.…”

SCUBE1 is associated with thrombotic complications, disease severity, and in-hospital mortality in COVID-19 patients

“…This glycoprotein is secreted and surface-exposed on activated platelets, promotes platelet-platelet interaction and promotes platelet-matrix adhesion and agglutination and therefore, increased plasma level of SCUBE1 is used as a biomarker of platelet activation in acute thrombotic diseases [26] , [27] . Clinical studies have shown significantly higher plasma SCUBE1 levels in acute thrombotic complication processes such as acute coronary syndrome, acute ischemic stroke, high thrombus load in patients presenting with STEMI, and the no-reflow phenomenon after stent implantation [28] , [29] , [30] . In the experimental study by Wu et al, they showed that plasma SCUBE1 is not only a biomarker in acute thrombotic processes, but also plays an active role in the thrombosis process [8] .…”

COVID-19, Vaccines, and Thrombotic Events: A Narrative Review

“…The main activation of the signal pathways to produce inflammatory cytokines are the toll-like receptors that recognize the presence of viral nucleic acids and the ACE-2 receptors, which the virus uses to infect cells. The coagulation alterations are mainly mediated by the activation of platelets [48]. The procoagulating effect of hypoxia should also be considered.…”