COVID-19 Thrombosis: Bridging the Old and New Concepts

Abstract

The coronavirus disease 2019 (COVID-19) pandemic is an evolving condition in the absence of established treatment and vaccines. The few autopsy studies on COVID-19 patients suggested the presence of pulmonary microvascular thrombosis. Hence, it is imperative to understand the pathobiology of thrombus formation and speculate the therapeutic goals in combating COVID-19. This paper focuses on a holistic approach by integrating the previous concepts and current concepts of thrombosis to better understand the pathogenesis of thrombosis.

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

“…In a meta-analysis of 102 studies involving 64,503 patients with COVID-19, the incidence of venous thromboembolism was 14.7% (95% CI 12.1-17.6%), while the rate of arterial thrombotic events was 3.9% (95% CI 2.0-3.0) [37]. According to other studies, the rate of venous thromboembolism varies from 25% to 69% [38]. Among hospitalized COVID-19 patients, a high incidence of alterations in inflammatory and coagulation biomarkers also correlates with a poor prognosis [39].…”

“…The rise in the incidence of thrombosis in large and small vessels can be explained by the presence of multiple factors, namely, the stasis of flow due to prolonged bed immobilization, vessel wall damage secondary to the loss of the normal thromboprotective state of the endothelium (due to inflammation and irritation caused by central venous catheters), hypercoagulable state caused by sepsis and endothelial activation due to the virus itself, thrombophilic inflammation responsible for the increase of von Willebrand factor and factor VIII, and neutrophil/platelet activation [41,42]. Venous thromboembolism is further favored by the hemodynamic effects of prolonged mechanical ventilation [38].…”

“…It has been hypothesized that SARS-CoV-2 infection induces an immuno-thrombosis, in which neutrophils and activated monocytes interact with platelets and the coagulation cascade [38,47]. 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.…”

“…A meta-analysis showed that most severe cases of COVID-19 show a significant decrease in platelet counts (up to about 10,000) [46]. The pathogenesis of thrombocytopenia is probably related to the platelets' overactivation by the complement through the generation of procoagulant microparticles and the insertion of C5b-9 in lytic quantities on platelets, in the absence of complement regulators [38]. Activated platelets also express a functionally active tissue factor (TF) that can trigger the coagulation cascade [54].…”

“…The cascade of the uncontrolled multiplication of cytokines TNF-α, IL-1, and IL-6 present in patients with severe COVID-19, induced by complement and activated platelets, can also lead to a disseminated intravascular coagulation syndrome (DIC) [28,34,35,38]. In a meta-analysis of 14 studies, the incidence of DIC was 3% (95% CI: 1-5%, p < 0.001) and affected patients showed higher mortality (OR = 2.46, 95% CI: 0.94-3.99, p < 0.001) [55].…”